Hepatic capillariasis in rats: a new model for testing antifibrotic drugs

Rats infected with the helminth Capillaria hepatica regularly develop septal hepatic fibrosis that may progress to cirrhosis in a relatively short time. Because of such characteristics, this experimental model was selected for testing drugs exhibiting antifibrosis potential, such as pentoxifylline, gadolinium chloride and vitamin A. Hepatic fibrosis was qualitatively and quantitatively evaluated in liver samples obtained by partial hepatectomy and at autopsy. The material was submitted to histological, biochemical and morphometric methods. A statistically significant reduction of fibrosis was obtained with pentoxifylline when administered intraperitoneally rather than intravenously. Gadolinium chloride showed moderate activity when administered prophylactically (before fibrosis had started), but showed a poor effect when fibrosis was well advanced. No modification of fibrosis was seen after vitamin A administration. Hydroxyproline content was correlated with morphometric measurements. The model appears to be adequate, since few animals die of the infection, fibrosis develops regularly in all animals, and the effects of different antifibrotic drugs and administration protocols can be easily detected.

Reliability and validity of the interactive observation scale for psychiatric inpatients applied by nursing aides in daily ward practice

The main characteristic of the nursing Interactive Observation Scale for Psychiatric Inpatients (IOSPI) is the necessity of interaction between raters and patients during assessment. The aim of this study was to evaluate the reliability and validity of the scale in the "real" world of daily ward practice and to determine whether the IOSPI can increase the interaction time between raters and patients and influence the raters' opinion about mental illness. All inpatients of a general university hospital psychiatric ward were assessed daily over a period of two months by 9 nursing aides during the morning and afternoon shifts, with 273 pairs of daily observations. Once a week the patients were interviewed by a psychiatrist who filled in the Brief Psychiatric Rating Scale (BPRS). The IOSPI total score was found to show significant test-retest reliability (interclass correlation coefficient = 0.83) and significant correlation with the BPRS total score (r = 0.69), meeting the criteria of concurrent validity. The instrument can also discriminate between patients in need of further inpatient treatment from those about to be discharged (negative predictive value for discharge = 0.91). Using this scale, the interaction time between nursing aides and patients increased significantly (t = 2.93, P<0.05) and their opinion about the mental illness changed. The "social restrictiveness" factor of the opinion scale about mental illness showed a significant reduction (t = 4.27, P<0.01) and the "interpersonal etiology" factor tended to increase (t = 1.98, P = 0.08). The IOSPI was confirmed as a reliable and valid scale and as an efficient tool to stimulate the therapeutic attitudes of the nursing staff.

New [18F]Tracers for Alzheimer's Disease Imaging. Labeling Synthesis And Biological Testing

Alzheimer’s disease (AD) is the most common form of dementia. Characteristic changes in an AD brain are the formation of β-amyloid protein (Aβ) plaques and neurofibrillary tangles, though other alterations in the brain have also been connected to AD. No cure is available for AD and it is one of the leading causes of death among the elderly in developed countries. Liposomes are biocompatible and biodegradable spherical phospholipid bilayer vesicles that can enclose various compounds. Several functional groups can be attached on the surface of liposomes in order to achieve long-circulating target-specific liposomes. Liposomes can be utilized as drug carriers and vehicles for imaging agents. Positron emission tomography (PET) is a non-invasive imaging method to study biological processes in living organisms. In this study using nucleophilic 18F-labeling synthesis, various synthesis approaches and leaving groups for novel PET imaging tracers have been developed to target AD pathology in the brain. The tracers were the thioflavin derivative [18F]flutemetamol, curcumin derivative [18F]treg-curcumin, and functionalized [18F]nanoliposomes, which all target Aβ in the AD brain. These tracers were evaluated using transgenic AD mouse models. In addition, 18F-labeling synthesis was developed for a tracer targeting the S1P3 receptor. The chosen 18F-fluorination strategy had an effect on the radiochemical yield and specific activity of the tracers. [18F]Treg-curcumin and functionalized [18F]nanoliposomes had low uptake in AD mouse brain, whereas [18F]flutemetamol exhibited the appropriate properties for preclinical Aβ-imaging. All of these tracers can be utilized in studies of the pathology and treatment of AD and related diseases.

Reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS) for tardive dyskinesia in Brazilian patients

The objective of the present study was to evaluate the reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS). Videotaped interviews with 16 psychiatric inpatients treated with antipsychotic drugs for at least 5 years were evaluated. Reliability was assessed by the intraclass correlation coefficient (ICC) between three raters, two with and one without clinical training in psychopathology. Clinical utility was assessed by the difference between the scores of patients with (N = 11) and without (N = 5) tardive dyskinesia (TD). Patients with TD exhibited a higher severity of global evaluation by the AIMS (sum of scores: 4.2 ± 0.9 vs 0.4 ± 0.2; score on item 8: 2.3 ± 0.3 vs 0.4 ± 0.2, TD vs controls). The ICC for the global evaluation was fair between the two skilled raters (0.58-0.62) and poor between these raters and the rater without clinical experience (0.05-0.29). Thus, we concluded that the Portuguese version of the AIMS shows an acceptable inter-rater reliability, but only between clinically skilled raters, and that it is clinically useful.

Evaluating land-use related environmental impacts of biomass value chains for decision-support : Comparison and testing of methodologies proposed for environmental life cycle assessment

Life cycle assessment (LCA) is one of the most established quantitative tools for environmental impact assessment of products. To be able to provide support to environmentally-aware decision makers on environmental impacts of biomass value-chains, the scope of LCA methodology needs to be augmented to cover landuse related environmental impacts. This dissertation focuses on analysing and discussing potential impact assessment methods, conceptual models and environmental indicators that have been proposed to be implemented into the LCA framework for impacts of land use. The applicability of proposed indicators and impact assessment frameworks is tested from practitioners' perspective, especially focusing on forest biomass value chains. The impacts of land use on biodiversity, resource depletion, climate change and other ecosystem services is analysed and discussed and the interplay in between value choices in LCA modelling and the decision-making situations to be supported is critically discussed. It was found out that land use impact indicators are necessary in LCA in highlighting differences in impacts from distinct land use classes. However, many open questions remain on certainty of highlighting actual impacts of land use, especially regarding impacts of managed forest land use on biodiversity and ecosystem services such as water regulation and purification. The climate impact of energy use of boreal stemwood was found to be higher in the short term and lower in the long-term in comparison with fossil fuels that emit identical amount of CO2 in combustion, due to changes implied to forest C stocks. The climate impacts of energy use of boreal stemwood were found to be higher than the previous estimates suggest on forest residues and stumps. The product lifetime was found to have much higher influence on the climate impacts of woodbased value chains than the origin of stemwood either from thinnings or final fellings. Climate neutrality seems to be likely only in the case when almost all the carbon of harvested wood is stored in long-lived wooden products. In the current form, the land use impacts cannot be modelled with a high degree of certainty nor communicated with adequate level of clarity to decision makers. The academia needs to keep on improving the modelling framework, and more importantly, clearly communicate to decision-makers the limited certainty on whether land-use intensive activities can help in meeting the strict mitigation targets we are globally facing.

Design, implementation, and evaluation of an online water quality monitoring system in Lake Saimaa, Finland

Environmental threats are growing nowadays, they became global issues. People around the world try to face these issues by two means: solving the current affected environs and preventing non-affected environs. This thesis describes the design, implementation, and evaluation of online water quality monitoring system in Lake Saimaa, Finland. The water quality in Lake Saimaa needs to be monitored in order to provide responsible bodies with valuable information which allows them to act fast in order to prevent any negative impact on the lake's environment. The objectives were to design a suitable system, implement the system in Lake Saimaa, and then to evaluate the applicability and reliability of such systems for this environment. The needs for the system were first isolated, and then the design, needed modifications, and the construction of the system took place. After that was the testing of the system in Lake Saimaa in two locations nearby Mikkeli city. The last step was to evaluate the whole system. The main results were that the application of online water quality monitoring systems in Lake Saimaa can benefit of many advantages such as reducing the required manpower, time and running costs. However, the point of unreliability of the exact measured values of some parameters is still the drawback of such systems which can be developed by using more advanced equipments with more sophisticated features specifically for the purpose of monitoring in the predefined location.

Nanoparticle-Assisted Immunoassays for Point-of-Care Testing - With Specific Interest in Minimally Interference-Prone Assays for Cardiac Troponin I

Cardiac troponins (cTn) I and T are the current golden standard biochemical markers in the diagnosis and risk stratification of patients with suspected acute coronary syndrome. During the past few years, novel assays capable of detecting cTn‐concentrations in >50% of apparently healthy individuals have become readily available. With the emerging of these high sensitivity cTn assays, reductions in the assay specificity have caused elevations in the measured cTn levels that do not correlate with the clinical picture of the patient. The increased assay sensitivity may reveal that various analytical interference mechanisms exist. This doctoral thesis focused on developing nanoparticle‐assisted immunometric assays that could possibly be applied to an automated point‐of‐care system. The main objective was to develop minimally interference‐prone assays for cTnI by employing recombinant antibody fragments. Fast 5‐ and 15‐minute assays for cTnI and D‐dimer, a degradation product of fibrin, based on intrinsically fluorescent nanoparticles were introduced, thus highlighting the versatility of nanoparticles as universally applicable labels. The utilization of antibody fragments in different versions of the developed cTnI‐assay enabled decreases in the used antibody amounts without sacrificing assay sensitivity. In addition, the utilization of recombinant antibody fragments was shown to significantly decrease the measured cTnI concentrations in an apparently healthy population, as well as in samples containing known amounts of potentially interfering factors: triglycerides, bilirubin, rheumatoid factors, or human anti‐mouse antibodies. When determining the specificity of four commercially available antibodies for cTnI, two out of the four cross‐reacted with skeletal troponin I, but caused crossreactivity issues in patient samples only when paired together. In conclusion, the results of this thesis emphasize the importance of careful antibody selection when developing cTnI assays. The results with different recombinant antibody fragments suggest that the utilization of antibody fragments should strongly be encouraged in the immunoassay field, especially with analytes such as cTnI that require highly sensitive assay approaches.

The reliability of the Brazilian version of the Composite International Diagnostic Interview (CIDI 2.1)

The objective of the present study was to determine the reliability of the Brazilian version of the Composite International Diagnostic Interview 2.1 (CIDI 2.1) in clinical psychiatry. The CIDI 2.1 was translated into Portuguese using WHO guidelines and reliability was studied using the inter-rater reliability method. The study sample consisted of 186 subjects from psychiatric hospitals and clinics, primary care centers and community services. The interviewers consisted of a group of 13 lay and three non-lay interviewers submitted to the CIDI training. The average interview time was 2 h and 30 min. General reliability ranged from kappa 0.50 to 1. For lifetime diagnoses the reliability ranged from kappa 0.77 (Bipolar Affective Disorder) to 1 (Substance-Related Disorder, Alcohol-Related Disorder, Eating Disorders). Previous year reliability ranged from kappa 0.66 (Obsessive-Compulsive Disorder) to 1 (Dissociative Disorders, Maniac Disorders, Eating Disorders). The poorest reliability rate was found for Mild Depressive Episode (kappa = 0.50) during the previous year. Training proved to be a fundamental factor for maintaining good reliability. Technical knowledge of the questionnaire compensated for the lack of psychiatric knowledge of the lay personnel. Inter-rater reliability was good to excellent for persons in psychiatric practice.

Translation into Brazilian Portuguese, cultural adaptation and evaluation of the reliability of the Disabilities of the Arm, Shoulder and Hand Questionnaire

The objective of the present study was to translate, adapt and validate a Brazilian Portuguese version of the Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire. The study was carried out in two steps. The first was to translate the DASH into Portuguese and to perform cultural adaptation and the second involved the determination of the reliability and validity of the DASH for the Brazilian population. For this purpose, 65 rheumatoid arthritis patients of either sex (according to the classification criteria of the American College of Rheumatology), ranging in age from 18 to 60 years and presenting no other diseases involving the upper limbs, were interviewed. The patients were selected consecutively at the rheumatology outpatient clinic of UNIFESP. The following results were obtained: in the first step (translation and cultural adaptation), all patients answered the questions. In the second step, Spearman's correlation coefficients for interobserver evaluation ranged from 0.762 to 0.995, values considered to be highly reliable. In addition, intraclass correlation coefficients ranged from 0.97 to 0.99, also highly reliable values. Spearman's correlation coefficients and the intraclass correlation coefficients obtained during intra-observer evaluation ranged from 0.731 to 0.937 and from 0.90 to 0.96, respectively, being highly reliable values. The Ritchie Index showed a weak correlation with Brazilian DASH scores, while the visual analog scale of pain showed a good correlation with DASH score. We conclude that the Portuguese version of the DASH is a reliable instrument.

Reliability and validity of a Portuguese version of the Young Mania Rating Scale

The reliability and validity of a Portuguese version of the Young Mania Rating Scale were evaluated. The original scale was translated into and adapted to Portuguese by the authors. Definitions of clinical manifestations, a semi-structured anchored interview and more explicit rating criteria were added to the scale. Fifty-five adult subjects, aged 18 to 60 years, with a diagnosis of Current Manic Episode according to DSM-III-R criteria were assessed using the Young Mania Rating Scale as well as the Brief Psychiatric Rating Scale in two sessions held at intervals from 7 to 10 days. Good reliability ratings were obtained, with intra-class correlation coefficient of 0.97 for total scores, and levels of agreement above 0.80 (P < 0.001) for all individual items. Internal consistency analysis resulted in an alpha = 0.67 for the scale as a whole, and an alpha = 0.72 for each standardized item (P < 0.001). For the concurrent validity, a correlation of 0.78 was obtained by the Pearson coefficient between the total scores of the Young Mania Rating Scale and Brief Psychiatric Rating Scale. The results are similar to those reported for the English version, indicating that the Portuguese version of the scale constitutes a reliable and valid instrument for the assessment of manic patients.

The validity and 4-year test-retest reliability of the Brazilian version of the Eating Attitudes Test-26

In a cross-sectional study conducted four years ago to assess the validity of the Brazilian version of the Eating Attitudes Test-26 (EAT-26) for the identification of abnormal eating behaviors in a population of young females in Southern Brazil, 56 women presented abnormal eating behavior as indicated by the EAT-26 and the Edinburgh Bulimic Investigation Test. They were each matched for age and neighborhood to two normal controls (N = 112) and were re-assessed four years later with the two screening questionnaires plus the Composite International Diagnostic Interview (CIDI). The EAT results were then compared to diagnoses originating from the CIDI. To evaluate the temporal stability of the two screening questionnaires, a test-retest design was applied to estimate kappa coefficients for individual items. Given the prevalence of eating disorders of 6.2%, the CIDI psychiatry interview was applied to 161 women. Of these, 0.6% exhibited anorexia nervosa and 5.6%, bulimia nervosa (10 positive cases). The validity coefficients of the EAT were: 40% sensitivity, 84% specificity, and 14% positive predictive value. Cronbach's coefficient was 0.75. For each EAT item, the kappa index was not higher than 0.344 and the correlation coefficient was lower than 0.488. We conclude that the EAT-26 exhibited low validity coefficients for sensitivity and positive predictive value, and showed a poor temporal stability. It is reasonable to assume that these results were not influenced by the low prevalence of eating disorders in the community. Thus, the results cast doubts on the ability of the EAT-26 test to identify cases of abnormal eating behaviors in this population.

Exercise stress testing before and after successful multivessel percutaneous transluminal coronary angioplasty

Controversy exists regarding the diagnostic accuracy, optimal technique, and timing of exercise testing after percutaneous coronary intervention. The objectives of the present study were to analyze variables and the power of exercise testing to predict restenosis or a new lesion, 6 months after the procedure. Eight-four coronary multi-artery diseased patients with preserved ventricular function were studied (66 males, mean age of all patients: 59 ± 10 years). All underwent coronary angiography and exercise testing with the Bruce protocol, before and 6 months after percutaneous coronary intervention. The following parameters were measured: heart rate, blood pressure, rate-pressure product (heart rate x systolic blood pressure), presence of angina, maximal ST-segment depression, and exercise duration. On average, 2.33 lesions/patient were treated and restenosis or progression of disease occurred in 46 (55%) patients. Significant increases in systolic blood pressure (P = 0.022), rate-pressure product (P = 0.045) and exercise duration (P = 0.003) were detected after the procedure. Twenty-seven (32%) patients presented angina during the exercise test before the procedure and 16 (19%) after the procedure. The exercise test for the detection of restenosis or new lesion presented 61% sensitivity, 63% specificity, 62% accuracy, and 67 and 57% positive and negative predictive values, respectively. In patients without restenosis, the exercise duration after percutaneous coronary intervention was significantly longer (460 ± 154 vs 381 ± 145 s, P = 0.008). Only the exercise duration permitted us to identify patients with and without restenosis or a new lesion.

Evaluation of genotype resistance testing for salvage antiretroviral therapy at AIDS care centers from Ribeirão Preto, São Paulo, Brazil

The availability of HIV-1 genotype resistance testing (GRT) to clinicians has been insufficiently studied outside randomized clinical trials. The present study evaluated the outcome of salvage antiretroviral therapy (ART) recommended by an expert physician based on GRT in a non-clinical trial setting in Ribeirão Preto, Brazil. A prospective, open, nonrandomized study evaluating easy access to GRT at six Brazilian AIDS Clinics was carried out. This cooperative study analyzed the efficacy of treatment recommended to patients whose salvage ART was guided by GRT with that of treatment with ART based only on previous ART history. A total of 112 patients with ART failure were included in the study, and 77 of them were submitted to GRT. The median CD4 cell count and viral load for these 77 patients at baseline were (mean ± SD) 252.1 ± 157.4 cells/µL and 4.60 ± 0.5 log10 HIV RNA copies/mL, respectively. The access time, i.e., the time elapsed between ordering the GRT and receiving the result was, on average, 71.9 ± 37.3 days. The study results demonstrated that access to GRT followed by expert recommendations did not improve the time to persistent treatment failure when compared to conventional salvage ART. Access to GRT in this Brazilian community health care setting did not improve the long-term virologic outcomes of HIV-infected patients experiencing treatment failure. This result is probably related to the long time required to implement ART guided by GRT.

Noninvasive assessment of endothelial function and ST segment changes during exercise testing in coronary artery disease

Endothelial function (EF) plays an important role in the onset and clinical course of atherosclerosis, although its relationship with the presence and extent of coronary artery disease (CAD) has not been well defined. We evaluated EF and the ST segment response to an exercise test in patients with a broad spectrum of CAD defined by coronary angiography. Sixty-two patients submitted to diagnostic catheterization for the evaluation of chest pain or ischemia in a provocative test were divided into three groups according to the presence and severity of atherosclerotic lesions (AL): group 1: normal coronaries (N = 19); group 2: CAD with AL <70% (N = 17); group 3: CAD with AL ≥70% (N = 26). EF was evaluated by the percentage of flow-mediated dilatation (%FMD) in the brachial artery during reactive hyperemia induced by occlusion of the forearm with a pneumatic cuff for 5 min. Fifty-four patients were subjected to an exercise test. Gender and age were not significantly correlated with %FMD. EF was markedly reduced in both groups with CAD (76.5 and 73.1% vs 31.6% in group 1) and a higher frequency of ischemic alterations in the ST segment (70.8%) was observed in the group with obstructive CAD with AL ≥70% during the exercise test. Endothelial dysfunction was observed in patients with CAD, irrespective of the severity of injury. A significantly higher frequency of ischemic alterations in the ST segment was observed in the group with obstructive CAD. EF and exercise ECG differed among the three groups and may provide complementary information for the assessment of CAD.

Treadmill exercise testing of asymptomatic men and women without evidence of heart disease

The aim of this study was to test the hypothesis of differences in performance including differences in ST-T wave changes between healthy men and women submitted to an exercise stress test. Two hundred (45.4%) men and 241 (54.6%) women (mean age: 38.7 ± 11.0 years) were submitted to an exercise stress test. Physiologic and electrocardiographic variables were compared by the Student t-test and the chi-square test. To test the hypothesis of differences in ST-segment changes, data were ranked with functional models based on weighted least squares. To evaluate the influence of gender and age on the diagnosis of ST-segment abnormality, a logistic model was adjusted; P < 0.05 was considered to be significant. Rate-pressure product, duration of exercise and estimated functional capacity were higher in men (P < 0.05). Sixteen (6.7%) women and 9 (4.5%) men demonstrated ST-segment upslope ≥0.15 mV or downslope ≥0.10 mV; the difference was not statistically significant. Age increase of one year added 4% to the chance of upsloping of segment ST ≥0.15 mV or downsloping of segment ST ≥0.1 mV (P = 0.03; risk ratio = 1.040, 95% confidence interval (CI) = 1.002-1.080). Heart rate recovery was higher in women (P < 0.05). The chance of women showing an increase of systolic blood pressure ≤30 mmHg was 85% higher (P = 0.01; risk ratio = 1.85, 95%CI = 1.1-3.05). No significant difference in the frequency of ST-T wave changes was observed between men and women. Other differences may be related to different physical conditioning.