Magnesium – association with inflammation and renal disease in systemic lupus erythematosus

Introduction: Recent studies suggest that magnesium deficiency may play a role in inflammation. In diabetes and cardio-vascular diseases, conditions with a component of chronic inflammation, C–reactive protein levels are higher and associated with low serum magnesium. The objective of this study is to evaluate serum magnesium levels in patients with systemic lupus erythematosus and its potential association with inflammation and renal manifestations. Methods: All patients with systemic lupus erythematosus followed in a Systemic Immune Diseases Unit, from January 2012 until January 2014, were included in this cross sectional analysis. Patients with infection, neoplasia, liver failure and chronic kidney disease (stage > 3) were excluded. Clinical information and laboratory results (serum magnesium, C-reactive protein, erythrocyte sedimentation rate, serum creatinine and spot urine test) were collected. A multivariate analysis was performed to explore possible predictive factors for hypomagnesaemia. Results: One hundred and two patients were included (94.1% female, 21-86 years). 33.4% had hypertension, 8.8% had diabetes and 20.6% had hypomagnesaemia (< 1.8mg/dL). There were no significant differences between the inflammatory parameters of patients with hypomagnesaemia or normomagnesaemia. Serum magnesium was significantly lower with increasing comorbidities (p = 0.01). Leukocyturia was significantly higher in the hypomagnesaemia group (p = 0.03) and haematuria had a negative correlation with serum magnesium (-0.23, p < 0.05). Multivariate analysis showed that patients with hypertension and diabetes had higher risk of hypomagnesaemia: OR 42.29 (95% CI, 1.43-1249.31). Leukocyturia was also individually and independently associated with hypomagnesaemia: OR 8.37 (95% CI, 1.40-49.97). Conclusion: The presence of hypomagnesaemia in our patients with systemic lupus erythematosus was high. There was no association between the levels of serum magnesium and the inflammatory parameters. Increasing comorbidities and leukocyturia were independent predictors of lower serum magnesium. Finally, the association of leukocyturia and haematuria with lower serum magnesium may suggest a relationship with a higher disease activity.

ASSOCIATION BETWEEN SMOKING, CRACK COCAINE ABUSE AND THE DISCONTINUATION OF COMBINATION ANTIRETROVIRAL THERAPY IN RECIFE, PERNAMBUCO, BRAZIL

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.

Mecanismos de inflamação brônquica resultantes da exposição a factores ambientais

RESUMO Tratando-se a asma de uma doença respiratória, desde há várias décadas que tem sido abordada a hipótese de que factores ambientais, nomeadamente os relacionados com a qualidade do ar inalado, possam contribuir para o seu agravamento. Para além dos aeroalergenos, outros factores ambientais como a poluição atmosférica estarão associados às doenças respiratórias. O ar respirado contém uma variedade de poluentes atmosféricos, provenientes quer de fontes naturais quer de origem antropogénica, nomeadamente de actividades industriais, domésticas ou das emissões de veículos. Estes poluentes, tradicionalmente considerados como um problema de foro ambiental, têm sido cada vez mais encarados como um problema de saúde pública. Também a qualidade do ar interior, tem sido associada a queixas respiratórias, não só em termos ocupacionais mas também em exposições domésticas. Dentro dos principais poluentes, encontramos a matéria particulada (como as PM10), o O3, NO2, e os compostos orgânicos voláteis (COVs). Se é verdade que os três primeiros têm como principais fontes de exposição a combustão fóssil associada aos veículos automóveis, já os COVs (como o benzeno, tolueno, xileno, etilbenzeno e formaldeído) são poluentes mais característicos do ar interior. Os mecanismos fisiopatológicos subjacentes à agressão dos poluentes do ar não se encontram convenientemente esclarecidos. Pensa-se que após a sua inalação, induzam um grau crescente de stress oxidativo que será responsável pelo desenvolvimento da inflamação das vias aéreas. A progressão do stress oxidativo e da inflamação, associarse- ão posteriormente a lesão local (pulmonar) e sistémica. Neste trabalho pretendeu-se avaliar os efeitos da exposição individual a diversos poluentes, do ar exterior e interior, sobre as vias aéreas, recorrendo a parâmetros funcionais, inflamatórios e do estudo do stress oxidativo. Neste sentido, desenvolveu-se um estudo de painel na cidade de Viseu, em que foram acompanhadas durante 18 meses, 51 crianças com história de sibilância, identificadas pelo questionário do estudo ISAAC. As crianças foram avaliadas em quatro Visitas (quatro medidas repetidas), através de diversos exames, que incluíram execução de espirometria com broncodilatação, medição ambulatória do PEF, medição de FENO e estudo do pH no condensado brônquico do ar exalado. O estudo dos 8-isoprostanos no condensado brônquico foi efectuado somente em duas Visitas, e o do doseamento de malonaldeído urinário somente na última Visita. Para além da avaliação do grau de infestação de ácaros do pó do colchão, para cada criança foi calculado o valor de exposição individual a PM10, O3, NO2, benzeno, tolueno, xileno, etilbenzeno e formaldeído, através de uma complexa metodologia que envolveu técnicas de modelação associadas a medições directas do ar interior (na casa e escola da criança) e do ar exterior. Para a análise de dados foram utilizadas equações de estimação generalizadas com uma matriz de correlação de trabalho uniforme, com excepção do estudo das associações entre poluentes, 8-isoprostanos e malonaldeído. Verificou-se na análise multivariável a existência de uma associação entre o agravamento dos parâmetros espirométricos e a exposição aumentada a PM10, NO2, benzeno, tolueno e etilbenzeno. Foram também encontradas associações entre diminuição do pH do EBC e exposição crescente a PM10, NO2, benzeno e etilbenzeno e associações entre valores aumentados de FENO e exposição a etilbenzeno e tolueno. O benzeno, o tolueno e o etilbenzeno foram associados com maior recurso a broncodilatador nos 6 meses anteriores à Visita e o tolueno com deslocações ao serviço de urgência. Os resultados dos modelos de regressão que incluíram o efeito do poluente ajustado para o grau de infestação de ácaros do pó foram, de uma forma geral, idênticos ao da análise multivariável anterior, com excepção das associações para com o FENO. Nos modelos de exposição com dois poluentes, com o FEV1 como variável resposta, somente o benzeno persistiu com significado estatístico. No modelo com dois poluentes tendo o pH do EBC como variável resposta, somente persistiram as PM10. Os 8-isoprostanos correlacionaram-se com alguns COVs, designadamente etilbenzeno, xileno, tolueno e benzeno. Os valores de malonaldeído urinário não se correlacionaram com os valores de poluentes. Verificou-se no entanto que de uma forma geral, e em particular mais uma vez para os COVs, as crianças mais expostas a poluentes, apresentaram valores superiores de malonaldeído na urina. Verificou-se que os poluentes do ar em geral, e os COVs em particular, se associaram com uma deterioração das vias aéreas. A exposição crescente a poluentes associou-se não só com obstrução brônquica, mas também com FENO aumentado e maior acidez das vias aéreas. A exposição crescente a COVs correlacionou-se com um maior stress oxidativo das vias aéreas (medido pelos 8-isoprostanos). As crianças com exposição superior a COVs apresentaram maiores valores de malonaldeído urinário. Este trabalho sugere uma associação entre exposição a poluentes, inflamação das vias aéreas e stress oxidativo. Vem reforçar o interesse dos poluentes do ar, nomeadamente os associados a ambientes interiores, frequentemente esquecidos e que poderão ser explicativos do agravamento duma criança com sibilância.-----------ABSTRACT: Asthma is a chronic respiratory disease that could be influenced by environmental factors, as allergens and air pollutants. The air breathed contains a diversity of air pollutants, both from natural or anthropogenic sources. Atmospheric pollution, traditionally considered an environmental problem, is nowadays looked as an important public health problem. Indoor air pollutants are also related with respiratory diseases, not only in terms of occupational exposures but also in domestic activities. Particulate matter (such as PM10), O3, NO2 and volatile organic compounds (VOCs) are the main air pollutants. The main source for PM10, O3, NO2 exposure is traffic exhaust while for VOCs (such as benzene, toluene, xylene, ethylbenzene and phormaldehyde) the main sources for exposure are located in indoor environments. The pathophysiologic mechanisms underlying the aggression of air pollutants are not properly understood. It is thought that after inhalation, air pollutants could induce oxidative stress, which would be responsible for airways inflammation. The progression of oxidative stress and airways inflammation, would contribute for the local and systemic effects of the air pollutants. The present study aimed to evaluate the effects of individual exposure to various pollutants over the airways, through lung function tests, inflammatory and oxidative stress biomarkers. In this sense, we developed a panel study in the city of Viseu, that included 51 children with a history of wheezing. Those children that were identified by the ISAAC questionnaire, were followed for 18 months. Children were assessed four times (four repeated measures) through the following tests: spirometry with bronchodilation test, PEF study, FENO evaluation and exhaled breath condensate pH measurement. 8-isoprostane in the exhaled breath condensate were also measured but only in two visits. Urinary malonaldehyde measurement was performed only in the last visit. Besides the assessment of the house dust mite infestation, we calculated for each child the value of individual exposure to a wide range of pollutants: PM10, O3, NO2, benzene, toluene, xylene, ethyl benzene and formaldehyde. This strategy used a complex methodology that included air pollution modelling techniques and direct measurements indoors (homes and schools) and outdoors. Generalized estimating equations with an exchangeable working correlation matrix were used for the analysis of the data. Exceptions were for the study of associations between air pollutants, malonaldehyde and 8-isoprostanes. In the multivariate analysis we found an association between worsening of spirometric outcomes and increased exposure to PM10, NO2, benzene, toluene and ethylbenzene. In the multivariate analysis we found also negative associations between EBC pH and exposure to PM10, NO2, benzene, ethylbenzene and positive associations between FENO and exposure to ethylbenzene and toluene. Benzene, toluene and ethylbenzene were associated with increased use of bronchodilator in the 6 months prior to the visit and toluene with emergency department visits. Results of the regression models that included also the effect of the pollutant adjusted for the degree of infestation to house dust mites, were identical to the previous models. Exceptions were for FENO associations. In the two-pollutant models, with the FEV1 as dependent variable, only benzene persisted with statistical significance. In the two pollutant model with pH of EBC as dependent variable, only PM10 persisted. 8-isoprostanes were well correlated with some VOCs, namely with ethylbenzene, xylene, toluene and benzene. Urinary malonaldehyde did not present any correlation with air pollutants exposure. However, those children more exposed to air pollutants (namely to VOCs), presented higher values of malonaldehyde. It was found that air pollutants in general, and namely VOCs, were associated with deterioration of the airways. The increased exposure to air pollutants was associated not only with airways obstruction, but also with increased FENO and higher acidity of the airways. The increased exposure to VOCs was correlated with increased airways oxidative stress (measured by 8-isoprostane). Children with higher levels of exposure to VOCs had higher values of urinary malonaldehyde. This study suggests a relation between air pollution, airways inflammation and oxidative stress. It suggests also that attention should be dedicated to air quality as air pollutants could cause airways deterioration.

LACK OF ASSOCIATION BETWEEN HERPESVIRUS DETECTION IN SALIVA AND GINGIVITIS IN HIV‑INFECTED CHILDREN

The aims of this study were to compare the detection of human herpesviruses (HHVs) in the saliva of HIV-infected and healthy control children, and to evaluate associations between viral infection and gingivitis and immunodeficiency. Saliva samples were collected from 48 HIV-infected and 48 healthy control children. Clinical and laboratory data were collected during dental visits and from medical records. A trained dentist determined gingival indices and extension of gingivitis. Saliva samples were tested for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by nested polymerase chain reaction assays. Thirty-five HIV-infected and 16 control children had gingivitis. Seventeen (35.4%) HIV-infected children and 13 (27%) control children were positive for HHVs. CMV was the most commonly detected HHV in both groups (HIV-infected, 25%; control, 12.5%), followed by HSV-1 (6.2% in both groups) and HSV-2 (HIV-infected, 4.2%; control, 8.3%). The presence of HHVs in saliva was not associated with the presence of gingivitis in HIV-1-infected children (p = 0.104) or healthy control children (p = 0.251), or with immunosuppression in HIV-infected individuals (p = 0.447). Gingivitis was correlated with HIV infection (p = 0.0001). These results suggest that asymptomatic salivary detection of HHVs is common in HIV-infected and healthy children, and that it is not associated with gingivitis.

Achondroplasia and Down’s Syndrome – Case Report of a Rare Association

The association of achondroplasia and Down’s syndrome is very rare and only five cases have been reported in the literature so far. These two genetic alterations have overlapping features such as short stature, developmental delay or hypotonia that complicate management and follow up. We report the case of a girl that is unique since she was born from a mother with achondroplasia and a healthy father. Achondroplasia was dominantly inherited from the mother but at birth she had features of Down’s syndrome as well, confirmed later by kariotype. We review her evolution regarding physical health, cognitive problems and adaptive behavior during her eight years of life. To our knowledge this is the first report of the combination of both disorders in which the achondroplasia was inherited and not a “de novo” mutation. We address the problems resulting from the additional burden of having two disorders, and how they can be improved, aiming to help others in the future to deal with these cases.

Kitchen robot prod. line development. Proj. of Bowden cables cutting and thermal forming machine.

This document presents particular description of work done during student’s internship in PR Metal company realized as ERASMUS PROJECT at ISEP. All information including company’s description and its structure, overview of the problems and analyzed cases, all stages of projects from concept to conclusion can be found here. Description of work done during the internship is divided here into two pieces. First part concerns one activities of the company which is robotic chefs (kitchen robot) production line. Work, that was done for development of this line involved several tasks, among them: creating a single-worker montage station for screwing robots housing’s parts, improve security system for laser welding chamber, what particularly consists in designing automatically closing door system with special surface, that protects against destructive action of laser beam, test station for examination of durability of heating connectors, solving problem with rotors vibrations. Second part tells about main task, realized in second half of internship and stands a complete description of machine development and design. The machine is a part of car handle latch cable production line and its tasks are: cutting cable to required length and hot-forming plastic cover for further assembly needs.

On-line system for faults detection in induction motors based on PCA

Dissertation to obtain the degree of Master in Electrical and Computer Engineering

DENGUE DURING PREGNANCY: ASSOCIATION WITH LOW BIRTH WEIGHT AND PREMATURITY

The aim of this study was to evaluate the effects of dengue virus infection during pregnancy and its correlation with low birth weight, prematurity, and asphyxia. A non-concurrent cohort study reveals the association of dengue during pregnancy with prematurity and low birth weight, when birth occurred during the maternal-fetal viremia period (p = 0.016 and p < 0.0001, respectively).

Association of Intestinal Malrotation and Bochdalek Hernia in an Adult: a Case Report

Background Late presentations of congenital diaphragmatic hernia are rare and differ from the classic neonatal presentation. The association with other congenital malformations in children, mainly intestinal malrotation, is well documented. The diagnosis of this association in adults is very rare, and depends on a high degree of suspicion. Case presentation We report a case of a 50-year-old female Caucasian patient with a previous history of intestinal malrotation diagnosed in adolescence and treated conservatively. She was referred to the hospital with signs and symptoms of intestinal obstruction. The patient undertook computed tomography that confirmed small bowel obstruction with no obvious cause, and a right subphrenic abscess with right empyema was also present. An exploratory laparotomy was performed that revealed an intestinal malrotation associated with a right gangrenous and perforated Bochdalek hernia. Resection of the affected small bowel, closure of the Bochdalek foramen and the Ladd procedure were carried out. Conclusion This case shows a rare association of two rare conditions in adults, and highlights the challenge in reaching the diagnosis and management options.

PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS

Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation.

CO2 Concentration in Day Care Centres is Related to Wheezing in Attending Children

Poor ventilation at day care centres (DCCs) was already reported, although its effects on attending children are not clear. This study aimed to evaluate the association between wheezing in children and indoor CO2 (a ventilation surrogate marker) in DCC and to identify behaviours and building characteristics potentially related to CO2. In phase I, 45 DCCs from Lisbon and Oporto (Portugal) were selected through a proportional stratified random sampling. In phase II, 3 months later, 19 DCCs were further reassessed after cluster analysis for the greatest difference comparison. In both phases, children’s respiratory health was assessed by ISAAC-derived questionnaires. Indoor CO2 concentrations and building characteristics of the DCC were evaluated in both phases, using complementary methods. Mixed effect models were used to analyze the data. In phase I, which included 3,186 children (mean age 3.1±1.5 years), indoor CO2 concentration in the DCC rooms was associated with reported wheezing in the past 12months (27.5 %) (adjusted odds ratio (OR) for each increase of 200 ppm 1.04, 95 % CI 1:01 to 1:07). In phase II, the association in the subsample of 1,196 children seen in 19 out of the initial 45 DCCs was not significant (adjusted OR 1.02, 95 % CI 0.96 to 1.08). Indoor CO2 concentration was inversely associated with the practices of opening Windows and internal doors and with higher wind velocity. A positive trend was observed between CO2 and prevalence of reported asthma (4.7 %). Conclusion: Improved ventilation is needed to achieve a healthier indoor environment in DCC.

Environment and Health in Children Day Care Centres (ENVIRH) - Study Rationale and Protocol

Background: Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. Methods --- study design: This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children’s respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. Results: In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children’s health. A building ventilation model will also be developed. Discussion: This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC.

Gene Expression Profiling and Association Studies Implicate the Neuregulin Signaling Pathway in Behçet's Disease Susceptibility

Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene–gene interactions. These association findings support a role for the EGF/ErbB signaling pathway inBD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.

Derivation and consistency checking of models in early software product line engineering

Dissertação para obtenção do Grau de Doutor em Engenharia Informática