Improving the early diagnostic of prostate cancer by multiple biomarker detection with new biosensing devices

Prostate cancer (PCa) is the most common form of cancer in men, in Europe (World Health Organization data). The most recent statistics, in Portuguese territory, confirm this scenario, which states that about 50% of Portuguese men may suffer from prostate cancer and 15% of these will die from this condition. Its early detection is therefore fundamental. This is currently being done by Prostate Specific Antigen (PSA) screening in urine but false positive and negative results are quite often obtained and many patients are sent to unnecessary biopsy procedures. This early detection protocol may be improved, by the development of point-of-care cancer detection devices, not only to PSA but also to other biomarkers recently identified. Thus, the present work aims to screen several biomarkers in cultured human prostate cell lines, serum and urine samples, developing low cost sensors based on new synthetic biomaterials. Biomarkers considered in this study are the following: prostate specific antigen (PSA), annexin A3 (ANXA3), microseminoprotein-beta (MSMB) and sarcosine (SAR). The biomarker recognition may occurs by means of molecularly imprinted polymers (MIP), which are a kind of plastic antibodies, and enzymatic approaches. The growth of a rigid polymer, chemically stable, using the biomarker as a template allows the synthesis of the plastic antibody. MIPs show high sensitivity/selectivity and present much longer stability and much lower price than natural antibodies. This nanostructured material was prepared on a carbon solid. The interaction between the biomarker and the sensing-material produces electrical signals generating quantitative or semi-quantitative data. These devices allow inexpensive and portable detection in point-of-care testing.

The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus

Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.

Is Modernity Multiple?

Fundação para a Ciência e a Tecnologia (FCT), Fundação Millennium bcp

Testing Nelder-Mead based repulsion algorithms for multiple roots of nonlinear systems via a two-level factorial design of experiments

This paper addresses the challenging task of computing multiple roots of a system of nonlinear equations. A repulsion algorithm that invokes the Nelder-Mead (N-M) local search method and uses a penalty-type merit function based on the error function, known as 'erf', is presented. In the N-M algorithm context, different strategies are proposed to enhance the quality of the solutions and improve the overall efficiency. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm.

Project scheduling and cost minimization with multiple availability constrained resources under stochastic conditions

The authors propose a mathematical model to minimize the project total cost where there are multiple resources constrained by maximum availability. They assume the resources as renewable and the activities can use any subset of resources requiring any quantity from a limited real interval. The stochastic nature is inferred by means of a stochastic work content defined per resource within an activity and following a known distribution and the total cost is the sum of the resource allocation cost with the tardiness cost or earliness bonus in case the project finishes after or before the due date, respectively. The model was computationally implemented relying upon an interchange of two global optimization metaheuristics – the electromagnetism-like mechanism and the evolutionary strategies. Two experiments were conducted testing the implementation to projects with single and multiple resources, and with or without maximum availability constraints. The set of collected results shows good behavior in general and provide a tool to further assist project manager decision making in the planning phase.

Are cognitive interventions for multiple sclerosis effective and feasible?

Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR?=?0.81; 95% CI: 0.72-0.92; p?=?0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR?=?1.19; 95% CI: 0.63-2.24; ptrend ?=?0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

Flood pulse and spatial dynamics of mercury in sediments in Puruzinho lake, Brazilian Amazon

The study was conducted in Puruzinho lake (Humaitá, AM) considering seasonal periods of rainy and dry in way to elucidate the flood pulse importance in the deposition, remobilization and distributions of mercury and organic matter in bottom sediments in the Madeira River Basin (Brazilian Amazon). Bottom sediments and soils samples were analyzed for total mercury and organic matter. Mercury concentrations obtained in bottom sediment were 32.20-146.40 ng g-1 and organic matter values were 3.5 - 18.0%. The main region for accumulation of mercury and organic matter was in the central and deepest lake area In the rainy season there was a greater distribution of Hg and organic matter, mainly controlled by means of income of the Madeira river water during flooding, while the predominant process in the dry season was the remobilization of total Hg due to the resuspension of bottom sediments.

Characterization of the oculomotor alterations in inicial phase of Multiple Sclerosis

Dissertação de mestrado em Advanced Optometry

Single line for assembly just-in-sequence multiple models

Programa Doutoral em Líderes para as Indústrias Tecnológicas

Cognitive functioning and efficacy of cognitive intervention in Multiple Sclerosis

Tese de Doutoramento em Psicologia Clínica / Psicologia

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging

BACKGROUND: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. METHOD: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. RESULTS: Mean PWV value for the entire population was 8.4?m/s (men: 8.6?m/s; women: 8.2?m/s; P??10?m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10?m/s 10 years later than men. CONCLUSION: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.

Risk factors for suicide in multiple sclerosis: a case-control study

ABSTRACT Objective To evaluated the prevalence and the suicide risk in a Brazilian sample of patients with multiple sclerosis (MS) and to identify potential factors associated with the risk of suicide. A study was performed with outpatient with MS. The risk of suicide and the presence of psychiatric disorders were assessed by version 5.0 of the Mini-International Neuropsychiatric Interview (MINI). The sample of patients at risk for suicide was matched by sex and age to a control group of patients with MS. Results Eight point three percent of the patients had a past history of attempted suicide, and 8.3% had a current suicide risk, totaling 16.6%. The results of this study suggest that the risk factors associated with suicide in this population are depression, marital status single, widowed or divorced, and lower education level.

Multiple arterial anomalies in the newborn infant. Echocardiographic and angiographic diagnosis

Multiple arterial anomalies characterized by tortuosity and rolling of the pulmonary arteries and aorta were diagnosed on echocardiography in an asymptomatic newborn infant with a phenotype suggesting Ehlers-Danlos syndrome. These changes were later confirmed on angiography, which also showed peripheral vascular abnormalities. The electrocardiogram showed a probable hemiblock of the left anterosuperior branch, and the chest x-ray showed an excavated pulmonary trunk with normal pulmonary flow.