Efeito do topiramato sobre o craving em usuários de crack

The study aims to analyze the effects of topiramato on the craving of crack users. It is an open crossover clinical trial involving users from the Psychosocial Care Center for Alcohol and Drugs (CAPSad) in city of Parnamirim, RN, approved by the CEP CAAE: 38710614.1.0000.5537, respecting the norms of the resolution n. 466/2012/CNS. The study produced preliminary two scientific papers: a theoretical essay and an integrative review, as a way of seeking the state of art. The first paper was based in the theoretical framework of Hinds, Chaves and Cypress, which focuses different contexts, from the issues of individual use to the coping policies in Brazil, highlighting that the situation and the complexity of the phenome requires coping strategies for the full attention to the user, family and society. As a result of the integrative review, among the 902 retrieved records, eight of them presented therapeutic schemes with positive effects for the craving of cocaine. They used nine different drugs. It is important to spot out that there was no result for the craving of crack. The data collection was conducted from December 2014 to July 2015 and has as sample predominantly single males. The sample was composed of 30 subjects who met the inclusion criteria: adults, age from 18 years, diagnosis of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for cocaine/crack; cognitive capacity preserved; attendance to the service, participated at least three visits in the 12 months prior to data collection; and accepted to be monitored in the proposed treatment. Data was analyzed using descriptive statistics from the Statistical Package of Support for Social Sciences (SPSS) on the instruments: 1) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), pointing out, among other results, that only 14% used crack/cocaine weekly during treatment, while 83% used daily or weekly after the washout period; 2) Barratt Impulsiveness Scale, with an average of 80.23 and 77.47 with and without drug treatment, respectively. An analysis from the Student t test show no significant differences in impulsivity with or without the drug; and 3) Cocaine-Craving Questionnaire-Brief (CCK-B), indicating that the number of users with craving intensity level is significantly higher without drug treatment (86%) than with treatment (33%). The analysis between craving and level of impulsivity showed that there is a low correlation (Pearson) between these two variables during treatment and after the washout, demonstrating that impulsivity has low influence on the outcome of drug therapy. As conclusion, it was noted that the topiramate produces positive effect on reducing the craving for crack users and their use is a relevant strategy for efficacy in the treatment of crack users.

Efeito do topiramato sobre o craving em usuários de crack

The study aims to analyze the effects of topiramato on the craving of crack users. It is an open crossover clinical trial involving users from the Psychosocial Care Center for Alcohol and Drugs (CAPSad) in city of Parnamirim, RN, approved by the CEP CAAE: 38710614.1.0000.5537, respecting the norms of the resolution n. 466/2012/CNS. The study produced preliminary two scientific papers: a theoretical essay and an integrative review, as a way of seeking the state of art. The first paper was based in the theoretical framework of Hinds, Chaves and Cypress, which focuses different contexts, from the issues of individual use to the coping policies in Brazil, highlighting that the situation and the complexity of the phenome requires coping strategies for the full attention to the user, family and society. As a result of the integrative review, among the 902 retrieved records, eight of them presented therapeutic schemes with positive effects for the craving of cocaine. They used nine different drugs. It is important to spot out that there was no result for the craving of crack. The data collection was conducted from December 2014 to July 2015 and has as sample predominantly single males. The sample was composed of 30 subjects who met the inclusion criteria: adults, age from 18 years, diagnosis of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for cocaine/crack; cognitive capacity preserved; attendance to the service, participated at least three visits in the 12 months prior to data collection; and accepted to be monitored in the proposed treatment. Data was analyzed using descriptive statistics from the Statistical Package of Support for Social Sciences (SPSS) on the instruments: 1) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), pointing out, among other results, that only 14% used crack/cocaine weekly during treatment, while 83% used daily or weekly after the washout period; 2) Barratt Impulsiveness Scale, with an average of 80.23 and 77.47 with and without drug treatment, respectively. An analysis from the Student t test show no significant differences in impulsivity with or without the drug; and 3) Cocaine-Craving Questionnaire-Brief (CCK-B), indicating that the number of users with craving intensity level is significantly higher without drug treatment (86%) than with treatment (33%). The analysis between craving and level of impulsivity showed that there is a low correlation (Pearson) between these two variables during treatment and after the washout, demonstrating that impulsivity has low influence on the outcome of drug therapy. As conclusion, it was noted that the topiramate produces positive effect on reducing the craving for crack users and their use is a relevant strategy for efficacy in the treatment of crack users.

Lung clearance index in adults and children with cystic fibrosis

Background: Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate endpoint in Cystic Fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometry. Further study of LCI as an endpoint in CF adults is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI over the complete age range of people with CF. Methods: Clinically stable adults and children with CF and age matched healthy controls were recruited. Results: LCI and spirometry data for 110 CF subjects and 61 controls were collected at a stable visit. CF Questionnaire-Revised (CFQ-R) was completed by 80/110 CF subjects. Fifty-six CF subjects completed a second stable visit. The LCI CV% was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (AUCROC=0.93 and 0.84) had greater combined sensitivity and specificity to discriminate between people with CF and controls compared to FEV1 (AUCROC=0.88 and 0.60) and FEF25-75 (AUCROC=0.87 and 0.68). LCI correlated significantly with the CFQ-R treatment burden in adults (r=-0.37; p<0.01) and children (r=-0.50; p<0.01). Washout tests were successful in 90% of CF subjects and were perceived as comfortable and easy to perform in both adults and children. Conclusions: These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as children.

Chemoprevention in BRCA1 Mutation Carriers—A Proof-of-Concept Study

Background: Women with germline BRCA1 mutations have a high lifetime risk of breast cancer, with the only available risk-reduction strategies being risk-reducing surgery or chemoprevention. These women predominantly develop triple-negative breast cancers; hence, it is unlikely that selective estrogen receptor modulators (serms) will reduce the risk of developing cancer, as these have not been shown to reduce the incidence of estrogen receptor–negative breast cancers. Preclinical data from our laboratory suggest that exposure to estrogen and its metabolites is capable of causing dna double-strand breaks (dsbs) and thus driving genomic instability, an early hallmark of BRCA1-related breast cancer. Therefore, an approach that lowers circulating estrogen levels and reduces estrogen metabolite exposure may prove a successful chemopreventive strategy.

Aims: To provide proof of concept of the hypothesis that the combination of luteinizing-hormone releasing-hormone agonists (lhrha) and aromatase inhibitors (ais) can suppress circulating levels of estrogen and its metabolites in BRCA1 mutation carriers, thus reducing estrogen metabolite levels in breast cells, reducing dna dsbs, and potentially reducing the incidence of breast cancer.

Methods: 12 Premenopausal BRCA1 mutation carriers will undergo baseline ultrasound-guided breast core biopsy and plasma and urine sampling. Half the women will be treated for 3 months with combination goserelin (lhrha) plus anastrazole (ai), and the remainder with tamoxifen (serm) before repeat tissue, plasma, and urine sampling. After a 1-month washout period, groups will cross over for a further 3 months treatment before final biologic sample collection. Tissue, plasma, and urine samples will be examined using a combination of immunohistochemistry, comet assays, and ultrahigh performance liquid chromatography tandem mass spectrometry to assess the impact of lhrha plus ai compared with serm on levels of dna damage, estrogens, and genotoxic estrogen metabolites. Quality of life will also be assessed during the study.

Results: This trial is currently ongoing.

Koffeinets ergogena effekter på power i överkropp

Koffein har sedan 1962 fram och tillbaka varit dopingklassat men är sedan 2004 ett tillåtet ergogent preparat inom idrotten. Flera studier har visat positiva resultat i uthållighetsidrotter och på maximal styrkeförmåga. Syftet med denna studie var att se om koffein har någon ergogen effekt på power i överkroppsmuskulaturen. I denna studie användes en dubbel-blindad, randomiserad cross-over design. En slumpmässig indelning inför det första testtillfället avgjorde ifall deltagarna började studien med koffein- eller placebosupplementering och bytte sedan supplementering inför testtillfälle två. Som supplementeringsmetod användes koffein i tuggummiform på grund av att det ger ett snabbare upptag. Power mättes genom testet sittande stöt med en kula på 5 kg. Resultatet visar på en mycket svag (ES=0,13) positiv förbättring av stötlängderna mellan interventionerna. En av anledningarna till det triviala resultatet tros kunna bero på att det urval som användes ej bestod av en homogengrupp vad gäller träningsbakgrund och prestationsnivå. På grund av detta är det svårt att dra några slutsatser om koffeinet har eller inte har några ergogena effekter på power i överkroppen.

Low- vs. high-glycemic load diets: effects on postprandial plasma free fatty acids

Thesis (Master's)--University of Washington, 2016-06

Diagnostic utility of thyroglobulin measurement in the fine needle aspirates from cervical lymph nodes: a case report

Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC). However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its routine association with cytology is recommended. We here describe the case of a 20 yr old girl complaining of the recent appearance of palpable non-painful laterocervical nodes in the neck. Ultrasound examination revealed the presence of 3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg protein and mRNA were determined in the needle washout. The cytological analysis was not diagnostic for the two CLNs, while that of the thyroid nodule reported the presence of colloid and groups of thyrocytes with normal morphology. Both CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA, suggestive of metastatic DTC. Based on these findings, the FNAC analysis was performed on the second smaller thyroid nodule suggesting (Tir4) the presence of PTC. The patient was then subjected to total thyroidectomy with lymph nodes resection of the central and homolateral compartments. The histological diagnosis confirmed the presence of a PTC in the small nodule and metastatic lymph nodes. In conclusion, this case confirms that the cytological diagnosis of cystic lymph nodes is challenging, and that the measurement of Tg protein and/or mRNA in the needle washout may overcome this limitation.

Asymptotic stability of a coupled Advection-Diffusion-Reaction system arising in bioreactor processes.

In this work, we perform an asymptotic analysis of a coupled system of two Advection-Diffusion-Reaction equations with Danckwerts boundary conditions, which models the interaction between a microbial population (e.g., bacterias), called biomass, and a diluted organic contaminant (e.g., nitrates), called substrate, in a continuous flow bioreactor. This system exhibits, under suitable conditions, two stable equilibrium states: one steady state in which the biomass becomes extinct and no reaction is produced, called washout, and another steady state, which corresponds to the partial elimination of the substrate. We use the method of linearization to give sufficient conditions for the asymptotic stability of the two stable equilibrium configurations. Finally, we compare our asymptotic analysis with the usual asymptotic analysis associated to the continuous bioreactor when it is modeled with ordinary differential equations.

Changes in Diadenosine Polyphosphates during Alignment-Fit and Orthokeratology Rigid Gas Permeable

Purpose.: To evaluate the levels of dinucleotides diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) in tears of patients wearing rigid gas permeable (RGP) contact lenses on a daily wear basis and of patients wearing reverse-geometry RGP lenses overnight for orthokeratology treatment. Methods.: Twenty-two young volunteers (10 females, 12 males; 23.47 ± 4.49 years) were fitted with an alignment-fit RGP lens (paflufocon B) for a month, and after a 15-day washout period they were fitted with reverse-geometry RGP lenses for corneal reshaping (paflufocon D) for another month. During each period, tears were collected at baseline day 1, 7, 15, and 28. Ap4A and Ap5A were measured by high-pressure liquid chromatography (HPLC). Additionally, corneal staining, break-up time (BUT), Schirmer test, and dryness symptoms were evaluated. Results.: Ap4A concentrations increased significantly from baseline during the whole period of daily wear of RGP lenses (P < 0.001); concentration was also significantly higher than in the orthokeratology group, which remained at baseline levels during the study period except at day 1 (P < 0.001) and day 28 (P = 0.041). While BUT and Schirmer remained unchanged in both groups, discomfort and dryness were significantly increased during alignment-fit RGP daily wear but not during the orthokeratology period. Conclusions.: Daily wear of RGP lenses increased the levels of Ap4A due to mechanical stimulation by blinking of the corneal epithelium, and this is associated with discomfort. Also, orthokeratology did not produce symptoms or signs of ocular dryness, which could be a potential advantage over soft contact lenses in terms of contact lens-induced dryness.

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques. Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure. Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0-∞ , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %). Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.

Design and implementation of an optimal motion cueing algorithm for the Stuttgart Driving Simulator

Driving simulators emulate a real vehicle drive in a virtual environment. One of the most challenging problems in this field is to create a simulated drive as real as possible to deceive the driver's senses and cause the believing to be in a real vehicle. This thesis first provides an overview of the Stuttgart driving simulator with a description of the overall system, followed by a theoretical presentation of the commonly used motion cueing algorithms. The second and predominant part of the work presents the implementation of the classical and optimal washout algorithms in a Simulink environment. The project aims to create a new optimal washout algorithm and compare the obtained results with the results of the classical washout. The classical washout algorithm, already implemented in the Stuttgart driving simulator, is the most used in the motion control of the simulator. This classical algorithm is based on a sequence of filters in which each parameter has a clear physical meaning and a unique assignment to a single degree of freedom. However, the effects on human perception are not exploited, and each parameter must be tuned online by an engineer in the control room, depending on the driver's feeling. To overcome this problem and also consider the driver's sensations, the optimal washout motion cueing algorithm was implemented. This optimal control-base algorithm treats motion cueing as a tracking problem, forcing the accelerations perceived in the simulator to track the accelerations that would have been perceived in a real vehicle, by minimizing the perception error within the constraints of the motion platform. The last chapter presents a comparison between the two algorithms, based on the driver's feelings after the test drive. Firstly it was implemented an off-line test with a step signal as an input acceleration to verify the behaviour of the simulator. Secondly, the algorithms were executed in the simulator during a test drive on several tracks.