This dissertation reports on an investigation of transition-to-proof students' understanding of proof by contradiction. A plethora of research on the construction aspect of proof by contradiction is available and suggests that the method is one of the most difficult for students to construct and comprehend. However, there is little research on the students' comprehension of proofs and, in particular, proofs by contradiction. This study aims to fill this gap in the literature. Applying the cognitive lens of Action-Process-Object-Schema (APOS) Theory to proof by contradiction, this study proposes a preliminary genetic decomposition for how a student might construct the concept `proof by contradiction' and a series of five teaching interventions based on this preliminary genetic decomposition. Data was analyzed in two ways: (1) group analysis of the first two teaching interventions to consider students' initial conceptions of the proof method and (2) case study analysis of two individuals to consider how students' understanding developed over time. The genetic decomposition and teaching interventions were then revised based on the results of the data analysis. This study concludes with implications for teaching the concept of proof by contradiction and suggestions for further research on the topic.

Peptídeos com ação inibitória sobre a enzima conversora de angiotensina I (ECA) e com o potencial de reduzir a pressão arterial têm sido obtidos a partir de diferentes tipos de alimentos ou matérias-primas, sendo grande o interesse em aproveitar resíduos da indústria alimentícia como fontes desses peptídeos. Neste aspecto, as amêndoas de cupuaçu (Theobroma grandiflorum S.), que são em sua maioria descartadas pela indústria, apresentam um teor considerável de proteínas e poderiam ser aproveitadas como fontes de peptídeos inibidores da ECA. Assim, o objetivo deste trabalho foi verificar se o concentrado proteico obtido a partir de amêndoas fermentadas de cupuaçu após ser submetido à hidrólise com a enzima pepsina poderia gerar peptídeos com ação inibitória sobre a ECA in vitro. Foi observado que após a hidrólise do concentrado proteico com pepsina por 1h foi obtido um efeito de 50 % de inibição da ECA, em ensaio realizado com o substrato Abz-FRK(Dnp)-P-OH. Posteriormente, esse hidrolisado foi submetido ao fracionamento por cromatografia em fase reversa (RP-HPLC) e resultou em cinco frações (F1-F5), das quais a terceira teve uma subfração (F3.1) com quatro novos peptídeos identificados por LC-MS/ MS com potencial em inibir a ECA. Esses quatro peptídeos (FWVAM, YRLAF, LGYFK, VTTVVTGLTF) foram sintetizados e submetidos aos ensaios para a determinação do IC50 e Ki. Os peptídeos YRLAF e LGYFK, que apresentaram mecanismo de inibição do tipo competitivo e acompetitivo, respectivamente, tiveram valores de IC50 de 4.73 e 11.11µM, e de Ki de 9.14 e 8.15 µM. Dentre os peptídeos identificados merece destaque VTTVVTGLTF que demonstrou ser um inibidor do tipo acompetitivo e apresentou as menores IC50 (0.70 µM) e Ki (2.79 µM). Em contraste, FWVAM atuou como substrato da ECA e não peptídeo inibidor. A partir dos resultados obtidos neste estudo fica demonstrado que as amêndoas fermentadas de cupuaçu podem ser fonte de peptídeos com ação inibitória da ECA, com potencial efeito anti-hipertensivo a ser, futuramente, investigado a partir de estudos in vivo. / Angiotensin converting enzyme (ACE) inhibitory peptides with the potential to reduce blood pressure have been obtained from different types of food or raw materials, and there is a great interest in utilize residues from the food industry as sources of peptides. In this regard, cupuassu almonds (Theobroma grandiflorum S.), which are mostly discarded by the industry, has a considerable protein content and could be used as source of ACE-inhibiting peptides. Thus, the objective of this work was to verify if the protein concentrate obtained from fermented almonds of cupuassu after being submitted to the hydrolysis with the enzyme pepsin could generate peptides with inhibitory activity on ACE in vitro. In this study it was observed that after hydrolysis of the protein concentrate with pepsin for 1 h, a 50% effect of ACE inhibition was obtained in an assay performed with the Abz-FRK (Dnp) -P-OH substrate. Posteriorly, the hydrolyzate was subjected to fractionation by reverse phase chromatography (RP-HPLC) and resulted in five fractions (F1-F5), of which the third had a subfraction (F3.1) with four new peptides identified by LC-MS / MS with the potential to inhibit ACE. These four peptides (FWVAM, YRLAF, LGYFK, VTTVVTGLTF) were synthesized and assayed for IC50 and Ki. The YRLAF and LGYFK peptides, which showed a competitive and uncompetitive type inhibition mechanism respectively, presented IC50 values of 4.73 and 11.11µM, and the values for Ki were 9.14 and 8.15 µM. Among the peptides identified, it is possible to highlight VTTVVTGLTF, which was shown to be an inhibitor of the uncompetitive type and presented the lowest value for IC50 (0.70 µM) and Ki (2.79 µM). While FWVAM acted as a substrate of the ACE and not as an inhibitory peptide. From the results obtained in this study it is demonstrated that cupuassu fermented almonds can be a source of peptides with ACE inhibitory activity with potential antihypertensive effect to be further investigated from in vivo studies.

No description available.

Sammanfattning Introduktion: Hypertoni utgör en stor riskfaktor som kraftigt ökar risken att drabbas av kardiovaskulär sjukdom, en av världens ledande dödsorsaker idag. Två av förstahandsvalen vid farmakologisk behandling av hypertoni är Ca2+-antagonister och ACE-hämmare. Ca2+-antagonister ger kärldilatation med effekten sänkt blodtryck genom att få den glatta muskulaturen runt artärer och arterioler att relaxera. ACE-hämmare verkar genom att påverka kroppens renin-angiotensin-aldosteron-system (RAAS) genom att inhibera ett viktigt enzym som deltar i RAAS-processen. Resultatet blir utebliven vasokonstriktion samt minskad Na+-retention, vilket medför blodtryckssänkning. I Sverige bestäms behandlingsplan utefter patientens riskprofil, där en låg risk för kardiovaskulär sjukdom med samtidig mild hypertoni medför initial icke-farmakologisk behandling som övergår i monoterapi vid utebliven effekt, medan högre risk med samtidig måttlig eller svår hypertoni medför initial kombinationsterapi. Syfte och metod: Syftet var att undersöka effektiviteten hos Ca2+-antagonister och ACE-hämmare som monoterapi eller kombinationsterapi vid farmakologisk behandling av primär hypertoni. Examensarbetet utformades som en litteraturstudie för att besvara frågeställningen. Databasen PubMed nyttjades för att finna fem randomiserade och kontrollerade studier som jämförde kombinationsterapi och monoterapi med Ca2+-antagonister och ACE-hämmare. Resultat: Alla fem studier som undersöktes erhöll resultat där kombinationsterapi tenderade att ge en mer effektiv blodtryckssänkning i jämförelse med monoterapi, även om inte alla studier erhöll signifikant större sänkning av blodtryck i jämförelse med monoterapi. Tre av studierna visade en signifikant större reduktion av blodtryck vid kombinationsterapi i jämförelse med monoterapi, medan två av studierna inte visade på en signifikant reduktion. Dock återfanns denna tendens även hos dessa två studier där kombinationsterapi var mer effektiv i att reducera blodtryck. I tre av fem studier uppnådde en större andel patienter från kombinationsgrupperna målblodtrycket (<140/90 mmHg) än i monoterapigrupperna. Gällande biverkningar visade ingen av studierna någon skillnad i biverkningsgrad mellan kombinationsterapi och monoterapi. Slutsatser: Den samlade slutsatsen utifrån de undersökta studierna visar att kombinationsterapi med både Ca2+-antagonister och ACE-hämmare sänker blodtryck mer effektivt än monoterapi med vardera substansen. Eftersom en del av skillnaderna trots allt var små kan den biologiska relevansen av reduktionen diskuteras. Då biverkningarna inte var fler vid kombinationsterapi bör kombinationsterapi i framtiden övervägas som primärval vid behandling av primär hypertoni.

Pregnancy alcohol consumption has been linked to poor birth outcomes and long-term developmental problems. Despite this, a significant number of women drink during pregnancy. Although most prenatal care providers are asking women about alcohol use, validated screening tools are infrequently employed. Research has demonstrated that currently available screening methods and intervention techniques are effective in identifying and reducing pregnancy drinking. Implementing universal screening and appropriate intervention for pregnancy alcohol use should be a priority for prenatal care providers, as these efforts could substantially improve pregnancy, birth, and longer term developmental outcomes for those affected.

Background: COVID-19 is an ongoing pandemic. As of 11 May 2020, there are 4 013 728confirmed cases and 278 993 deaths. Smoking has been named as one possible factor regardingillness progression and severity. Aim: The aim of this systematic literature review is to examine if smokers are more at riskconsidering disease severity. Methods: This is a systematic literature study using the PubMed database. Inclusion andexclusion criteria were specified by using the PICOS format. Free text words and MeSH wordswere combined to create a search plan. The search was conducted twice, 26 April 2020 and 12May 2020. Full text articles were examined for eligibility by using inclusion and exclusioncriteria. An estimation of bias was conducted by using the MINORS criteria. Result: A total of seven articles were included. Of those, 5 reported a statistically significantrelationship between smoking and disease progression or death. Of these, 4 articles foundstatistical significance when correcting for confounders (hypertension, COPD, ischemic heartdisease, cardiac insufficiency). Conclusions: The result of this systematic literature review suggests that smoking enhancesthe severity of COVID-19. Due to the limited number of patients combined with a narrowgeographic area being studied, more research is needed to further evaluate and establish therelationship between smoking and COVID-19.

This study investigates the suitability of beta-2-microglobulin (β2-microglobulin), lactate and angiotensin-converting enzyme (ACE) as biomarkers, given the good availability of these parameters in routine diagnostics but lack of data in this regard. For this purpose, 6,310 CSF samples obtained at the Neurological Clinic of the University Hospital of Würzburg were analyzed. Closer analysis was carried out of 276 cases with non-inflammatory neurological diseases (NIND; control group) and 438 MS cases not taking an immunotherapy treatment (study group). In the MS cases, the form of progression of the disease and the disease activity (clinical relapses, progression index) were recorded. A clear correlation could be seen between age and CSF levels of β2-microglobulin, lactate and ACE in both the MS and control groups, whereby a correction was required for the subsequent comparison studies; this could also at least partly explain the contradictory data obtained in other studies to date. The MS cases showed elevated β2-microglobulin and lactate levels and decreased ACE levels in CSF compared to the controls. In both groups, there was a positive correlation between β2-microglobulin and ACE levels. In the separate analysis of the forms of progression of MS, cases with clinically-isolated syndrome (CIS) and relapsing-remitting MS (RRMS) revealed elevated β2-microglobulin levels, whilst cases with secondary-progressive or primary-progressive MS (SPMS or PPMS) did not. Lactate levels were only increased in cases of CIS. Cases with a relapsing course showed reduced ACE levels. The disease activity could not reliably be mapped by the parameters. Lactate levels tended to be elevated during a relapse, but this result was no longer significant after correction. Lactate levels also showed a positive correlation with the progression index. Our findings in this study provide evidence that the examined analysis parameters cannot be used in isolation to assess progression, disease activity and duration of disease. However, the significant differences between relapsing and chronic-progressive courses support the hypothesis of different underlying mechanisms of pathogenesis, and could serve as a starting basis for further studies. / In der vorliegenden Arbeit wurde die Eignung der im Rahmen der Routinediagnostik verfügbaren, aber unzu¬reichend charakterisierten Analyten Beta-2-Mikroglobulin (β2-Mikroglobulin), Laktat und Angiotensin-Converting Enzyme (ACE) als Biomarker untersucht. Dazu wurden 6.310 an der Neurologischen Klinik des Universitätsklinikums Würzburg gewonnene Liquorproben analysiert. Näher analysiert wurden 276 Fälle mit nicht entzünd¬lichen neurologischen Erkrankungen (NIND; Kontrollgruppe) und 438 nicht immuntherapeutisch behandelte MS-Fälle (Untersuchugsgruppe). Bei den MS-Fällen wurde die Verlaufs¬form und Krankheitsaktivität (klinische Schübe, Progressionsindex) dokumentiert. Es zeigte sich eine deutliche Altersabhängigkeit der Liquorspiegel von β2-Mikroglobulin, Laktat und ACE in der MS- und Kontrollgruppe, was für die sich anschließenden weiteren Vergleichsuntersuchungen eine Korrektur erforderte und zumindest teilweise die wider¬sprüchliche Datenlage bisheriger Studien erklären könnte. MS-Fälle zeigten im Liquor im Vergleich zu Kontrollen erhöhte β2-Mikroglobulin- und Laktat- sowie er¬niedrigte ACE-Spiegel. In beiden Gruppen korrelierten die β2-Mikroglobulin- und ACE-Spiegel positiv miteinander. Bei der getrennten Analyse der MS-Verlaufsformen zeigten Fälle mit klinisch isoliertem Syndrom (CIS) und schubförmig remittierender MS (RRMS) erhöhte β2-Mikroglobulin-Spiegel, Fälle mit sekundär bzw. primär pro¬gredienter MS (SPMS bzw. PPMS) dagegen nicht. Die Laktat-Spiegel waren lediglich bei CIS-Fällen erhöht. Fälle mit schubförmigen Verläufen zeigten reduzierte ACE-Spiegel. Die Krankheitsaktivität wurde durch die Parameter nicht zuverlässig abgebildet. Die Laktat-Spiegel waren tendenziell bei einem Schub erhöht, das Ergebnis war nach Korrektur aber nicht mehr signifikant. Die Laktat-Spiegel korrelierten zudem positiv mit dem Progressionsindex. Die vorliegenden Befunde belegen, dass die untersuchten Analyten alleine nicht in der Lage sind, die Verlaufsform, Krankheitsaktivität und -dauer zu beurteilen. Die deutlichen Unterschiede zwischen schubförmigen und chronisch progredienten Verläufen unterstützen jedoch die Hypothese unterschiedlicher zugrundeliegender Pathomechanismen und könnten als Ausgangspunkt für weitere Untersuchungen dienen.

Experiences of trauma and maltreatment are frequent predictors of poor physical and mental health outcomes in adulthood. Existing literature also suggests an impact of developmental adversity on criminality and aggressive behavior, though little research exists describing the effects of cumulative adversity in forensic mental health samples. In the current study of 381 forensic mental health inpatients, rates of trauma, neglect, and parental substance abuse are reported in comparison with community norms. Cumulative adversity and the occurrence of foster care placement are examined via linear and logistic regression analyses in relation to age at first arrest, first psychiatric hospitalization, and onset of aggression, as well as history of suicide attempts and non-suicidal self-injury. Results revealed that experiences of developmental adversity were more common among participants than have been reported in community samples using the ACE survey, and that there were differential effects of gender on the prevalence of traumas experienced. Cumulative adversity scores were significantly associated with all outcomes, though the addition of foster care placement to the model significantly contributed to understanding outcomes, and in some cases, removed the effect of cumulative adversity. Implications and direction for future study are discussed.

No description available.

Exposure to abuse, neglect, and familial dysfunction in childhood is connected to long-term negative effects on mental and physical health in adulthood. Current research of adverse childhood experience is overwhelmingly focused on community samples. Those populations that tend to experience a greater number of adversities (e.g., high-risk forensic populations) are largely overlooked. Studies investigating differential risk factors and outcomes among those in high-risk populations could indicate environmental 2015 Appalachian Student Research Forum Page 107 responsiveness to experiences of abuse, neglect, and household dysfunction in early development. A pilot study was conducted to investigate the prevalence and severity of childhood trauma, maltreatment, and familial dysfunction using the Adverse Childhood Experience (ACE) survey in a sample of forensic mental health offenders. Participants were randomly selected forensic inpatients (n = 185) from a maximum- and intermediate-security psychiatric facility. The sample is predominantly male (81.0%) and majority Caucasian (56.0%), African American (40.0%), and Hispanic (2.0%) with a mean age of 42.5 (SD=13.2). Approximately 29.0% of the current forensic sample has experienced 4 or more adversities in childhood (e.g., intrafamilial sexual abuse). This is a significantly higher percentage compared to the Center for Disease Control community norms of 12.5% indicating that a greater number of childhood adversities were experienced by the current sample of forensic mental health inpatients than in the general population. Additionally, significant percentages of diagnosed mental health disorders have been revealed. Diagnosed mental disorders in the current sample include, but are not limited to: psychotic disorders (59.0%), intellectual disability or cognitive developmental disorders (57.3%), mood disorders (45.0%), impulse disorders (22.2%), and post-traumatic stress disorder (13.0%). Comprehension of type, severity, and length of exposure to adversities, environmental responsiveness to abuse, maltreatment and familial dysfunction, and the onset and severity of mental and behavioral health outcomes are needed to better inform treatment, intervention, and rehabilitation of forensic psychiatric inpatient populations.