Faculty of Arts, Charles University in Prague, Department of Psychology Richard Lukáš Psychology students' attitudes towards adoption of children by same-sex couples (Master Thesis) Consultant: PhDr. Lenka Krejčová, Ph.D. Praha 2018 Abstract: Same-sex parenting (homoparentality) is new, yet still not well explored phenomena in Czech Republic. Purpose of this study is to explore the attitudes of Czech psychology students (N=337) to homoparentality. The vignettes, i.e. model stories describing the situation of a couple preparing to adopt a child, were used. The sexual orientation of the couple and child's gender varied. After reading one of the six versions of the vignette, participants assessed the parental competences and child's future development after adoption. The factor analysis of dependent variables was performed with 8 scales as a result. Independent variables were traditional and modern homophobia, beliefs about etiology of homosexuality, gender roles attitudes etc. Results indicate that students view homoparentality rather positively. However, the homoparental and heteroparental families were rated differently. The participants were more concerned about normative sexual development and victimization of children from homoparental families. On the other hand, children from heteroparental families...

Hintergrund. Angst- und depressive Störungen treten sehr häufig auf. Die Komorbidität zwischen beiden Störungsgruppen ist hoch. Quer- und Längsschnittstudien legen nahe, dass vorausgehende Angststörungen das Risiko sekundärer Depression erhöhen, wobei wenig zur Rolle klinischer Charakteristika von Angststörungen in diesem Zusammenhang bekannt ist. Es liegen eine Fülle von Befunden zu Risikofaktoren für Angst- und depressive Störungen vor, die bei genauerer Betrachtung allerdings eine Reihe methodischer Limitationen und offener Forschungsfragen aufweisen (z.B. viele Querschnittserhebungen, klinische Stichproben, keine vergleichenden Analysen der Risikofaktoren von Angststörungen versus Depression). Eine reliable Bewertung der diagnostischen Spezifität vs. Unspezifität von Vulnerabilitäts- und Risikofaktoren von Angst- und depressiven Störungen mit den bislang vorliegenden Ergebnissen schwer möglich ist. Fragestellungen. Es wurden Gemeinsamkeiten und Unterschieden hinsichtlich der Korrelate und Risikofaktoren von reinen Angst- versus reinen depressiven Störungen untersucht. Durch einen Vergleich reiner Angst- mit reinen depressiven Störungen sollte eine reliablere Einschätzung der Spezifität versus Unspezifität der untersuchten Vulnerabilitäts- und Risikofaktoren erfolgen. Der zweite Fokus lag in der Analyse der Rolle von primären Angststörungen und der mit ihnen assoziierten klinischen Merkmale bei der Entwicklung sekundärer Depressionen. Methoden. Die „Early Developmental Stages of Psychopathology (EDSP)“- Studie ist eine prospektive, longitudinale Studie. Eine repräsentative Bevölkerungsstichprobe von ursprünglich 3021 Jugendlichen und jungen Erwachsenen (zu Baseline 14-24 Jahre alt) wurde dreimal befragt (eine Baseline-Erhebung sowie zwei Folgebefragungen). Zusätzlich wurden die Eltern der Probanden, die am ersten Follow-Up teilgenommen hatten, in einem Elterninterview direkt interviewt. Von 2548 Probanden lagen diagnostische Informationen von der Basisbefragung und des Follow-Up-Zeitraumes vor. Psychische Störungen wurden mit Hilfe des M-CIDI nach DSM-IV Kriterien erfasst. Darüber hinaus wurden eine Vielzahl potenzieller Risikofaktoren (z.B. Behavioral Inhibition, kritische Lebensereignisse) erhoben. Ergebnisse. Die drei wichtigsten Ergebnisse dieser Arbeit waren: a)Es konnten gemeinsame, aber auch einige spezifische Risikofaktoren für Angststörungen versus depressive Störungen nachgewiesen werden. b)Die Angststörungen stellen eine heterogene Gruppe dar: Auch innerhalb der Gruppe der Angststörungen zeichnen sich spezifische Risikofaktoren für spezifische Angststörungen ab (d.h. es fanden sich Unterschiede zwischen Spezifischer und Sozialer Phobie). c)Es wurden starke Assoziationen zwischen Angststörungen sowie der mit ihnen assoziierten Merkmale (Beeinträchtigung, Komorbidität, Panikattacken) und der Entwicklung sekundärer depressiver Störungen gefunden. Im multiplen Modell, das alle klinischen Merkmale beinhaltete, stellte sich der Faktor schwere Beeinträchtigung als bedeutendster Prädiktor heraus. Diskussion und Schlussfolgerungen. Insgesamt befürworten die Befunde dieser Arbeit eher die sog. Splitters-Perspektive von zumindest teilweise unterschiedlichen Risikofaktoren für Angst- und depressive Störungen. Einer der potentesten Risikofaktoren für depressive Störungen scheinen vorausgehende Angststörungen zu sein, der Schweregrad der Beeinträchtigung durch die Angststörung spielt dabei eine entscheidende Rolle. Eine rechtzeitige, effektive Behandlung dieser Angststörungen könnte eine sehr erfolgversprechende Strategie in der Prävention depressiver Störungen sein. Der Beeinträchtigungsgrad durch die Angststörung kann dabei zur Identifizierung von sog. Hoch-Risiko-Personen genutzt werden. / Background. Anxiety disorders and depression are frequent mental disorders; comorbidity is high. Although cross-sectional and longitudinal studies suggest that anxiety disorders increase the risk of subsequent depression, little is known about the role of clinical characteristics of anxiety disorder in this association. Furthermore, there are a lot of studies investigating risk factors of anxiety disorders and depression. Most of these studies, however, have some substantial limitations (e.g., cross-sectional design, clinical samples, lack of analyses comparing risk factors of anxiety disorders versus depression) preventing a reliable assessment of the specificity of vulnerability and risk factors for anxiety disorders and depression. Aims. The first aim of the study was to examine common and specific correlates and risk factors of pure anxiety disorders versus pure depression. The second aim was to analyse the association between anxiety disorders and subsequent depression and the role of clinical characteristics of anxiety disorders in this associations. Methods. The data are from the Munich Early Developmental Stages of Psychopathology (EDSP) study. The EDSP study is a 4-year prospective-longitudinal community study, which includes both baseline and follow-up data on 2548 adolescents and young adults 14 to 24 years of age at baseline. Parents of those probands participated at the first follow-up of the study were also interviewed. DSM-IV diagnoses were made using the Munich-Composite International Diagnostic Interview (M-CIDI). A range of risk factors were assessed (e.g., behavioral inhibition, life events). Results. There were both common and specific risk factors of anxiety disorders and depression. Furthermore, specific risk factors for specific anxiety disorders could be identified (i.e. different risk factors of specific phobia versus social phobia were found). Anxiety disorders and their clinical characteristics (impairment, comorbidity, panic attacks) were significantly associated with the development of subsequent depression. In the final model, which included all clinical characteristics, severe impairment remained the only clinical feature that was an independent predictor of subsequent depression. Discussion and conclusions. The findings suggest that there are specific risk factors of anxiety disorders and depression. Anxiety disorders are a very powerful risk factor for subsequent depression whereas severe impairment seems to play a major role in this association. Effective treatment of anxiety disorders, specifically those associated with extreme disability, might be important for targeted primary prevention of depression. The degree of impairment of anxiety disorders could be used for the identification of individuals at highest risk for onset of depression.

The consequences of early embryonic insults and how they affect subsequent life reflects the emerging concept of "fetal programming". The aim of this project is to study the effects of embryonic insults as they subsequently manifest themselves in adults, with emphasis on the heart and vasculature. My experiments establish that fetal programming operates on the bobwhite quail inducing similar changes as those observed in mammalians and other birds. The quail's fast development provides reliable data in a short period of time than other avian models (e.g. domestic chicken). Data on quail showed a correlation between egg mass and hatchling mass; where small eggs produce small hatchlings but a high mortality made it impractical as a stressor for this study. Hypoxia was used as a stressor during embryonic incubation, where it induced a low hatching weight in quail that was not observable in adult birds. Morphological measurements demonstrated an increased ventricular collagen content and reduced ventricular lumen in birds in adults incubated in hypoxia consistent with hypertension. The hematological analyzes showed few differences indicating organ remodeling instead of hematopoietic compensation. The assessment of vascular reactivity pointed out an impaired endothelium dependent relaxation commonly associated to hypertension in birds and mammals. Fetal programming could be a widespread response to an adverse prenatal environment in endotherms and the resulting data from this work contributes to our understanding of fetal programming in vertebrates and its long term consequences.

Objective: To determine the prevalence and odds ratios for cleft lip and/or palate (CL/P) among infants prenatally exposed to opioids with or without neonatal opioid withdrawal syndrome (NOWS). Design: This study represents an exploratory, retrospective cohort study design of newborn medical health records from 2011 to 2016. Setting: Records were drawn from a regional health system located in South Central Appalachia. Population and study sample: The original population yielded 3 cohorts of infants: (1) infants with opioid exposure (OE) but not requiring pharmacological intervention (OE; N = 168); (2) infants with NOWS requiring pharmacological intervention (N = 294); and (3) infants with no opioid exposure (NOE; N = 16 090), the primary comparison group. Main outcome: Infants in the NOWS and OE groups showed significantly increased prevalence and odds ratios for CL/P when compared to those in the NOE group. Results: Prevalence rates per 1000 live births for infants with OE (35.71) and infants with NOWS (6.80) were significantly higher than those for infants with NOE (1.37). Comparison of infants with OE to the NOE group revealed significantly increased odds for CL/P, isolated cleft palate (CP), cleft lip (CL), and cleft lip and palate (CLP) (27.05, 41.81, 19.26, 19.37, respectively; all Ps < .008). The odds ratios for infants with NOWS compared to the NOE group were significantly higher for CL/P and CP (5.00 and 10.98, respectively; Ps < .03) but not for CL and CLP. Conclusion: The results provide additional evidence that prenatal OE should be considered among the critical environmental risk factors that can contribute to CL/P.

Indiana University-Purdue University Indianapolis (IUPUI) / Haemophilus ducreyi causes chancroid, a sexually transmitted genital ulcerative disease that facilitates the transmission of HIV-1. H. ducreyi also causes non-sexually transmitted cutaneous ulcers in children in tropical regions. During human infection, H. ducreyi is subject to a variety of stresses. The stringent response is a bacterial stress response system induced by nutrient limiting conditions and mediated by guanosine tetra- and pentaphosphate [(p)ppGpp] and the transcriptional regulator DksA. (p)ppGpp and DksA jointly interact with RNA polymerase to regulate genes critical for bacterial survival. We hypothesized that the stringent response is required for H. ducreyi virulence in humans. A ΔrelAΔspoT mutant, which is unable to synthesize (p)ppGpp, was partially attenuated for abscess formation in human volunteers. Loss of (p)ppGpp increased bacterial resistance to phagocytosis and stationary phase survival; however, the mutant was more sensitive to oxidative stress. A ΔdksA mutant was also partially attenuated in humans. The ΔdksA mutant behaved like the (p)ppGpp mutant in stationary phase survival and sensitivity to oxidative stress, but exhibited decreased resistance to phagocytosis. Both mutants had decreased adherence to fibroblasts, but the mechanisms underlying the adherence defect were distinct. To better understand the roles of (p)ppGpp and DksA in regulating gene expression, we performed transcriptome analysis of the parent and mutant strains. (p)ppGpp and DksA deficiency resulted in dysregulation of multiple genes including several known virulence determinants. At stationary phase, (p)ppGpp and DksA targets were not identical but significantly overlapped; as the mutants were phenotypically distinct, this finding underscores both the unique and joint roles DksA and (p)ppGpp play in regulation of H. ducreyi virulence. We conclude that (p)ppGpp and DksA play significant roles in H. ducreyi pathogenesis. This is the first study to show that the stringent response has a direct role in the ability of a bacterial pathogen to cause disease in humans.

Indiana University-Purdue University Indianapolis (IUPUI) / Pancreatic ductal adenocarcinoma (PDA) is a deadly disease due to early metastasis and resistance to chemotherapy. PDA is commonly associated with a dense desmoplastic stroma, which forms a protective niche for cancer cells. Tissue transglutaminase (TG2), a Ca2+-dependent enzyme, is abundantly expressed in pancreatic cancer cells and crosslinks proteins through acyl-transfer transamidation between glutamine and lysine residues. The objective of the study was to determine the functions of TG2 in the pancreatic stroma. Orthotopic pancreatic xenografts and co-culture systems tested the mechanisms by which the enzyme modulates tumor-stroma interactions. We showed that TG2 secreted by cancer cells is enzymatically active and renders the stroma denser by crosslinking collagen, which in turn activates fibroblasts and stimulates their proliferation. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are transcription factors involved in mechanotransduction. The TG2-mediated fibrosis-rich, stiff microenvironment conveys mechanical cues to cancer cells leading to activation of YAP and TAZ, promoting cell proliferation and tumor growth. Stable knockdown of TG2 in pancreatic cancer cells led to decreased size of pancreatic xenografts and increased sensitivity of xenografts to gemcitabine. Taken together, our results demonstrate that TG2 secreted in the tumor microenvironment orchestrates the crosstalk between cancer cells and the stroma, fundamentally impacting tumor growth and response to chemotherapy. Our study supports TG2 inhibition in the pancreatic stroma as a novel strategy to block pancreatic cancer progression.

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Indiana University-Purdue University Indianapolis (IUPUI) / The first part of the study describes the development of a microCT based engineering model to study orthodontic responses. The second part investigated the relationship between orthodontic stimulus, root resorption and bone modeling. It was hypothesized that stress magnitudes are insufficient to portray the mechanical environment and explain the clinical response; directions also play a role. An idealized tooth model was constructed for finite element analysis. The principal stress magnitudes and directions were calculated in tipping and translation. It was concluded that within the same region of root, PDL and bone, there can be compression in one structure, tension in another. At a given point in a structure, compression and tension can coexist in different directions. Magnitudes of compression or tension are typically different in different directions. Previously published data presenting only stress magnitude plots can be confusing, perhaps impossible to understand and/or correlate with biological responses. To avoid ambiguities, a reference to a principal stress should include its predominant direction. Combined stress magnitude/direction results suggest that the PDL is the initiator of mechanotransduction. The third part of this project tested the role of the P2X7 receptor in the dentoalveolar morphology of C57B/6 mice. P2X7R KO (knockout) mice were compared to C57B/6 WT to identify differences in a maxillary molar and bone. Tooth dimensions were measured and 3D bone morphometry was conducted. No statistically significant differences were found between the two mouse types. P2X7R does not have a major effect on alveolar bone or tooth morphology. The final part examines the role of the P2X7 receptor in a controlled biomechanical model. Orthodontic mechanotransduction was compared in wild-type (WT) and P2X7R knock-out (KO) mice. Using Finite Element Analysis, mouse mechanics were scaled to produce typical human stress levels. Relationships between the biological responses and the calculated stresses were statistically tested and compared. There were direct relationships between certain stress magnitudes and root resorption and bone formation. Hyalinization and root and bone resorption were different in WT and KO. Orthodontic responses are related to the principal stress patterns in the PDL and the P2X7 receptor plays a significant role in their mechanotransduction.

Indiana University-Purdue University Indianapolis (IUPUI) / Potential problems of one-step adhesives have been identified, including water uptake and subsequent plasticization, water-and enzyme-induced nanoleakage, and the presence of voids due to phase-separation or osmosis. Clinically, adhesive failures due to marginal degradation present as retention loss, marginal discoloration, and secondary caries. However, the mechanisms of adhesive interface degradation of self-etching and self-bonding resin luting agents are not fully understood. The objective of the study was to investigate adhesive layer degradation by using a nanoleakage technique with five different resin luting agents. Materials and Methods: Five different resin luting systems, Variolink II, Panavia F2.0, RelyX Unicem, RelyX Unicem2, and Maxcem Elite were evaluated in this study. The 25 dentin specimens were randomly divided into five resin luting agent groups. Flat dentin surfaces were created mid-coronally and were luted with luting agents. Then, each tooth was sectioned occluso-gingivally. The first half of each tooth was used as a control group and the other half was used as the experimental group. The control group was immersed in artificial saliva at 37°C and SEM examination with chemical analysis was performed within 48 hours. In the tested group, all specimens were immersed in artificial saliva at 37°C for 10 days and thermocycled. For the SEM examination, the specimens were immersed in a 50-percent ammoniacal silver nitrate solution for 24 hours.22 SEM was used for observation of silver penetration of the specimens. Three scan lines were selected. For elemental analysis, natural apatite, olivine minerals, and pure silver metal were chosen as standards for Ca, Si and Ag. Data were analyzed using ANOVA with a 5-percent significance level. Results: At the bottom of the hybrid layer, there was no significant difference in silver uptake within the adhesive interface between luting agents (p > 0.05) and there was no significant change in silver uptake within the adhesive interface after thermocycling (aging) (p > 0.05). Conclusion: All resin luting agents exhibited nanoleakage after both 24-hour storage and 10-day storage with thermocycling.