Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

^a Introduction Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. Methods This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. Results In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. Conclusions The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

Evaluation of the cytokine mannose-binding lectin as a mediator of periportal fibrosis progression in patients with schistosomiasis

INTRODUCTION : We hypothesized higher mannose-binding lectin level and classic factors (i.e., age, sex, alcohol consumption, exposure, and specific treatment) are associated with the severity of periportal fibrosis in schistosomiasis. METHODS : This cross-sectional study involved 79 patients infected with Schistosoma mansoni with severe or mild/moderate periportal fibrosis. Serum concentrations of mannose-binding lectin were obtained by enzyme-linked immunosorbent assay (ELISA). RESULTS: Higher serum level of mannose-binding lectin was significantly associated with advanced periportal fibrosis. CONCLUSIONS: Mannose-binding lectin may contribute to liver pathology in schistosomiasis and may represent a risk factor for advanced periportal fibrosis in the Brazilian population studied.

Arboviral diseases in the Western Brazilian Amazon: a perspective and analysis from a tertiary health & research center in Manaus, State of Amazonas

The Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), located in Manaus, the capital of the State of Amazonas (Western Brazilian Amazon), is a pioneering institution in this region regarding the syndromic surveillance of acute febrile illness, including arboviral infections. Based on the data from patients at the FMT-HVD, we have detected recurrent outbreaks in Manaus by the four dengue serotypes in the past 15 years, with increasing severity of the disease. This endemicity has culminated in the simultaneous circulation of all four serotypes in 2011, the first time this has been reported in Brazil. Between 1996 and 2009, 42 cases of yellow fever (YF) were registered in the State of Amazonas, and 71.4% (30/42) were fatal. Since 2010, no cases have been reported. Because the introduction of the yellow fever virus into a large city such as Manaus, which is widely infested by Aedes mosquitoes, may pose a real risk of a yellow fever outbreak, efforts to maintain an appropriate immunization policy for the populace are critical. Manaus has also suffered silent outbreaks of Mayaro and Oropouche fevers lately, most of which were misdiagnosed as dengue fever. The tropical conditions of the State of Amazonas favor the existence of other arboviruses capable of producing human disease. Under this real threat, represented by at least 4 arboviruses producing human infections in Manaus and in other neighboring countries, it is important to develop an efficient public health surveillance strategy, including laboratories that are able to make proper diagnoses of arboviruses.

Reflux esophagitis and gastroesophageal reflux disease: a cross-sectional study of gastroesophageal reflux disease patients by age group

The purpose of this study was to explore the relationship between the intensity of acid reflux and severity of esophageal tissue damage in a cross-sectional study of patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with were selected in accordance with the strict 24-hour ambulatory esophageal pHmetry (24h-pHM) criteria and distributed into three age groups: Group A: 14 - 24 years of age. Group B: 25 - 54; and Group C: 55 - 64. The 24h-pHM was carried out in accordance with DeMeester standardization, and the Savary-Miller classification for the diagnosis of reflux esophagitis was used. The groups were similar in 24h-pHM parameters (p > 0.05), having above normal values. For the study group as a whole, there was no correlation between age group and intensity of acid reflux, and there was no correlation between intensity of acid reflux and severity of esophageal tissue damage. However, when the same patients were sub-grouped in accordance with the depth of their epithelial injury and then distributed into age groups, there was a significant difference in esophagitis without epithelial discontinuity. Younger patients had less epithelial damage than older patients. Additionally, although there was a significant progression from the least severe to the moderate stages of epithelial damage among the age groups, there was no apparent difference among the age groups in the distribution between the moderate stages and most severe stages. The findings support the conclusion that the protective response of individuals to acid reflux varies widely. Continued aggression by acid reflux appears to lead to the exhaustion of individual mechanisms of epithelial protection in some patients, but not others, regardless of age or duration of the disease. Therefore, the diagnosis and follow-up of GERD should include both measurements of the quantity of refluxed acid and an assessment of the damage to the esophageal epithelium.

Critical analysis of the allocation policy for liver transplantation in Brazil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of São Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Saúde de São Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.

Systemic hypertension, diabetes mellitus, and dyslipidemia in relation to body mass index: evaluation of a Brazilian population

OBJECTIVE: To determine the prevalence of systemic hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia in a Brazilian population in relation to body mass index. METHOD: Retrospective evaluation of 1213 adults (mean age: 45.2 ± 12.8; 80.6% females) divided into groups according to body mass index [normal (18.5 - 24.4 kg/m²); overweight (25 - 29.9 kg/m²); grade 1 obesity (30 - 34.9 kg/m²); grade 2 obesity (35 - 39.9 kg/m²), and grade 3 obesity (> 40 kg/m²)]. The prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia were analyzed in each group. The severity of cardiovascular risk was determined. High-risk patients were considered those reporting 2 or more of the following factors: systemic hypertension, HDL < 35 mg/dL, total cholesterol > 240 mg/dL, triglycerides > 200 mg/dL when HDL < 35 mg/dL, and glycemia > 126 mg/dL. Moderate-risk patients were those reporting 2 or more of the following factors: systemic hypertension, HDL < 45, triglycerides > 200 mg/dL, and total cholesterol > 200 mg/dL. RESULTS: The prevalence of systemic hypertension, diabetes mellitus, hypertriglyceridemia, and low HDL-cholesterol levels increased along with weight, but the prevalence of hypercholesterolemia did not. The odds ratio adjusted for gender and age, according to grade of obesity compared with patients with normal weight were respectively 5.9, 8.6, and 14.8 for systemic hypertension, 3.8, 5.8, and 9.2 for diabetes mellitus and 1.2, 1.3, and 2.6 for hypertriglyceridemia. We also verified that body mass index was positively related to cardiovascular high risk (P < .001) CONCLUSION: In our population, cardiovascular risk increased along with body mass index.

Bethanecol chloride for treatment of clomipramine-induced orgasmic dysfunction in males

PURPOSE: To investigate whether bethanecol chloride may be an alternative for the clinical management of clomipramine-induced orgasmic dysfunction, reported to occur in up to 96% of male users. METHODS: In this study, 12 fully remitted panic disorder patients, complaining of severe clomipramine-induced ejaculatory delay, were randomly assigned to either bethanecol chloride tablets (20 mg, as needed) or placebo in a randomized, double-blind, placebo-controlled, two-period crossover study. A visual analog scale was used to assess severity of the orgasmic dysfunction. RESULTS: A clear improvement was observed in the active treatment period. No placebo or carry-over effects were observed. CONCLUSION: These findings suggest that bethanecol chloride given 45 minutes before sexual intercourse may be useful for clomipramine-induced orgasmic dysfunction in males.

Application of wavelets to the study of political history

\The idea that social processes develop in a cyclical manner is somewhat like a `Lorelei'. Researchers are lured to it because of its theoretical promise, only to become entangled in (if not wrecked by) messy problems of empirical inference. The reasoning leading to hypotheses of some kind of cycle is often elegant enough, yet the data from repeated observations rarely display the supposed cyclical pattern. (...) In addition, various `schools' seem to exist which frequently arrive at di erent conclusions on the basis of the same data." (van der Eijk and Weber 1987:271). Much of the empirical controversies around these issues arise because of three distinct problems: the coexistence of cycles of di erent periodicities, the possibility of transient cycles and the existence of cycles without xed periodicity. In some cases, there are no reasons to expect any of these phenomena to be relevant. Seasonality caused by Christmas is one such example (Wen 2002). In such cases, researchers mostly rely on spectral analysis and Auto-Regressive Moving-Average (ARMA) models to estimate the periodicity of cycles.1 However, and this is particularly true in social sciences, sometimes there are good theoretical reasons to expect irregular cycles. In such cases, \the identi cation of periodic movement in something like the vote is a daunting task all by itself. When a pendulum swings with an irregular beat (frequency), and the extent of the swing (amplitude) is not constant, mathematical functions like sine-waves are of no use."(Lebo and Norpoth 2007:73) In the past, this di culty has led to two di erent approaches. On the one hand, some researchers dismissed these methods altogether, relying on informal alternatives that do not meet rigorous standards of statistical inference. Goldstein (1985 and 1988), studying the severity of Great power wars is one such example. On the other hand, there are authors who transfer the assumptions of spectral analysis (and ARMA models) into fundamental assumptions about the nature of social phenomena. This type of argument was produced by Beck (1991) who, in a reply to Goldstein (1988), claimed that only \ xed period models are meaningful models of cyclic phenomena".We argue that wavelet analysis|a mathematical framework developed in the mid-1980s (Grossman and Morlet 1984; Goupillaud et al. 1984) | is a very viable alternative to study cycles in political time-series. It has the advantage of staying close to the frequency domain approach of spectral analysis while addressing its main limitations. Its principal contribution comes from estimating the spectral characteristics of a time-series as a function of time, thus revealing how its di erent periodic components may change over time. The rest of article proceeds as follows. In the section \Time-frequency Analysis", we study in some detail the continuous wavelet transform and compare its time-frequency properties with the more standard tool for that purpose, the windowed Fourier transform. In the section \The British Political Pendulum", we apply wavelet analysis to essentially the same data analyzed by Lebo and Norpoth (2007) and Merrill, Grofman and Brunell (2011) and try to provide a more nuanced answer to the same question discussed by these authors: do British electoral politics exhibit cycles? Finally, in the last section, we present a concise list of future directions.

Seismic evaluation of environmentally degraded FRP-strengthened masonry walls

Fiber Reinforced Polymers (FRPs) have been extensively used for externally bonded reinforcement of masonry structures during the last years. Available information shows that FRPs can significantly improve the seismic performance of masonry elements without altering their structural mass. However, the durability and long-term performance of the strengthened elements are not clearly known yet. Recent experimental results show that environmental conditions can lead to degradation of the bond between FRP and masonry and FRP delaminations. But the effect of these local degradation mechanisms on the global structural response is not studied yet. This paper is therefore aimed at numerically investigating the effect of environmental degradation on the global performance of strengthened masonry walls. The nonlinear behavior of masonry walls strengthened with FRP composites is initially simulated with the aim of a FE package. The adopted numerical modeling strategy is verified by comparison of numerical and experimental results. The model, once validated, is used for investigating the effect of materials and bond degradation on the global behavior and failure modes of strengthened walls. The effect of strengthening scheme on the long-term performance of strengthened walls is also investigated. The degradation data are taken from experimental tests previously performed by the authors. The numerical results show that the effect of local material degradation on the global response of strengthened walls depends on the strengthening schemes, and severity of the environmental conditions. Moreover, environmental induced degradations and FRP delaminations can lead to change of expected failure modes in the strengthened elements. These observations, that are usually neglected at the design stage, can be critical in the long-term performance of strengthened structures.

A case study of product usability of a pelvic device used by children with neuromotor impairments

On assistive technology targeted for people with activity limitations and participation, usability issues becomes an essential tool to ensure that the product has the appropriate ergonomics characteristics, in other words, ensure that it fits the specific user´s needs. The aim of this study was to analyze the usability of an adaptive seating device for children with neuromotor impairments, by using kinematic indicators of the reaching movement. The study sample consisted of 13 children with associated neurologic conditions. The tests were developed by using a wooden bench height adjustable, integrated with the adaptive seating device under study, and a system to capture three-dimensional image, called Qualisys Track Manager. The following reaching kinematics variables were measured: maximum reaching velocity, movement duration, index of curvature, and unit movements. It was found that the use of the adaptive seating device had a positive impact on upper limb function in children with neuromotor impairments. It was also noticed an improvement in the reaching movement kinematics, which was statistical significant for the index of curvature and unit movements. As main conclusions, it is possible to point out some positive effects that the product under study seems to have on users' movements, such as the improved movement quality of the upper limb, which could mean a better postural adjustments and higher trunk postural control. By identifying new measures of usability in terms of effectiveness and efficiency for the analyzeddevice, the results obtained may serve also as performance indicators, providing new data that may help to improve the product and eventually modifying it, in order to turn it more compatible with the needs of the considered target population.

Mothers' beliefs concerning severity and need for intervention in child maltreatment

Dissertação de mestrado integrado em Psicologia Clínica e da Saúde

Assessing the application of polypropylene multifilament yarns in brain phantoms

The currently available clinical imaging methods do not provide highly detailed information about location and severity of axonal injury or the expected recovery time of patients with traumatic brain injury [1]. High-Definition Fiber Tractography (HDFT) is a novel imaging modality that allows visualizing and quantifying, directly, the degree of axons damage, predicting functional deficits due to traumatic axonal injury and loss of cortical projections. This imaging modality is based on diffusion technology [2]. The inexistence of a phantom able to mimic properly the human brain hinders the possibility of testing, calibrating and validating these medical imaging techniques. Most research done in this area fails in key points, such as the size limit reproduced of the brain fibers and the quick and easy reproducibility of phantoms [3]. For that reason, it is necessary to develop similar structures matching the micron scale of axon tubes. Flexible textiles can play an important role since they allow producing controlled packing densities and crossing structures that match closely the human crossing patterns of the brain. To build a brain phantom, several parameters must be taken into account in what concerns to the materials selection, like hydrophobicity, density and fiber diameter, since these factors influence directly the values of fractional anisotropy. Fiber cross-section shape is other important parameter. Earlier studies showed that synthetic fibrous materials are a good choice for building a brain phantom [4]. The present work is integrated in a broader project that aims to develop a brain phantom made by fibrous materials to validate and calibrate HDFT. Due to the similarity between thousands of hollow multifilaments in a fibrous arrangement, like a yarn, and the axons, low twist polypropylene multifilament yarns were selected for this development. In this sense, extruded hollow filaments were analysed in scanning electron microscope to characterize their main dimensions and shape. In order to approximate the dimensional scale to human axons, five types of polypropylene yarns with different linear density (denier) were used, aiming to understand the effect of linear density on the filament inner and outer areas. Moreover, in order to achieve the required dimensions, the polypropylene filaments cross-section was diminished in a drawing stage of a filament extrusion line. Subsequently, tensile tests were performed to characterize the mechanical behaviour of hollow filaments and to evaluate the differences between stretched and non-stretched filaments. In general, an increase of the linear density causes the increase in the size of the filament cross section. With the increase of structure orientation of filaments, induced by stretching, breaking tenacity increases and elongation at break decreases. The production of hollow fibers, with the required characteristics, is one of the key steps to create a brain phantom that properly mimics the human brain that may be used for the validation and calibration of HDFT, an imaging approach that is expected to contribute significantly to the areas of brain related research.

Analysis of exploratory eye movements in patients with schizophrenia during visual scanning of projective tests' figures

OBJECTIVE: Compare pattern of exploratory eye movements during visual scanning of the Rorschach and TAT test cards in people with schizophrenia and controls. METHOD: 10 participants with schizophrenia and 10 controls matched by age, schooling and intellectual level participated in the study. Severity of symptoms was evaluated with the Positive and Negative Syndrome Scale. Test cards were divided into three groups: TAT cards with scenes content, TAT cards with interaction content (TAT-faces), and Rorschach cards with abstract images. Eye movements were analyzed for: total number, duration and location of fixation; and length of saccadic movements. RESULTS: Different pattern of eye movement was found, with schizophrenia participants showing lower number of fixations but longer fixation duration in Rorschach cards and TAT-faces. The biggest difference was observed in Rorschach, followed by TAT-faces and TAT-scene cards. CONCLUSIONS: Results suggest alteration in visual exploration mechanisms possibly related to integration of abstract visual information.

Clozapine-induced severe eosinophilia: report of a case with good outcome

INTRODUCTION: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. METHODS: Case report and literature review. RESULTS: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils began to increase. Drug titration was stopped, but eosinophils counts continued to rise up, reaching the mark of 5200/mm³. Due to severity of psychotic symptoms and to the good response obtained with clozapine, we decided to investigate organs involvement before withdrawing the medication. As the patient had no organs involvement, clozapine was maintained and one month after eosinophils peak, it was already normalized. CONCLUSION: Eosinophilia should not necessarily lead to clozapine's withdrawal. Patients who present eosinophilia must be at rigorous observation for organs involvement, and if there is no such involvement, clozapine might be maintained, considering the possible benign and transitory nature of the eosinophils count elevation.

Presence of dual diagnosis between users and non-users of licit and illicit drugs in Brazil

ABSTRACT Objective Investigate the occurrence of dual diagnosis in users of legal and illegal drugs. Methods It is an analytical, cross-sectional study with a quantitative approach, non-probabilistic intentional sampling, carried out in two centers for drug addiction treatment, by means of individual interviews. A sociodemographic questionnaire, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Mini-International Neuropsychiatric Interview (MINI) were used. Results One hundred and ten volunteers divided into abstinent users (group 1), alcoholics (group 2) and users of alcohol and illicit drugs (group 3). The substances were alcohol, tobacco, crack and marijuana. A higher presence of dual diagnosis in group 3 (71.8%) was observed, which decreased in group 2 (60%) and 37.1% of drug abstinent users had psychiatric disorder. Dual diagnosis was associated with the risk of suicide, suicide attempts and the practice of infractions. The crack consumption was associated with the occurrence of major depressive episode and antisocial personality disorder. Conclusion It was concluded that the illicit drug users had a higher presence of dual diagnosis showing the severity of this clinical condition. It is considered essential that this clinical reality is included in intervention strategies in order to decrease the negative effects of consumption of these substances and provide better quality of life for these people.