Oriented Tailoring of Plastic Antibodies for Prostate Specific Antigen and Application of the Imprinted Material as Ionophore in Potentiometric Detection

Prostate Specific Antigen (PSA) is the biomarker of choice for screening prostate cancer throughout the population, with PSA values above 10 ng/mL pointing out a high probability of associated cancer1. According to the most recent World Health Organization (WHO) data, prostate cancer is the commonest form of cancer in men in Europe2. Early detection of prostate cancer is thus very important and is currently made by screening PSA in men over 45 years old, combined with other alterations in serum and urine parameters. PSA is a glycoprotein with a molecular mass of approximately 32 kDa consisting of one polypeptide chain, which is produced by the secretory epithelium of human prostate. Currently, the standard methods available for PSA screening are immunoassays like Enzyme-Linked Immunoabsorbent Assay (ELISA). These methods are highly sensitive and specific for the detection of PSA, but they require expensive laboratory facilities and high qualify personal resources. Other highly sensitive and specific methods for the detection of PSA have also become available and are in its majority immunobiosensors1,3-5, relying on antibodies. Less expensive methods producing quicker responses are thus needed, which may be achieved by synthesizing artificial antibodies by means of molecular imprinting techniques. These should also be coupled to simple and low cost devices, such as those of the potentiometric kind, one approach that has been proven successful6. Potentiometric sensors offer the advantage of selectivity and portability for use in point-of-care and have been widely recognized as potential analytical tools in this field. The inherent method is simple, precise, accurate and inexpensive regarding reagent consumption and equipment involved. Thus, this work proposes a new plastic antibody for PSA, designed over the surface of graphene layers extracted from graphite. Charged monomers were used to enable an oriented tailoring of the PSA rebinding sites. Uncharged monomers were used as control. These materials were used as ionophores in conventional solid-contact graphite electrodes. The obtained results showed that the imprinted materials displayed a selective response to PSA. The electrodes with charged monomers showed a more stable and sensitive response, with an average slope of -44.2 mV/decade and a detection limit of 5.8X10-11 mol/L (2 ng/mL). The corresponding non-imprinted sensors showed smaller sensitivity, with average slopes of -24.8 mV/decade. The best sensors were successfully applied to the analysis of serum samples, with percentage recoveries of 106.5% and relatives errors of 6.5%.

Cerebral mass lesion due to cytomegalovirus in a patient with AIDS: case report and literature review

Cytomegalovirus (CMV) disease in acquired immunodeficiency syndrome (AIDS) patients most commonly presents as chorioretinitis and gastro-intestinal infection. Neurological involvement due to CMV may cause several clinical presentations: polyradiculitis, myelitis, encephalitis, ventriculo-encephalitis, and mononeuritis multiplex. Rarely, cerebral mass lesion is described. We report a 39 year-old woman with AIDS and previous cerebral toxoplasmosis. She presented with fever, seizures, and vulval ulcers. Her chest X-ray showed multiple lung nodules, and a large frontal lobe lesion was seen in a brain computed tomography scan. She underwent a brain biopsy through a frontal craniotomy, but her condition deteriorated and she died in the first postoperative day. Histopathological studies and immunohistochemistry disclosed CMV disease, and there was no evidence of cerebral toxoplasmosis, bacterial, mycobacterial or fungal infection. CMV disease should be considered in the differential diagnosis of cerebral mass lesion in AIDS patients. High suspicion index, timely diagnostic procedures (surgical or minimally invasive), and proper utilization of prophylactic and therapeutic medication could improve outcome of these patients.

Real-Time Support in the Proposal for Fine-Grained Parallelism in Ada

Presented at Work in Progress Session, IEEE Real-Time Systems Symposium (RTSS 2015). 1 to 3, Dec, 2015. San Antonio, U.S.A..

Abdominal angiostrongyliasis: report of two cases with different clinical presentations

Abdominal angiostrongyliasis is a sporadic infectious disease caused by the nematode Angiostrongylus costaricensis. It usually presents as acute abdomen, secondary to mesenteric ischemia, and pronounced eosinophilia. In some cases its course is insidious and transient, and the diagnosis is suspicious. The disease is confirmed by the detection of A. costaricensis elements in surgical specimen. The treatment is supportive, with avoidance of antihelminthic administration due to a possible erratic migration followed by worsening of the disease. We report two cases, both with intense eosinophilia and serum IgG-ELISA positive to A. costaricensis. The first case presented ileal perforation and was surgically treated. The second one showed hepatic nodules at ultrasound and was only symptomatically treated, evolving to an apparent protracted resolution. These two cases exemplify different clinical forms of the disease, one of them with liver involvement.

Ring enhancing intracranial lesion responding to antituberculous treatment in an HIV-infected patient

Cerebral tuberculomas constitute a major differential diagnosis of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected patients in developing countries. We report the case of a 34-year old woman co-infected with HIV and possible disseminated tuberculosis (hepatitis, lymphadenopathy, and pleural effusion) who presented a large and solitary intracranial mass lesion. Despite extensive diagnostic efforts, including brain, ganglionar, and liver biopsies, no definitive diagnosis was reached. However, a trial with first-line antituberculous drugs led to a significant clinical and radiological improvement. Atypical presentations of cerebral tuberculomas should always be considered in the differential diagnosis of intracranial mass lesions in HIV-infected patients and a trial with antituberculous drugs is a valuable strategy to infer the diagnosis in a subset of patients.

Velas içadas: navigating emotion in a sea of science

Dissertação para obtencão do grau de Mestrado em Arte e Ciência do Vidro

A Communication Intervention for Training Southern European Oncologists to Recognize Psychosocial Morbidity in Cancer. I - Development of the Model and Preliminary Results on Physicians' Satisfaction

BACKGROUND: The detection of psychosocial distress is a significant communication problem in Southern Europe and other countries. Work in this area is hampered by a lack of data. Because not much is known about training aimed at improving the recognition of psychosocial disorders in cancer patients, we developed a basic course model for medical oncology professionals. METHODS: A specific educational and experiential model (12 hours divided into 2 modules) involving formal teaching (ie, journal articles, large-group presentations), practice in small groups (ie, small-group exercises and role playing), and discussion in large groups was developed with the aim of improving the ability of oncologists to detect emotional disturbances in cancer patients (ie, depression, anxiety, and adjustment disorders). RESULTS: A total of 30 oncologists from 3 Southern European countries (Italy, Portugal, and Spain) participated in the workshop. The training course was well accepted by most participants who expressed general satisfaction and a positive subjective perception of the utility of the course for clinical practice. Of the total participants, 28 physicians (93.3%) thought that had they been exposed to this material sooner, they would have incorporated the techniques received in the workshop into their practices; 2 participants stated they would likely have done so. Half of the doctors (n = 15) believed that their clinical communication techniques were improved by participating in the workshop, and the remaining half thought that their abilities to communicate with cancer patients had improved. CONCLUSIONS: This model is a feasible approach for oncologists and is easily applicable to various oncology settings. Further studies will demonstrate the effectiveness of this method for improving oncologists skills in recognizing emotional disorders in their patients with cancer.

NEUROCYSTICERCOSIS IN CHILDREN PRESENTING WITH AFEBRILE SEIZURE: CLINICAL PROFILE, IMAGING AND SERODIAGNOSIS

Neurocysticercosis (NCC) is one of the major causes of childhood seizures in developing countries including India and Latin America. In this study neurological pediatric cases presenting with afebrile seizures were screened for anti-Cysticercus antibodies (IgG) in their sera in order to estimate the possible burden of cysticercal etiology. The study included a total of 61 pediatric afebrile seizure subjects (aged one to 15 years old); there was a male predominance. All the sera were tested using a pre-evaluated commercially procured IgG-ELISA kit (UB-Magiwell Cysticercosis Kit ™). Anti-Cysticercus antibody in serum was positive in 23 of 61 (37.7%) cases. The majority of cases with a positive ELISA test presented with generalized seizure (52.17%), followed by complex partial seizure (26.08%), and simple partial seizure (21.73%). Headaches were the major complaint (73.91%). Other presentations were vomiting (47.82%), pallor (34.78%), altered sensorium (26.08%), and muscle weakness (13.04%). There was one hemiparesis case diagnosed to be NCC. In this study one child without any significant findings on imaging was also found to be positive by serology. There was a statistically significant association found between the cases with multiple lesions on the brain and the ELISA-positivity (p = 0.017). Overall positivity of the ELISA showed a potential cysticercal etiology. Hence, neurocysticercosis should be suspected in every child presenting with afebrile seizure especially with a radio-imaging supportive diagnosis in tropical developing countries or areas endemic for taeniasis/cysticercosis.

Deletions within COL11A1 in Type 2 Stickler Syndrome Detected by Multiplex Ligation - Syndrome Detected by Multiplex Ligation Dependent Probe Amplification (MLPA)

Background: COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the COL11A1, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown. Case presentations: We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone. Conclusion: Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of COL11A1 should include assays capable of detecting both large and small deletions, in addition to exon sequencing.

FIRST REPORT OF CUTANEOUS LEISHMANIASIS CAUSED BY Leishmania (Leishmania) infantum chagasi IN AN URBAN AREA OF RIO DE JANEIRO, BRAZIL

SUMMARY American tegumentary leishmaniasis (ATL) is an infectious disease caused by protozoa of the genus Leishmania, and transmitted by sandflies. In the state of Rio de Janeiro, almost all of the cases of American tegumentary leishmaniasis (ATL) are caused by Leishmania (Viannia) braziliensis, while cases of visceral leishmaniasis (VL) are caused by Leishmania (Leishmania) infantum chagasi. The resurgence of autochthonous VL cases in Rio de Janeiro is related to the geographic expansion of the vector Lutzomyia longipalpis and its ability to adapt to urban areas. We report the first case of leishmaniasis with exclusively cutaneous manifestations caused by L. (L.) infantum chagasi in an urban area of Rio de Janeiro. An eighty-one-year-old woman presented three pleomorphic skin lesions that were not associated with systemic symptoms or visceromegalies. Multilocus enzyme electrophoresis identified L. (L.) infantum chagasi, but direct smear and PCR of bone narrow were negative for Leishmania sp. (suggesting exclusively cutaneous involvement). We discuss the different dermatological presentations of viscerotropic leishmaniasis of the New and Old World, and the clinical and epidemiological importance of the case. Etiologic diagnosis of ATL based upon exclusive clinical criteria may lead to incorrect conclusions. We should be aware of the constant changes in epidemiological patterns related to leishmaniases.

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.

Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

Does direct cash flow presentation help in predicting future operating cash flow?

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Mutations in the MECP2 Gene Are Not a Major Cause of Rett Syndrome-Like or Related Neurodevelopmental Phenotype in Male Patients

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.

Role of sympathetic innervation in obesity

Part of the results presented in this thesis were published in the following reference (DOI 10.1016/j.cell.2015.08.055): Wenwen Zeng*, Roksana M. Pirzgalska*, Mafalda M.A. Pereira, Nadiya Kubasova, Andreia Barateiro, Elsa Seixas, Yi-Hsueh Lu, Albina Kozlova, Henning Voss, Gabriel G. Martins, Jeffrey M. Friedman and Ana I. Domingos. Sympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis. Cell 163, 84-94 (2015). The work was also presented through poster presentations at iMED Conference 6.0 (Lisbon, 2014), Sociedade Portuguesa de Bioquímica Meeting (Coimbra, 2014) and Sociedade Portuguesa de Neurociências Meeting (Póvoa de Varzim, 2015).