Antimicrobial effect of polymeric biomaterials for bone infection treatment

Dissertação de mestrado em Bioquímica, apresentada à Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2016.

A dyadic perspective on genito-pelvic pain : trauma antecedents and treatment effectiveness

La vestibulodynie provoquée (VP) est la forme la plus répandue de douleur génito-pelvienne/trouble de la pénétration et la cause la plus fréquente de douleur vaginale chez les femmes pré-ménopausées. Les femmes qui en souffrent rapportent plus de détresse psychologique ainsi qu’un fonctionnement sexuel appauvri, une diminution de la fréquence des activités sexuelles et du plaisir, et plus d’attitudes négatives à l’égard de la sexualité. Les recherches portant sur les couples souffrant de VP ont montré le rôle prépondérant des variables relationnelles dans la modulation des conséquences sexuelles et psychologiques pour les femmes et leurs partenaires. Cependant, aucune analyse dyadique n’a été appliquée au facteur de risque étiologique le plus robuste, soit la maltraitance durant l’enfance. Par ailleurs, malgré des recommandations répétées pour inclure le partenaire dans le traitement psychologique pour la VP, aucune étude à ce jour n’a examiné l’efficacité d’une psychothérapie qui inclut systématiquement le partenaire et dont la cible est le couple. L’objectif général de cette thèse a été d’utiliser une perspective dyadique afin d’examiner les antécédents de maltraitance et l’efficacité d’une intervention conçue pour améliorer les issues des couples souffrant de VP. Le premier article vise à examiner les liens entre la maltraitance durant l’enfance des femmes souffrant de VP et leurs partenaires, et leur fonctionnement sexuel, leur ajustement psychologique, leur satisfaction conjugale et enfin avec la douleur rapportée par les femmes durant les relations sexuelles. Quarante-neuf couples souffrant de VP ont complété des questionnaires auto-rapportés. La maltraitance durant l’enfance chez les femmes était associée à un fonctionnement sexuel plus faible chez les femmes et les hommes, une augmentation de l’anxiété chez les femmes seulement, et une douleur affective accrue durant les relations sexuelles. La maltraitance durant l’enfance chez les hommes était associée à un fonctionnement sexuel plus faible, moins de satisfaction conjugale, plus d’anxiété chez les femmes et les hommes, et une douleur affective accrue durant les relations sexuelles rapportée par les femmes. En se basant sur les recommandations issues des études empiriques, une thérapie cognitive et comportementale pour les couples (TCCC) souffrant de VP a été développée. Le deuxième article présente les résultats d’une étude pilote testant son efficacité, fidélité et faisabilité potentielles. Neuf couples ont complété des questionnaires auto-rapportés pré- et post-traitement. La TCCC de 12 rencontres était manualisée. Les femmes ont rapporté une amélioration significative de la douleur, du fonctionnement et de la satisfaction sexuels, et les partenaires ont rapporté une amélioration significative de leur satisfaction sexuelle. Les couples ont rapporté des niveaux élevés de satisfaction quant à la psychothérapie, et les psychothérapeutes ont rapporté suivre le manuel de traitement de manière fidèle. Le troisième article, s’appuyant sur les résultats prometteurs de l’étude pilote, décrit le protocole de recherche pour un essai clinique randomisé mesurant l’efficacité de la TCCC comparée à une intervention médicale de première ligne, la lidocaïne topique, pour le traitement de la VP. Enfin, les implications cliniques et théoriques de la thèse sont discutées.

The effect of anxiety and depression scores of couples who underwent assisted reproductive techniques on the pregnancy outcomes.

Objective: The aim of this study was to determine the effect of anxiety and depression scores of couples who underwent Assisted Reproductive Techniques (ART) on pregnancy outcomes. Method: This study was conducted as a prospective and comparative study with 217 couples. The study data was collected by using a semi-structured questionnaire and the Turkish version of the State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). The questionnaire, STAI and BDI were applied to couples who initiated ART treatment. Couples’ state anxiety scores were re-evaluated after embryo transfer (ET). Results: A significant relationship was found between the depression score of women and pregnancy outcome (p < 0.05). It was determined that anxiety scores for both men and women were higher before the ART procedure, but their anxiety scores decreased after ET (p < 0.05). Spouses of women with a negative pregnancy outcome had higher trait and state anxiety mean scores (p > 0.05) and lower depression scores (p <0.05) than spouses of women with a positive pregnancy outcome. Conclusion: Study results indicated that the anxiety and depression scores of couples who had achieved a positive pregnancy result were lower than for couples with a negative result. The results of this study will contribute to the health professionals especially to the nurses who spend the most time with couples in providing consulting services and supporting psychological status of couples during ART process in Turkey.

Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 μg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

Sodium hypochlorite effects on dentin bond strength and acid-base resistant zone formation by adhesive systems

Aim: To evaluate the effects of 10% NaOCl gel application on the dentin bond strengths and morphology of resin-dentin interfaces formed by three adhesives. Methods: Two etch-and-rinse adhesives (One-Step Plus, Bisco Inc. and Clearfil Photo Bond, Kuraray Noritake Dental) and one self-etch adhesive (Clearfil SE Bond, Kuraray Noritake Dental) were applied on dentin according to the manufacturers’ instructions or after the treatment with 10% NaOCl (ED-Gel, Kuraray Noritake Dental) for 60 s. For interfacial analysis, specimens were subjected to acid-base challenge and observed by SEM to identify the formation of the acid-base resistant zone (ABRZ). For microtensile bond strength, the same groups were investigated and the restored teeth were thermocycled (5,000 cycles) or not before testing. Bond strength data were subjected to two-way ANOVA and Tukey’s test (p<0.05). Results: NaOCl application affected the bond strengths for One-Step Plus and Clearfil Photo Bond. Thermocycling reduced the bond strengths for Clearfil Photo Bond and Clearfil SE Bond when used after NaOCl application and One-Step Plus when used as recommended by manufacturer. ABRZ was observed adjacent to the hybrid layer for self-etch primer. The etch-and-rinse systems showed external lesions after acid-base challenge and no ABRZ formation when applied according to manufacturer’s instructions. Conclusions: 10% NaOCl changed the morphology of the bonding interfaces and its use with etch-&-rinse adhesives reduced the dentin bond strength. Formation of ABRZ was material-dependent and the interface morphologies were different among the tested materials.

Deflazacort Versus Prednisolone: Randomized Controlled Trial in Treatment of Children With Idiopathic Nephrotic Syndrome

Background: Corticosteroids are the main therapy of nephrotic syndrome and goal of corticosteroid therapy is to obtain maximum clinical benefit with minimum adverse effects. Children are more vulnerable to side effects of corticosteroids related to growth and adrenal suppression, so a search for an alternative steroid with fewer side-effects is underway. Deflazacort is an oxazoline derivative and preliminary data suggest reduced osteoporosis, lesser growth retardation and weight gain with deflazacort. Objectives: This study was done to compare the effectiveness and safety of deflazacort in idiopathic nephrotic syndrome. Patients and Methods: Twenty five children with age between 2 to 12 years, with idiopathic nephrotic syndrome were enrolled. They were randomly assigned to receive deflazacort (Group A, n = 12) or prednisolone (Group B, n = 13) and were followed up for six months. Results: All children of group A and 11 of group B had remission. Two children from group B were steroid resistant. Mean time taken to induce remission was significantly (P = 0.012) less in group A (10.25 ± 2.41 days) than group B (12.55 ± 1.44 days). One patient in group A had relapse on follow up as compared to 3 in group B (P = 0.58). Statistically significant difference (P = 0.03) in change in mean height was found between group A (2.13 ± 0.50cm) and B (1.44 ± 0.45 cm), with group B gaining less height. Conclusions: Remission rate in both groups was comparable although time taken to induce remission was shorter in deflazacort group and there was a significant difference in change of mean height on follow up with prednisolone group gaining lesser height.

Effectiveness of Acceptance and Commitment Therapy for Depression, Psychological Well-Being and Feeling of Guilt in 7 - 15 Years Old Diabetic Children

Background: Diabetes imposes restrictions on physical, emotional, and social functioning of children and adolescents. Objectives: The aim of this study was to determine effectiveness of acceptance and commitment therapy (ACT) for depression, psychological well-being and feeling of guilt in 7 - 15 years old diabetic children. Patients and Methods: This was a clinical trial with pre-test and post-test design with control group. The study population consisted of 34 participants selected using convenient sampling out of all 7 - 15 years old patients that referred to the Diabetes Association of Tabriz. They were randomly allocated into two equal groups (experimental and control). The experimental group participated in therapy sessions and the control group did not receive any intervention. The research instruments were reynolds child depression scale (RCDS), eysenck feelings of guilt scale and satisfaction with life scale (SWLS). Results: Multivariate covariance analysis (MANCOVA) showed that the treatment was effective on variables of depression, psychological well-being and feeling guilty in 7 - 15 years old diabetic children (P < 0.001). Conclusions: The aforementioned treatment is effective and suggested to be used in other psychosomatic diseases of children.

Nivel de ansiedad y depresión en adolescentes varones con trastornos por consumo de sustancias psicoactivas en el centro de adicciones Hogar Crecer, 2011-2015

Antecedentes: la ansiedad y depresión son desórdenes mentales frecuentes en adolescentes con trastornos por consumo de sustancias, siendo crónicos y resistentes al tratamiento, asociándose a una morbilidad significativa. Objetivo general: determinar el nivel de ansiedad y depresión en adolescentes varones con trastornos por consumo de sustancias psicoactivas en el Centro de Adicciones Hogar Crecer. Materiales y métodos: estudio descriptivo, transversal, se recolectó información de 291 historias clínicas, desde el 01 de junio 2011 al 31 de diciembre 2015. La información se registró en un formulario pre-elaborado que incluye: datos sociodemográficos, patrón de consumo y resultados del test de Hamilton para ansiedad y depresión. Los datos se analizaron con el software SPSS 15.0, en las variables cuantitativas y cualitativas se obtuvo frecuencia y porcentaje. Resultados: de las 291 historias clínicas, 230 (79%) adolescentes tenían entre 15 a 19 años y 61 (21%) entre 10 a 14; según el patrón de consumo, 243 (83,5%) presentaron policonsumo. Presentaron ansiedad 263 (90,3%), de los cuales: 51,2% ansiedad leve, 27,8% ansiedad moderada y el 11,3% ansiedad grave, mientras que la depresión se presentó en 271 (93,1%), de los cuales: 32,6% depresión leve, 36,1% depresión moderada, 17,9% depresión grave y 6,5% depresión muy grave. Conclusiones: - La mayoría de los adolescentes eran estudiantes. - Los adolescentes presentaron principalmente policonsumo. - Se encontró una alta frecuencia de ansiedad y depresión. - El nivel de ansiedad que con mayor frecuencia se presentó fue ansiedad leve, mientras que para depresión, el nivel que mayormente se presentó fue depresión moderada

Short-term cognitive-behavioural group treatment for hoarding disorder: a naturalistic treatment outcome study

The study aim was to test whether a 12-week publically rebated group programme, based upon Steketee and Frost's Cognitive Behavioural Therapy-based hoarding treatment, would be efficacious in a community-based setting. Over a 3-year period, 77 participants with clinically significant hoarding were recruited into 12 group programmes. All completed treatment; however, as this was a community-based naturalistic study, only 41 completed the post-treatment assessment. Treatment included psychoeducation about hoarding, skills training for organization and decision making, direct in-session exposure to sorting and discarding, and cognitive and behavioural techniques to support out-of-session sorting and discarding, and nonacquiring. Self-report measures used to assess treatment effect were the Savings Inventory-Revised (SI-R), Savings Cognition Inventory, and the Depression, Anxiety and Stress Scales. Pre-post analyses indicated that after 12 weeks of treatment, hoarding symptoms as measured on the SI-R had reduced significantly, with large effect sizes reported in total and across all subscales. Moderate effect sizes were also reported for hoarding-related beliefs (emotional attachment and responsibility) and depressive symptoms. Of the 41 participants who completed post-treatment questionnaires, 14 (34%) were conservatively calculated to have clinically significant change, which is considerable given the brevity of the programme judged against the typical length of the disorder. The main limitation of the study was the moderate assessment completion rate, given its naturalistic setting. This study demonstrated that a 12-week group treatment for hoarding disorders was effective in reducing hoarding and depressive symptoms in an Australian clinical cohort and provides evidence for use of this treatment approach in a community setting. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: A 12-week group programme delivered in a community setting was effective for helping with hoarding symptoms with a large effect size. Hoarding beliefs (emotional attachment and responsibility) and depression were reduced, with moderate effect sizes. A third of all participants who completed post-treatment questionnaires experienced clinically significant change. Suggests that hoarding CBT treatment can be effectively translated into real-world settings and into a brief 12-session format, albeit the study had a moderate assessment completion rate.

PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate

BACKGROUND: Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer. OBJECTIVE: To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis. CONCLUSIONS: Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted. PATIENT SUMMARY: PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.

Effectiveness and efficiency in the treatment of gambling disorder : reflections on the Dodo Bird Conjecture

In the field of research into the treatment of problem gambling, researchers have been attempting to identify the treatment pathways that are effective in remediating gambling disorder among people seeking help. In spite of these efforts, research results remain equivocal in relation to which components of the various treatment options are effective, echoing the familiar claim that all psychotherapy treatments are effective, the Dodo Bird Conjecture.This recent tendency towards the revival of the Dodo Bird Conjecture in the field of gambling research is due to factors ranging from a continuing lack of clarity about the effective components of treatments, subjective therapist effects and the lack of validated repeated measures of outcome to assess changes in self-reported data on gambling urge: anxiety, depression and changes in the 'gambling disorder' diagnosis over time.

Adjunctive nutraceuticals for depression: a systematic review and meta-analyses

OBJECTIVE: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted. METHOD: A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. RESULTS: Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias). CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.

Depression screening and referral in cardiac wards: A 12-month patient trajectory

Background: Depression is common among patients with coronary heart disease (CHD) and has a major impact on their quality of life, morbidity and mortality. Aim: The aim of this study was to map the 12-month psychosocial outcomes of patients with CHD who were screened positive for depression in an acute cardiac ward.

Methods: A prospective cohort study was conducted of the psychosocial trajectory (depression, anxiety, wellbeing, social support, mental health service access) of 212 patients with CHD who were screened for depression after being admitted to acute cardiac wards of a major metropolitan hospital. Outcomes were assessed before hospital discharge and at one, three, six and 12 months post-discharge.

Results: Linear mixed models identified that those patients screened at ‘moderate to high’ risk of depression at baseline had higher levels of depression (F(1,173)=53.93, p<0.0001) and anxiety (F(1,180)=67.01, p<0.001), and lower levels of wellbeing (F(1,186)=42.47, p<0.001) and social support (F(1,177)=25.40, p<0.0001), compared to those at ‘no to low’ risk of depression. Levels of depression and wellbeing remained fairly constant over the 12-month trajectory. Surgical and medical treatment groups were of similar psychological composition over the 12-month period.

Conclusions: These findings attest to the effectiveness and predictive validity of a simple nurse-administered screening tool designed to identify depression in hospital patients with CHD and also indicate that a screening and referral tool alone is not sufficient to achieve optimal disease management. A collaborative care model involving family members and integrated pathways to primary care is recommended.

Caregiver burden as a predictor of depression among family and friends who provide care for persons with bipolar disorder

OBJECTIVES: Over one-third of caregivers of people with bipolar disorder report clinically significant levels of depressive symptoms. This study examined the causal relationship between depression and caregiver burden in a large sample of caregivers of adult patients with bipolar disorder. METHODS: Participants were 500 primary caregivers of persons with bipolar disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).This study evaluates the strength and direction of the associations between caregiver burden and depressive symptoms at baseline and at six- and 12-month follow-up using cross-lagged panel analyses, controlling for the clinical status of patients and sociodemographic variables. RESULTS: Higher levels of overall caregiver burden at baseline were associated with increased levels of depressive symptoms among caregivers at follow-up (F = 8.70, df = 1,290, p < 0.001), after controlling for baseline caregiver depression, gender, race, age, social support, and patients' clinical status. By contrast, caregiver depression at baseline was not significantly associated with caregiver burden at follow-up (F = 1.65, p = 0.20). CONCLUSIONS: Caregiver burden is a stronger predictor of caregiver depressive symptoms over time than the reverse. Interventions that help alleviate caregiver burden may decrease depressive symptoms.