No Muslims Allowed? An analysis of the State of Pluralism in the West

Dissertação de Mestrado apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Relações Internacionais com o Mundo Árabe e Islâmico.

Os recetores da melatonina como novos alvos de fármacos antidepressivos

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Occupational lead neurotoxicity: A behavioural and electrophysiological evaluation. study design and year one results.

To evaluate the effects of chronic lead exposure on the nervous system in adults, a set of neurobehavioural and electrophysiological tests was administered to 99 lead exposed foundry employees and 61 unexposed workers. Current and past blood lead concentrations were used to estimate the degree of lead absorption; all previous blood lead concentrations had been less than or equal to 90 micrograms/100 ml. Characteristic signs (such as wrist extensor weakness) or symptoms (such as colic) of lead poisoning were not seen. Sensory conduction in the sural nerve was not affected. By contrast, various neurobehavioural functions deteriorated with increasing lead burden. Workers with blood lead concentrations between 40 and 60 micrograms/100 ml showed impaired performance on tests of verbal concept formation, visual/motor performance, memory, and mood. Thus impairment in central nervous system function in lead exposed adults occurred in the absence of peripheral nervous system derangement and increased in severity with increasing lead dose.

Occupational lead neurotoxicity: Improvement in behavioural effects after reduction of exposure.

To evaluate critical exposure levels and the reversibility of lead neurotoxicity a group of lead exposed foundry workers and an unexposed reference population were followed up for three years. During this period, tests designed to monitor neurobehavioural function and lead dose were administered. Evaluations of 160 workers during the first year showed dose dependent decrements in mood, visual/motor performance, memory, and verbal concept formation. Subsequently, an improvement in the hygienic conditions at the plant resulted in striking reductions in blood lead concentrations over the following two years. Attendant improvement in indices of tension (20% reduction), anger (18%), depression (26%), fatigue (27%), and confusion (13%) was observed. Performance on neurobehavioural testing generally correlated best with integrated dose estimates derived from blood lead concentrations measured periodically over the study period; zinc protoporphyrin levels were less well correlated with function. This investigation confirms the importance of compliance with workplace standards designed to lower exposures to ensure that individual blood lead concentrations remain below 50 micrograms/dl.

P-glycoprotein inhibition as a strategy to increase drug delivery across the blood-brain barrier: focus on antidepressants

Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.

Immune and stress factors in the pathophysiology of the mdx mouse model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a fatal multi-system neuromuscular disease caused by loss of dystrophin. The loss of dystrophin from membranes of contractile muscle cells and the dysregulation of the DAPC, induces chronic inflammation due to tissue necrosis and eventual replacement with collagen which weakens muscular force and strength. Dystrophin deficiency may cause under-diagnosed features of DMD include mood disorders such as depression and anxiety and dysfunction of the gastrointestinal tract. The first study in the thesis examined mood in the dystrophin-deficient mdx mouse model of DMD and examined the effects of the tri-cyclic antidepressant, amitriptyline on behaviours. Amitriptyline had anti-depressant and anxiolytic effects in the mdx mice possibly through effects on stress factors such as corticotrophin-releasing factor (CRF). This antidepressant also reduced skeletal muscle inflammation and caused a reduction in circulating interleukin (IL)-6 levels. In the second and third studies, we specifically blocked IL-6 signalling and used Urocortin 2, CRFR2 agonist to investigate their potential as therapeutic targets in mdx mice pathophysiology. Isometric and isotonic contractile properties of the diaphragm, were compared in mdx mice treated with anti IL-6 receptor antibodies (anti IL-6R) and/or Urocortin 2. Deficits in force production, work and power detected in mdx mice were improved with treatment. In study three I investigated contractile properties in gastrointestinal smooth muscle. As compared to wild type mice, mdx mice had slower faecal transit times, shorter colons with thickened muscle layers and increased contractile activity in response to recombinant IL-6. Blocking IL-6 signalling resulted in an increase in colon length, normalised faecal output times and a reduction in IL-6-evoked contractile activity. The findings from these studies indicate that for both diaphragm and gastrointestinal function in a dystrophin-deficient model, targeting of IL-6 and CRFR2 signalling has beneficial therapeutic effects.

Identifying novel molecular mechanisms of ghrelin receptor signalling underlying neural control of food intake: interaction with stress and impulsivity

The gut-hormone, ghrelin, activates the centrally expressed growth hormone secretagogue 1a (GHS-R1a) receptor, or ghrelin receptor. The ghrelin receptor is a G-protein coupled receptor (GPCR) expressed in several brain regions, including the arcuate nucleus (Arc), lateral hypothalamus (LH), ventral tegmental area (VTA), nucleus accumbens (NAcc) and amygdala. Activation of the GHS-R1a mediates a multitude of biological activities, including release of growth hormone and food intake. The ghrelin signalling system also plays a key role in the hedonic aspects of food intake and activates the dopaminergic mesolimbic circuit involved in reward signalling. Recently, ghrelin has been shown to be involved in mediating a stress response and to mediate stress-induced food reward behaviour via its interaction with the HPA-axis at the level of the anterior pituitary. Here, we focus on the role of the GHS-R1a receptor in reward behaviour, including the motivation to eat, its anxiogenic effects, and its role in impulsive behaviour. We investigate the functional selectivity and pharmacology of GHS-R1a receptor ligands as well as crosstalk of the GHS-R1a receptor with the serotonin 2C (5-HT2C) receptor, which represent another major target in the regulation of eating behaviour, stress-sensitivity and impulse control disorders. We demonstrate, to our knowledge for the first time, the direct impact of GHS-R1a signalling on impulsive responding in a 2-choice serial reaction time task (2CSRTT) and show a role for the 5-HT2C receptor in modulating amphetamine-associated impulsive action. Finally, we investigate differential gene expression patterns in the mesocorticolimbic pathway, specifically in the NAcc and PFC, between innate low- and high-impulsive rats. Together, these findings are poised to have important implications in the development of novel treatment strategies to combat eating disorders, including obesity and binge eating disorders as well as impulse control disorders, including, substance abuse and addiction, attention deficit hyperactivity disorder (ADHD) and mood disorders.

Summer Sprite for Orchestra

Summer Sprite for Orchestra was completed in December, 2004. The piece originated from a singular encounter with little angels at Chang-Kyung Palace, which is the oldest and the most beautiful palace in Korea, and where the kings of the Chosun Dynasty (1393-1897) lived. This encounter was in the summer of 2002. I certainly could not prove that those angels I met were real. Possibly they were the reflection of drops of water after a sudden shower on that summer day. However, I definitely remember that short, unforgettable, and mysterious moment and the angels' beautiful dance-like celebration. Summer Sprite is based on these special memories and the encounter with the little angels that summer. Summer Sprite consists of 3 movements: "Greeting," "Encounter," and "Celebration." These follow the course of my encounter with the little angels. In Summer Sprite, I wished to describe the image of the angels as well as the progression of greeting, encounter, and celebration with them. The moods that follow in Summer Sprite are by turns lyrical, poetic, fantastic, mysterious, and dream-like. In each movement, I describe the meeting of angels and composer through the use of the soloists -- violin (sometimes viola) and cello. As suggested by the subtitle of the first movement, "Greeting" portrays the moment when a surprised I met the angels. It begins with tam-tam, marimba, harp, and piano and sets a mysterious and dark mood. The second movement, "Encounter," is shorter than the first movement. This movement provides a more tranquil mood as well as more unique timbres resulting from the use of mutes and special instruments (English horn, harp, crotales, suspended cymbal, and celesta). The delicate expression of the percussion is particularly important in establishing the static mood of this movement . The last movement, °?Celebration,°± is bright and energetic. It is also the longest. Here, I require the most delicate changes of dynamics and tempo, the most vigorous harmonies, and the fastest rhythmic figures, as well as the most independent, lyrical, and poetic melodies. For bright orchestral tone color, I used various kinds of percussion such as timpani, xylophone, marimba, vibraphone, cymbals, side drum, tambourine, triangle, and bass drum. This last movement is divided rondo-like into five sections: The first (mm.1-3), second (mm.4 - rehearsal number 1), third (rehearsal numbers 2-4), fourth (rehearsal numbers 5-7), and fifth, (rehearsal numbers 8 -18). To sum up, Summer Sprite describes an unforgettable and mysterious moment in a my life. My intention was to portray this through a concerto-like framework. A model for this would be Brahms°Ø °?Double Concerto°± in A minor, op.102, in which the solo cello stands for my angel and the solo violin (sometimes solo viola) for me.

Autonomic cardiovascular dysregulation as a potential mechanism underlying depression and coronary artery bypass grafting surgery outcomes.

BACKGROUND: Coronary artery bypass grafting (CABG) is often used to treat patients with significant coronary heart disease (CHD). To date, multiple longitudinal and cross-sectional studies have examined the association between depression and CABG outcomes. Although this relationship is well established, the mechanism underlying this relationship remains unclear. The purpose of this study was twofold. First, we compared three markers of autonomic nervous system (ANS) function in four groups of patients: 1) Patients with coronary heart disease and depression (CHD/Dep), 2) Patients without CHD but with depression (NonCHD/Dep), 3) Patients with CHD but without depression (CHD/NonDep), and 4) Patients without CHD and depression (NonCHD/NonDep). Second, we investigated the impact of depression and autonomic nervous system activity on CABG outcomes. METHODS: Patients were screened to determine whether they met some of the study's inclusion or exclusion criteria. ANS function (i.e., heart rate, heart rate variability, and plasma norepinephrine levels) were measured. Chi-square and one-way analysis of variance were performed to evaluate group differences across demographic, medical variables, and indicators of ANS function. Logistic regression and multiple regression analyses were used to assess impact of depression and autonomic nervous system activity on CABG outcomes. RESULTS: The results of the study provide some support to suggest that depressed patients with CHD have greater ANS dysregulation compared to those with only CHD or depression. Furthermore, independent predictors of in-hospital length of stay and non-routine discharge included having a diagnosis of depression and CHD, elevated heart rate, and low heart rate variability. CONCLUSIONS: The current study presents evidence to support the hypothesis that ANS dysregulation might be one of the underlying mechanisms that links depression to cardiovascular CABG surgery outcomes. Thus, future studies should focus on developing and testing interventions that targets modifying ANS dysregulation, which may lead to improved patient outcomes.

Hippocampus shape analysis and late-life depression.

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F(1,103) = 5.26; p = 0.0240) but not right hippocampus volume (F(1,103) = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms.

The enduring impact of transient emotions on decision making

People often do not realize they are being influenced by an incidental emotional state. As a result, decisions based on a fleeting incidental emotion can become the basis for future decisions and hence outlive the original cause for the behavior (i.e., the emotion itself). Using a sequence of ultimatum and dictator games, we provide empirical evidence for the enduring impact of transient emotions on economic decision making. Behavioral consistency and false consensus are presented as potential underlying processes. © 2009 Elsevier Inc. All rights reserved.

The Scherzo in Selected Works for Piano

This performance project will cover performing issues in terms of technique in the scherzo. The Dictionary of Musical Terms defines technique as "the system of creating music, the musical slull to show personality by controlling tones that is not an abstract theory but a practical ability in composition or performance." My project focuses on techniques in fast tempos, specifically those found in the scherzo form and in concertos containing a scherzo character. The term scherzo has varied in its meaning and form throughout history. In the Baroque period, a scherzo was a work of light vocal or instrumental character. In the Classical period, scherzo still meant light in style, but it also indicated a quick tempo, often in 2/4 time. The scherzo was usually a single movement in a suite or multi-movement work. Like the minuet form, the scherzo contained a contrasting trio section. The scherzo was also standard in Romantic and post-Romantic symphonies and related genres. Because of the high degree of subjectivity in Romantic music, genres that stressed emotional content over abstract form developed rapidly. Some composers even wrote one-movement pieces entitled scherzo. These pieces became very important because they usually expressed a particular character or mood. The objective of my dissertation project is to research scherzo-like concertos, scherzo as single movements in larger forms, and scherzo as independent works. My first recital will consist of two concertos with a scherzo-like character. These are Mozart's Piano Concerto No. 9 i ?nl Major; K. 271 and Ravel's Piano Concerto in G Major. I will perform these works in December 2002 with a second piano. In addition, I will perform the Ravel with an orchestra in 2003. My second recital will consist of two parts. The fxst half presents multi-movement works with scherzo movements. The pieces are Haydn's Piano Sonata No. 3 in F Majol; Hob. WI/9, Beethoven's Piano Sonata No. 10 in G Major; Op. 14, No. 2. The second half presents independent four scherzi by Chopin. The final program will also include multi-movement works containing scherzo and independent scherzo. These are Prokofiev's Piano Sonata No. 2 in D minor, Op. 14, Grieg Lyric Pieces Op. 54, Schubert Zwei Scherzi D. 593 and Copland Scherzo humoristique; Le Chat et la Souris (The Cat and the Mouse).

Selected Works from Character Pieces in the 19th - Early 20th Centuries

During the Romantic Era, the character piece flourished and became one of the most important genres. Even though character pieces existed as early as the eighteenth century, it was not until the nineteenth century that Romantic Era literary figures discovered that music was as powerful as any other artistic medium in expressing unspeakable emotions. The character piece allowed composers to express a definite mood, a programmatic idea, or a pictorial association. Character pieces often have titles that suggest briehess or casualness, such as a Beethoven Bagatelle, a Schubert Impromptu or Moment musicaux. Others have expressive programmatic titles, such as Schumann's Kreisleriana and Liszt's Apres une lecture de Dante. Ths dissertation was based on selected works from the nineteenth century and early-twentieth century in order to demonstrate the great variety of musical thought and stylistic development. I have examined composers from different countries and of different nationalities to establish what and how they contributed to the remarkable diversity in this genre. The selected works allowed for very personal programs. These concerts, in addition to being good combinations of pieces, are representative of the genre. The first program consisted of Chopin's Preludes, Op. 28; three pieces from Debussy7s Images Books I and 11; and Liszt7s Apres une lecture de Dante. The second program included seven of Beethoven's Bagatelles, Op. 33; Schumann's Kinderscenen, Op. 15; Poulenc's Mouvements perpetuels and Intermezzo in A-jlat Major; Faure7s Nocturne in B Major, Op. 33, No. 2 and Impromptu No. 2 in F Minor; three of Mompou's Canciones y Danzas; four of Villa-Lobos Prole do bebe Suite No. 1; and Albkniz's Navarra. The third and final program comprised four selections from Rachrnaninoff s Moment musicaux, Op. 16; five pieces from Grieg's Lyric Pieces; and Arensky7s Suite No. 1 for Two Pianos and Suite No. 2 for Two Pianos. I wanted to bring out nuances specific to the individual composers and show how their character pieces helped in shaping the Romantic Era. Even in the twenty-first century, an era of highly specialized musical tastes, the popularity and accessibility of character pieces stand out.

Direct and Indirect Effects of Dissolved Organic Matter Source and Concentration on Denitrification in Northern Florida Rivers

Using a natural gradient of dissolved organic carbon (DOC) source and concentration in rivers of northern Florida, we investigated how terrestrially-derived DOC affects denitrification rates in river sediments. Specifically, we examined if the higher concentrations of DOC in blackwater rivers stimulate denitrification, or whether such terrestrially-derived DOC supports lower denitrification rates because (1) it is less labile than DOC from aquatic primary production; whether (2) terrestrial DOC directly inhibits denitrification via biochemical mechanisms; and/or whether (3) terrestrial DOC indirectly inhibits denitrification via reduced light availability to-and thus DOC exudation by-aquatic primary producers. We differentiated among these mechanisms using laboratory denitrification assays that subjected river sediments to factorial amendments of NO3- and dextrose, humic acid dosing, and cross-incubations of sediments and water from different river sources. DOC from terrestrial sources neither depressed nor stimulated denitrification rates, indicating low lability of this DOC but no direct inhibition; humic acid additions similarly did not affect denitrification rates. However, responses to addition of labile C increased with long-term average DOC concentration, which supports the hypothesis that terrestrial DOC indirectly inhibits denitrification via decreased autochthonous production. Observed and future changes in DOC concentration may therefore reduce the ability of inland waterways to remove reactive nitrogen. © 2013 Springer Science+Business Media New York.

Autobiographical memory for stressful events: the role of autobiographical memory in posttraumatic stress disorder.

To provide the three-way comparisons needed to test existing theories, we compared (1) most-stressful memories to other memories and (2) involuntary to voluntary memories (3) in 75 community dwelling adults with and 42 without a current diagnosis of posttraumatic stress disorder (PTSD). Each rated their three most-stressful, three most-positive, seven most-important and 15 word-cued autobiographical memories, and completed tests of personality and mood. Involuntary memories were then recorded and rated as they occurred for 2 weeks. Standard mechanisms of cognition and affect applied to extreme events accounted for the properties of stressful memories. Involuntary memories had greater emotional intensity than voluntary memories, but were not more frequently related to traumatic events. The emotional intensity, rehearsal, and centrality to the life story of both voluntary and involuntary memories, rather than incoherence of voluntary traumatic memories and enhanced availability of involuntary traumatic memories, were the properties of autobiographical memories associated with PTSD.