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  • Prevalence of Portuguese Children Exposed to Secondhand Smoke at Home and in the Car
    Publication . Precioso, J; Rocha, V; Sousa, I; Araújo, AC; Machado, JC; Antunes, H
    Introduction: Children’s exposure to secondhand smoke is a cause of serious health problems and infant morbidity. This is the first nationally representative study conducted in Portugal to describe the prevalence of children exposed to secondhand smoke at home and in the car. Material and Methods: This is a descriptive cross-sectional study with a representative sample of 2396 Portuguese children aged 0 to 9 years old, stratified by age and administrative region NUTS II. Questionnaires were administered between January and September 2016. Results: Results showed that 6.1% of mothers and 11.2% of fathers reported smoking at home. It was found that 4.5% of mothers and 8.3% of fathers reported smoking in the car. Results also showed that 5.4% of children were double exposed to secondhand smoke at home and in the car. Children whose parents were smokers and had a lower level of education were more exposed to secondhand smoke at home. Discussion: Children’s exposure to secondhand smoke has been decreasing in Portugal. Parental smoking and a low educational level were risk factors for children’s exposure to secondhand smoke at home. Conclusion: The main source of children’s exposure to secondhand smoke is parental smoking. As such, it is crucial to implement effective measures to control parental smoking. It is necessary to promote smoking cessation among parents and to ban smoking inside the car.
  • Characterization of a large cluster of HIV-1 A1 infections detected in Portugal and connected to several Western European countries
    Publication . Araújo, PM; Carvalho, A; Pingarilho, M; Abecasis, AB; Osório, NS
    HIV-1 subtypes associate with differences in transmission and disease progression. Thus, the existence of geographic hotspots of subtype diversity deepens the complexity of HIV-1/AIDS control. The already high subtype diversity in Portugal seems to be increasing due to infections with sub-subtype A1 virus. We performed phylogenetic analysis of 65 A1 sequences newly obtained from 14 Portuguese hospitals and 425 closely related database sequences. 80% of the A1 Portuguese isolates gathered in a main phylogenetic clade (MA1). Six transmission clusters were identified in MA1, encompassing isolates from Portugal, Spain, France, and United Kingdom. The most common transmission route identified was men who have sex with men. The origin of the MA1 was linked to Greece, with the first introduction to Portugal dating back to 1996 (95% HPD: 1993.6-1999.2). Individuals infected with MA1 virus revealed lower viral loads and higher CD4+ T-cell counts in comparison with those infected by subtype B. The expanding A1 clusters in Portugal are connected to other European countries and share a recent common ancestor with the Greek A1 outbreak. The recent expansion of this HIV-1 subtype might be related to a slower disease progression leading to a population level delay in its diagnostic.
  • Brain functional connectivity is altered in patients with Takotsubo Syndrome
    Publication . Silva, AR; Magalhães, R; Arantes, C; Moreira, PS; Rodrigues, M; Marques, P; Marques, J; Sousa, N; Pereira, VH
    Takotsubo syndrome (TTS) is an acute, reversible cardiomyopathy. The central autonomic nervous system (ANS) is believed to play a role in this disease. The aim of the present study was to investigate the patterns of brain functional connectivity in a sample of patients who had experienced a previous episode of TTS. Brain functional connectivity, both at rest and in response to the stressful stimulus of topical cold stimulation, was explored using functional magnetic resonance imaging (fMRI), network-based statistics (NBS) and graph theory analysis (GTA) in a population consisting of eight patients with a previous episode of TTS and eight sex- and age-matched controls. At rest, a network characterized by increased connectivity in the TTS group compared to controls and comprising elements of the central ANS was identified. GTA revealed increased local efficiency, clustering and strength in regions of the bilateral hippocampus in subjects with a previous episode of TTS. When stressed by local exposure to cold, the TTS group differed significantly from both a pre-stress baseline interval and from the control group, showing increased connectivity in a network that included the left amygdala and the right insula. Based on the results, patients with TTS display a reorganization of cortical and subcortical networks, including areas associated with the emotional response and autonomic regulation. The findings tend to support the hypothesis that a deregulation of autonomic control at the central level plays a significant role in this syndrome.
  • Palliative splenic irradiation for symptomatic splenomegaly in non-Hodgkin lymphoma
    Publication . Oliveira, LC; Fardilha, C; Louro, M; Pinheiro, C; Sousa, A; Marques, H; Costa, P
    INTRODUCTION AND AIMS: Splenic marginal zone lymphoma, an uncommon subtype of non-Hodgkin lymphoma (NHL), is usually present with symptomatic splenomegaly. Although splenectomy has long been considered the first-line therapy in symptomatic or cytopenic patients, it can lead to significant morbidity and mortality. Splenic irradiation is an option for patients who have a poor response to systemic therapy and/or are not surgical candidates. In this paper, we present a case report of a patient who received splenic radiotherapy for symptomatic splenomegaly. METHODS: An 85-year-old Caucasian man with a 4 year history of low-grade NHL presented with progressive pancytopenia, significant weight loss and symptomatic splenomegaly (abdominal discomfort, sense of fullness and limitation of mobility due to spleen size). The patient refused splenectomy and, in December 2017, was referred to palliative splenic radiotherapy. He was initially treated with five fractions of one Grey (Gy) in order to evaluate clinical and haematology response. After that, 1.5 Gy daily, 5 days a week for 3 weeks. 3D conformal radiotherapy, multiple fields and mixed energy (6 and 15 Mv) were used. RESULTS: Radiotherapy allowed significant splenic reduction to almost half the size, resolving abdominal discomfort and improving quality of life. There was no decline of haemoglobin, leukocytes and platelet counts; in fact, there was a marginal increase. CONCLUSION: Palliative splenic irradiation was well tolerated confirming that it is a safe treatment option for palliation of symptomatic splenomegaly. Thereby, splenic irradiation should be strongly considered in the management of symptomatic splenomegaly, for selected patients who are refractory to or unsuitable for other options or when the patient refuses other treatments.
  • Late presentation of vesicoureteral reflux: An unusual cause of pyelonephritis in adults
    Publication . Pereira, B; Macedo, C; Anacleto, S; Gonçalves, M; Lima, E; Carvalho-Dias, E
    INTRODUCTION: Vesicoureteral reflux (VUR) corresponds to the reflux of urine from the bladder into the upper urinary system. It can be a congenital or an acquired anomaly and although its incidence is high in children it is uncommon in the adult life. One of its presentations in the adult population is the presence of recurrent Pyelonephritis. CASE PRESENTATION: Here we report a case of an adult patient with repetitive uncomplicated pyelonephritis caused by VUR. VUR was successfully managed endoscopically with subureteral injection of a bulking agent. A literature review of adult presenting VUR was performed. DISCUSSION: The first presentation of VUR in the adult life is rare. One of the most typical presentation is the presence of recurrent uncomplicated Pyelonephritis. Although no guidelines exists to study the presence of VUR in adult patients with Pyelonephritis, in the presence of several recurrent episodes of Pyelonephritis we should think in VUR as a possible cause. Even in adults, endoscopic management of VUR is an effective treatment with low morbidity. CONCLUSION: VUR can first present in the adult life, with recurrent episodes of UTI. The diagnosis is a suspicious one and is confirmed by VUCG. VUR in adults can be effectively managed with endoscopic injection of bulking agents.
  • An uncommon diagnosis done by colonoscopy
    Publication . Costa, RS; Costa, JM; Ferreira, A; Gonçalves, R; Rolanda, C
  • WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma
    Publication . Gonçalves, CS; Vieira de Castro, J; Pojo, M; Martins, EP; Queirós, S; Chautard, E; Taipa, R; Pires, MM; Pinto, AA; Pardal, F; Custódia, C; Faria, CC; Clara, C; Reis, RM; Sousa, N; Costa, BM
    Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. Methods: WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects in vitro and in vivo. Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect. Results: We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typical oncogenic activities in GBM cells, including viability, proliferation, glioma stem cell capacity, invasion, migration, and resistance to temozolomide chemotherapy. Concordantly, in in vivo orthotopic GBM mice models, using both overexpressing and silencing models, WNT6 expression was associated with shorter overall survival, and increased features of tumor aggressiveness. Mechanistically, WNT6 contributes to activate typical oncogenic pathways, including Src and STAT, which intertwined with the WNT pathway may be critical effectors of WNT6-associated aggressiveness in GBM. Clinically, we establish WNT6 as an independent prognostic biomarker of shorter survival in GBM patients from several independent cohorts. Conclusion: Our findings establish WNT6 as a novel oncogene in GBM, opening opportunities to develop more rational therapies to treat this highly aggressive tumor.
  • Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients
    Publication . Ferreira, MB; Pereira, PAl; Parreira, M; Sousa, I; Figueiredo, J; Cerqueira, JJ; Macedo, AF
    BACKGROUND: The Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop. OBJECTIVES: The aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task. METHODS: We measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group. RESULTS: Patients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits. CONCLUSIONS: Our findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS..
  • [Smoking Cessation after Bladder Cancer Diagnosis]
    Publication . Mota, P; Sousa, PM; Botelho, F; Carvalho-Dias, E; Cordeiro, A; Torres, JP; Morais, N; Anacleto, S; Lima, E
    INTRODUCTION: Smoking is an important risk factor for the development, recurrence and progression of bladder cancer. Our aim was to analyze smoking habits after diagnosis in bladder cancer patients. Additionally, we evaluated patient knowledge about smoking as a risk factor and the urologist role in promoting abstinence. MATERIAL AND METHODS: A cross-sectional, observational and descriptive study was performed in bladder cancer patients, diagnosed between January 2013 and September 2015 (n = 160) in Braga Hospital, in Portugal. RESULTS: Smoking history was present in 71.9% of the sample, with 21.9% current smokers, (40.7% of abstinence after diagnosis). Smoking was acknowledged as a risk factor by 74.4% of the sample, with only 51.3% of ever smokers and 24.4% of non-smokers recognizing smoking as the leading risk factor (p = 0.008). The presence of other household smokers were significantly higher in patients who continued smoking (40%) than in ex-smokers after diagnosis (4.2%) (p = 0.005). The majority of smokers at diagnosis (83.1%) were advised to quit by their urologist, but only one smoker (1.7%) was offered any specific intervention to aid in cessation. DISCUSSION: Smoking is not recognized as the leading risk factor for bladder cancer. This limited awareness, associated with the known difficulties in quitting smoking and the observed lack of smoking cessation interventions, may account for the high current smoking prevalence, albeit in line with other studies. CONCLUSION: This study highlights the need for efficient smoking cessation programs directed to bladder cancer patients.
  • Generation of an integration-free induced pluripotent stem cell line (CSC-43) from a patient with sporadic Parkinson's disease
    Publication . Marote, A; Pomeshchik, Y; Goldwurm, S; Collin, A; Lamas, NJ; Pinto, L; Salgado, AJ; Roybon, L
    An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD). Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.