Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

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Os impactos psicossociais gerados pelo diagnóstico e tratamento da doença celíaca

Extraído da dissertação: "Os impactos psicossociais da Doença Celíaca" Programa de Pós Graduação em Ciências da Saúde, Universidade de Brasília, 2015.

A model of increased impulsivity in rats with bilateral parkinsonism treated with Pramipexole

Impulse control disorders (ICD) is a common side effect of the dopaminergic treatment in patients with Parkinson's disease, which is more associated with dopamine agonists than with levodopa. To understand its pathophysiology, reliable animal models are essential. Using the variable delay-to-signal (VDS) paradigm, impulsivity was evaluated in bilateral parkinsonian rats treated with pramipexole (PPX). In this test, rats have to introduce the snout into a nose poke that is signaled by a light (presented at variable delays) triggering the delivery of a food reward after a correct response. Reaching a stable baseline performance, a partial bilateral dopaminergic lesion with 6-OHDA was induced in the dorsolateral striatum (AP: +1mm, L: ±3.4mm, V:-4.7 mm, Bregma). Rats undertook the VDS test under 5 conditions: basal state, 6-OHDA-induced lesion, the effect of two doses of PPX (0,25mg/kg and 3mg/kg; Latin-square design), and the day after the last dose of PPX. Only the acute administration of 3 mg/kg of PPX significantly rised the number of premature responses, indicating an increase of impulsive behavior, in parkinsonian but not in sham rats. Both doses of PPX significantly decreased the accuracy of responding (correct/total number of responses) and increased the incorrect and perseverative (compulsive behavior) responses in both parkinsonian and sham treated groups when compared with saline-treated groups. In conclusion, PPX induced attention deficit (lack of accuracy) as well as compulsive behavior in control and parkinsonian rats, but increased impulsivity only in the parkinsonian animals. This model could constitute a valid tool to investigate the pathophysiology of ICD.

Feasibility of resting-state microstates neurofeedback

Despite major progress, currently available treatment options for patients suffering from schizophrenia remain suboptimal. Antipsychotic medication is one such option, and is helpful in acute phases of the disease. However, antipsychotics cause significant side-effects that often require additional medication, and can even trigger the discontinuation of treatment. Taken together, along with the fact that 20-30% of patients are medication-resistant, it is clear that new medical care options should be developed for patients with schizophrenia. Besides medication, an emerging option to treat psychiatric symptoms is through the use of neurofeedback. This technique has proven efficacy for other disorders and, more importantly, has also proven to be feasible in patients with schizophrenia. One of the major advantages of this approach is that it allows for the influence of brain states that otherwise would be inaccessible; i.e. the physiological markers underlying psychotic symptoms. EEG resting-state microstates are a very interesting electrophysiological marker of schizophrenia symptoms. Precisely, a specific class of resting-state microstates, namely microstate class D, has consistently been found to show a temporal shortening in patients with schizophrenia compared to controls, and this shortening is correlated with the presence positive psychotic symptoms. Under the scope of biological psychiatry, appropriate treatment of psychotic symptoms can be expected to modify the underlying physiological markers accompanying behavioral manifestations of a disease. We reason that if abnormal temporal parameters of resting-state microstates seem to be related to positive symptoms in schizophrenia, regulating this EEG feature might be helpful as a treatment for patients. The goal of this thesis was to prove the feasibility of microstate class D contribution self-regulation via neurofeedback. Given that no other study has attempted to regulate microstates via neurofeedback, we first tested its feasibility in a population of healthy subjects. In the first paper we describe the methodological characteristics of the neurofeedback protocol and its implementation. Neurofeedback performance was assessed by means of linear mixed effects modeling, which provided a complete profile of the neurofeedback’s training response within and between-subjects. The protocol included 20 training sessions, and each session contained three conditions: baseline (resting-state) and two active conditions: training (auditory feedback upon self-regulation performance) and transfer (self-regulation with no feedback). With linear modeling we obtained performance indices for each of them as follows: baseline carryover (baseline increments time-dependent) and learning and aptitude for each of the active conditions. Learning refers to the increase/decrease of the microstate class D contribution, time-dependent during each active condition, and aptitude refers to the constant difference of the microstate class D contribution between each active condition and baseline independent of time. The indices provided are discussed in terms of tailoring neurofeedback treatment to individual profiles so that it can be applied in future studies or clinical practice. In our sample of participants, neurofeedback proved feasible, as all participants at least showed positive results in one of the aforementioned learning indices. Furthermore, between-subjects we observed that the contribution of microstate class D across-sessions increased by 0.42% during baseline, 1.93% during training trials, and 1.83% during transfer. This range is expected to be effective in treating psychotic symptoms in patients. In the second paper presented in this thesis, we explored the possible predictors of neurofeedback success among psychological variables measured with questionnaires. An interesting finding was the negative correlation between “motivational incongruence” and some of the neurofeedback performance indices. Even though this finding requires replication, we discuss it in terms of the interfering effects of incompatible psychological processes with neurofeedback training requirements. In the third paper, we present a meta-analysis on all available studies that have related resting-state microstate abnormalities and schizophrenia. We obtained medium effect sizes for two microstate classes, namely C and D. Combining the meta-analysis results with the fact that microstate class D abnormalities are correlated with the presence of positive symptoms in patients with schizophrenia, these results add further support for the training of this precise microstate. Overall, the results obtained in this study encourage the implementation of this protocol in a population of patients with schizophrenia. However, future studies will have to show whether patients will be able to successfully self-regulate the contribution of microstate class D and, if so, whether this regulation will have an impact on symptomatology.

Estudo da viabilidade do processo de reciclagem do material descartado do sistema Zirkonzanh® de produção de próteses dentárias

At present, the material of choice for performing aesthetic dental prosthetic work is in the ceramic. Among them, the ceramic base of stabilized zirconia with 3% yttria (3Y - TZP) stand out for having excellent physical and mechanical properties. During the machining of blocks of zirconia in the laboratory to prepare the various types of prostheses, much of the material is given off in the form of powder, which is subsequently discarded. The waste of this material results in financial loss, reflecting higher final cost treatment for patients, as well as damage to the environment, thanks to the processes involved in the manufacture and disposal of the ceramic. This research, pioneered the recycling of zirconium oxide powder obtained during milling of dental crowns and bridges, we highlight the social and environmental aspects and aims to establish a protocol for the reuse of waste (powder of zirconia Zirkonzahn® system) discarded to obtain a new block of compacted zirconia to maintain the same mechanical and microstructural properties of commercial high-cost imported material. To compare with the commercial material, samples were uniaxially (20 MPa) and isostatically (100 MPa), and its mechanical and microstructural characterization was performed through tests of density, porosity, dilatometry, X-ray diffraction (XRD), hardness, fracture toughness, resistance to fracture electron microscopy (SEM) and analysis of grain size. The results observed in the samples were isostatically pressed similiares those obtained with samples from the commercial material demonstrating the viability of the process

The role of additive manufacturing in patient specific solutions

This dissertation investigates de role of the new additive manufacturing techniques in the treatment of pathologies with a patient-specific approach. Throughout this work the development methodology of these said products is explained in order to understand the different stages required to achieve a tailor made solution. The goal is to demonstrate the importance of the manufacturing technique and its capabilities to tailor-fit devices to patients and the adaptability of the process to tackle the most diverse situations. Three real cases are documented in order to prove the viability of the method and to showcase its advantages. Whenever possible patient-specific solutions are compared to their “off-the-shelf” counterparts in order to establish the pros and cons of each one of them. The dissertation is an insight into a possible future for the medical devices industry, where customization is expected to be the standard approach in the treatment of patients.

Gengivite Ulcerativa Necrosante (GUN)

Introdução: A Gengivite Ulcerativa Necrosante (GUN) é uma das patologias orais com mais décadas de estudo. A sua designação foi evoluindo ao longo dos anos até ter sido englobada na categoria das doenças periodontais necrosantes (DPN). As lesões provocadas pela GUN são consideradas únicas entre as doenças periodontais, principalmente pela sua apresentação clínica bastante distinta (Rowland, 1999). Apesar de ser uma doença com sinais muito próprios e fatores predisponentes bem estabelecidos, a etiologia e patogénese das lesões são muito mal compreendidas. O objetivo deste trabalho é efetuar uma revisão bibliográfica dos principais conceitos relativos a esta doença, defini-la e classificá-la, assim como fazer uma abordagem ao seu diagnóstico e respetivo plano de tratamento. Materiais e Métodos: Foi realizada uma pesquisa na base de dados da PubMed e da b-ON, utilizando como palavras-chave: “Necrotizing ulcerative gingivitis”, AND “Necrotizing periodontal disease”. Apenas foram pesquisados artigos em português e inglês, não tendo sido empregues quaisquer limites temporais, resultando num total de 32 artigos, complementado com uma obra literária. Resultados/Conclusões: Após análise da literatura é possível verificar que, mesmo os estudos mais recentes, revelam muitas dúvidas sobre esta doença, apesar das décadas de existência. Porém todos os estudos são unânimes em realçar um aspeto muito importante, a realização de um diagnóstico precoce é a chave para um tratamento adequado, criando, aos pacientes, as condições mínimas necessárias para uma adequada higiene oral e alimentação, que até aí a doença os obrigava a privar.

Left atrial appendage: anatomy and imaging landmarks pertinent to percutaneous transcatheter occlusion

Percutaneous left atrial appendage (LAA) closure represents a complementary option and effective treatment for patients at risk of thromboembolism, especially in patients for whom it may be difficult to achieve satisfactory anticoagulation control or where anticoagulation treatment is not possible or desirable. Effective and safe transcatheter LAA occlusion requires a detailed knowledge of crucial anatomic landmarks and endocardial morphologic variants of the LAA and its neighbouring structures.1 ,2 w1–w3 Our aim in this article is to provide the basic anatomic information that is important for the interventional cardiologist to know when planning an LAA occlusion procedure.

Hallazgos tomográficos como predictores del resultado funcional en edema macular secundario a oclusiones venosas retinianas

INTRODUCCIÓN: El Edema Macular (EM) es la principal causa de perdida de agudeza visual en pacientes con Oclusión Venosa Retiniana (OVR); luego del tratamiento, algunos pacientes persisten con mala agudeza visual. OBJETIVO: Realizar una Revisión Sistemática de la Literatura (RSL), para identificar la evidencia existente sobre factores tomográficos que predicen el resultado visual en pacientes con EM secundario a OVR. FUENTE DE LA INFORMACIÓN: PUBMED, MEDLINE, EMBASE, LILACS, COCHRANE, literatura gris. SELECCIÓN DE LOS ESTUDIOS: Ensayos Clínicos Controlados (ECC) y estudios observacionales analíticos. EXTRACCIÓN Y SÍNTESIS DE LOS DATOS: Dos investigadores seleccionaron los artículos de forma independiente. Se realizó una síntesis cualitativa de la información siguiendo las recomendaciones de la declaración PRISMA 2009. MEDIDAS Y DESENLACE PRINCIPAL: Grosor Retiniano Central (GRC), integridad de Banda Elipsoide e Integridad de Membrana Limitante Externa (MLE), determinados por SD OCT. El desenlace principal es la Agudeza Visual Mejor Corregida (AVMC) a los 6, 12,18 y/o 24 meses. RESULTADOS: Se identificaron 872 abstract y se incluyeron 8 artículos en el análisis cualitativo. Seis estudios evaluaron el GRC sin encontrar asociación con resultado visual final. Solo 2 estudios evaluaron y encontraron asociación estadísticamente significativa de la integridad de la MLE con el desenlace visual, Kang, H 2012 (r2 0,51 p 0,000), Rodriguez, F 2014 (p< 0,001). La integridad de la BE fue asociada a pronostico visual en 4 de 5 estudios que evaluaron esta variable, con resultados estadísticamente significativos. La AVMC de base también se asocio con desenlace visual en 4 de 5 estudios que la evaluaron. El mejor modelo que predice el resultado funcional según el estudio de Kang, H 2012 fue: Integridad de MLE, integridad de BE y AVMC de base (R2 0,671 p 0,000), a los 12 meses de seguimiento. CONCLUSION: La evidencia actual sugiere que la integridad de la BE y la MLE son predictores del resultados funcional en pacientes con EM secundario a OVR después de 6 o mas meses de seguimiento. Es necesario la realización de estudios controlados para llegar a resultados mas concluyentes.

Tratamiento quirúrgico del síndrome de apnea hipopnea obstructiva del sueño en la Clínica Rivas, Bogotá – Colombia

Introducción: El Síndrome de Apnea Hipopnea Obstructiva del Sueño es un trastorno respiratorio del sueño mayor ampliamente conocido, con importantes implicaciones para los pacientes y cuya incidencia ha venido en aumento durante los últimos años; comprende diversas manifestaciones clínicas que varían desde el ronquido hasta consecuencias cardiovasculares importantes. Objetivo: Describir la experiencia de los procedimientos quirúrgicos más utilizados para el tratamiento de pacientes con Trastornos Respiratorios del Sueño en la Clínica Rivas. Diseño: Estudio observacional descriptivo. Métodos: Revisión de 366 historias clínicas de pacientes con diagnóstico clínico y Polisomnográfico de SAHOS intervenidos quirúrgicamente debido al Trastorno Respiratorio del Sueño por rechazo de terapia de presión positiva en 3 años de observación. Resultados: Se evaluaron diferencias en medianas de los cambios del IAH, índice de Saturación de oxigeno basal y mínima, y el índice de microdespertares nocturnos tanto prequirúrgica como postquirúrgicamente. Como medida de evaluación secundaria se evaluaron las complicaciones quirúrgicas. Conclusión: En nuestra institución, como centro de referencia en apnea del sueño, la cirugía ha demostrado que disminuye de forma significativa gravedad del SAHOS y disminuye el riesgo de los pacientes con trastornos respiratorios del sueño que han rechazado el dispositivo de presión positiva.

Strategia terapeutica nei pazienti con ipertensione arteriosa polmonare a rischio intermedio

Le attuali linee guida stratificano il rischio dei pazienti con ipertensione arteriosa polmonare (IAP) in basso, intermedio e alto (rispettivamente con mortalità a 1 anno <5%, 5-10% e >10%). La maggior parte dei pazienti è però classificata nella categoria intermedia. Per stratificare ulteriormente questi pazienti, abbiamo valutato il ruolo prognostico dello stroke volume index (SVI) misurato al cateterismo cardiaco destro (CCDx) in 725 pazienti naïve da terapia con IAP idiopatica/ereditaria, associata a malattie del tessuto connettivo o cardiopatie congenite. I pazienti sono stati valutati al basale e 3-4 mesi dopo l'inizio della terapia (1° F-UP) con CCDx, livelli plasmatici di peptide natriuretico cerebrale (BNP), test dei 6 minuti (T6M) e classe funzionale OMS. Abbiamo applicato una tabella di rischio semplificata utilizzando i criteri: classe funzionale OMS, T6M, pressione atriale destra o livelli plasmatici di BNP e indice cardiaco (IC) o saturazione di ossigeno venoso misto (SvO2). Le classi di rischio sono state definite come: basso= almeno 3 criteri a basso rischio e nessun criterio ad alto rischio; alto= almeno 2 criteri ad alto rischio inclusi IC o SvO2; intermedio= tutti gli altri casi. Lo SVI, mediante la regressione di Cox, stratifica la prognosi dei pazienti a rischio intermedio al 1° F-UP [p=0.008] ma non al basale [p=0.085]. Considerandone l’ottimale cut-off predittivo (38 ml/m2) i pazienti a rischio intermedio sono ulteriormente classificabili in intermedio-basso e intermedio-alto. Considerando l'effetto dei 3 principali farmaci che agiscono sulla via della prostaciclina in aggiunta alla duplice terapia di combinazione con inibitori della fosfodiesterasi-5 e antagonisti dell'endotelina, i pazienti trattati con epoprostenolo e.v. hanno ottenuto un maggiore miglioramento rispetto ai pazienti trattati con selexipag; col treprostinil s.c. vi è stata una risposta intermedia. Abbiamo quindi proposto un algoritmo di terapia con selexipag in pazienti a rischio intermedio-basso e con prostanoidi parenterali in pazienti a rischio intermedio-alto.

Trapianto di polmone ed ex-vivo. Esperienza iniziale in due centri trapianti di polmone

Background Il trapianto polmonare rappresenta l'unica soluzione percorribile per l'insufficienza respiratoria end-stage. La principale limitante ad un suo impiego è rappresentata dalla scarsità di polmoni idonei. In questo contesto si colloca il progetto di ricondizionamento ex-vivo. L'implementazione risulta possibile attraverso il ricondizionamento di organi cosiddetti “marginali” o giudicati inizialmente non idonei al trapianto e da donatori a cuore fermo (Donor after Cardiac Death – DCD). Scopo Lo scopo principale del progetto è quello di analizzare i risultati a breve e medio termine del trapianto polmonare effettuato impiegando polmoni sottoposti a procedura di ricondizionamento ex-vivo in due centri trapianti di polmone a basso volume. Materiali e Metodi I dati sono stati raccolti retrospettivamente (da Giugno 2013 per quanto riguarda l’ISMETT e dal 2014 quelli dell’ Ospedale S. Orsola-Malpighi) e in maniera prospettica dal 2019. Risultati Sommando i dati relativi ad entrambi i centri, dal 2013 sono stati eseguiti un totale di 26 procedure di riperfusione. Sei volte i polmoni sono stati giudicati idonei al trapianto al termine con 5 trapianti doppi e un trapianto singolo sinistro. I risultati in termine di sopravvivenza a medio termine sono risultati sovrapponibili a quelli disponibili in letteratura, tuttavia è stato registrato un alto tasso di PGD (Primary Graft Disfunction) di grado 3, da imputare alla patologia di base del ricevente (ipertensione polmonare), che per protocollo di istituto rimane con supporto cardio-respiratorio (ECMO) dopo il trapianto. Conclusioni L’EVLP si conferma in centri di piccolo e medio volume un metodo sicuro ed efficace per implementare in numero di polmoni idonei al trapianto.

Laparoscopic treatment of type 2 diabetes mellitus for patients with a body mass index less than 35

Background Type 2 diabetes mellitus (T2DM) is a common disease with numerous complications. Bariatric surgery is an efficient procedure for controlling T2DM in morbidly obese patients. In T2DM, the incretin effect is either greatly impaired or absent. This study aimed to evaluate the preliminary results from interposing a segment of ileum into the proximal jejunum associated with a sleeve or diverted sleeve gastrectomy to control T2DM in patients with a body mass index (BMI) less than 35 kg/m(2). Methods For this study, 39 patients (16 women and 23 men) underwent two laparoscopic procedures comprising different combinations of ileal interposition into the proximal jejunum via a sleeve or diverted sleeve gastrectomy. The mean age of these patients was 50.3 years (range, 36-66 years). The mean BMI was 30.1 kg/m(2) (range, 23.4-34.9 kg/m(2)). All the patients had a diagnosis of T2DM that had persisted for at least 3 years and evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months. The mean duration of T2DM was 9.3 years (range, 3-22 years). Results The mean operative time was 185 min, and the median hospital stay was 4.3 days. Four major complications occurred in the short term (30-days), and the mortality rate was 2.6%. The mean postoperative follow-up period was 7 months (range, 4-16 months), and the mean percentage of weight loss was 22%. The mean postoperative BMI was 24.9 kg/m(2) (range, 18.9-31.7 kg/m2). An adequate glycemic control was achieved for 86.9% of the patients, and 13.1% had important improvement. The patients whose glycemia was not normalized were using a single oral hypoglycemic agent. No patient needed insulin therapy postoperatively. All the patients except experienced normalization of their cholesterol levels. Targeted triglycerides levels were achieved by 71% of the patients, and hypertension was controlled for 95.8%. Conclusions The laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome. A longer follow-up period is needed.

Comparative study of Botox (R) injection treatment for upper eyelid retraction with 6-month follow-up in patients with thyroid eye disease in the congestive or fibrotic stage

Aim To compare morphometric data of the eyelid fissure and the levator muscle function (LF) before and up to 6 months after transcutaneous injection with five units of Botox (R) in patients with upper lid retraction (ULR) from congestive or fibrotic thyroid eye disease (TED). Methods Twenty-four patients with ULR from TED were submitted to transcutaneous injection of 5 units (0.1 ml) of Botox in one eye only. Patients were divided into two groups: 12 with congestive-stage TED (CG), and 12 with fibrotic-stage TED (FG). Bilateral lid fissure measurements using digital imaging and computer-aided analysis were taken at baseline and at regular intervals 2 weeks, 1 month, 3 months and 6 months after unilateral Botox injection. Mean values taken at different follow-up points were compared for the two groups. Results Most patients experienced marked improvement in ULR, with a mean reduction of 3.81 mm in FG and 3.05 mm in CG. The upper eyelid margin reflex distance, fissure height and total area of exposed interpalpebral fissure were significantly smaller during 1 month in CG and during 3 months in FG. Reduction in LF and in the difference between lateral and medial lid fissure measurements was observed in both groups. The treatment lasted significantly longer in FG than in CG. Conclusions A single 5-unit Botox injection improved ULR, reduced LF and produced an adequate lid contour in patients with congestive or fibrotic TED. The effect lasts longer in patients with fibrotic orbitopathy than in patients with congestive orbitopathy.

Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis.

OBJECTIVES: Gender differences in psychotic disorder have been observed in terms of illness onset and course; however, past research has been limited by inconsistencies between studies and the lack of epidemiological representative of samples assessed. Thus, the aim of this study was to elucidate gender differences in a treated epidemiological sample of patients with first episode psychosis (FEP). METHODS: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics of 661 FEP consecutive patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. RESULTS: Prior to onset of psychosis, females were more likely to have a history of suicide attempts (p=.011) and depression (p=.001). At service entry, females were more likely to have depressive symptoms (p=.007). Conversely, males had marked substance use problems that were evident prior to admission (p<.001) and persisted through treatment (p<.001). At service entry, males also experienced more severe psychopathology (p<.001) and lower levels of functioning (GAF, p=.008; unemployment/not studying p=.004; living with family, p=.003). Treatment non-compliance (p<.001) and frequent hospitalisations (p=.047) were also common for males with FEP. At service discharge males had significantly lower levels of functioning (GAF, p=.008; unemployment/not studying p=.040; living with family, p=.001) compared to females with FEP. CONCLUSIONS: Gender differences are evident in illness course of patients with FEP, particularly with respect to past history of psychopathology and functioning at presentation and at service discharge. Strategies to deal with these gender differences need to be considered in early intervention programs.