Comment on Bress et al. Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial. Diabetes Care 2017;40:1401-1408.

info:eu-repo/semantics/publishedVersio

O problema das identidades culturais e políticas europeias

Uma abordagem à dinâmica de entrosamento das nações europeias ao longo dos tempos, com base nos espíritos coletivistas e individualistas que as unem e desunem ao longo da história e dão origem ao problema europeu. Abordagem esta, condimentada com o pensamento de Jorge Semprún. Escritor, político, resistente anti-nazi, prisioneiro do campo de Buchenwald, espanhol de nascimento, francês de coração, germanófono, mas sobretudo, europeísta. Pensador que apresenta a sua visão da Europa numa perspectiva que, por via da sua experiência de vida, muito poucos poderiam espelhar; Abstract: An approach on the European nations' dynamics and entanglement over the ages. Based on the collectivist and individualistic spirits that unite and disunite alternately these nations throughout its history, originating Europes’ problem. This approach is further on enriched by the thought of Jorge Semprún. A writer, politician, anti-nazi resistant, Buchenwald concentration camp prisoner, spanish born, french in his heart, german speaker, but above all, europeanist. A thinker that presents his vision of Europe in a perspective that, by his own life experience, very few could mirror

Efetividade do Dispositivo Intra-Uterino de Levonorgestrel no Tratamento de Hemorragia Uterina Anómala em Mulheres Obesas

Objective:We aimed to identify if there was any difference in Levonorgestrel-releasing intrauterine system (LNG-IUS) efficacy or weight gain when used in heavy menstrual bleeding (HMB) treatment, between obese and non-obese women. Population and methods: This was a case-controlled retrospective study undertaken between 2002-2007. 194 women with HMB were treated with LNG-IUS and stratified into two groups accordingly with body mass index (BMI): Obese Group – BMI ≥ 30 (n=53) and Non-obese Group – BMI < 30 (n=141). Age, weight, days of spotting and days of menses were analyzed at 1, 3 and 6 months after insertion and then annually until 2 years. Analytic parameters of anemia (hemoglobin, serum ferritin, mean corpuscular volume) were reviewed at pre-insertion, at 6 months and then annually until 2 years. Results: During the 2-year follow-up there was a similar improvement in two groups regarding duration of menses, spotting and in analytic parameters of anemia. A statistically significant improvement was observed in obese group after 2 years of treatment regarding analytic parameters of anemia and menstrual characteristics, without weight gain. Conclusion: In obese women, the LNG-IUS is an effective treatment for heavy menstrual bleeding, without being associated to weight gain

Regional White Matter Atrophy Correlates with Spike Activity in Encephalopathy Related to Status Epilepticus During Slow Sleep (ESES) After Early Thalamic Lesions

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is an age-related, epileptic syndrome, which associates cognitive/behavioral disturbances with a peculiar pattern of spike activity. One promising line of research is the study of ESES in cases of early thalamic lesions. We studied 7 ESES patients with unilateral thalamic lesions using magnetic resonance imaging to assess regional white matter (WM) and thalamic nuclei volume differences, and long-term electroencephalogram recordings to localize the epileptogenic cortex. N170 event-related potentials were used to demonstrate the dysfunctional character of the WM abnormalities. Diffusion-weighted images in a subset of 4 patients were used to parcellate the thalamus and evaluate volume asymmetries, based on cortical connectivity. Large WM regional atrophy in the hemisphere with the thalamic lesion was associated with both cortical dysfunction and epileptic activity. A correlation was demonstrated between lesions in the pulvinar and the mediodorsal thalamic nuclei and WM atrophy of the corresponding cortical projection areas. We propose that these abnormalities are due to the widespread structural disconnection produced by the thalamic lesions associated to a yet unknown age-dependent factor. Further exploration of WM regional atrophy association with the spike activity in other etiologies could lend support to the cortical disconnection role in ESES genesis.info:eu-repo/semantics/publishedVersio

Intra-urban variation in tuberculosis and community socioeconomic deprivation in Lisbon metropolitan area: a Bayesian approach

Background: Multidrug resistant tuberculosis (MDR-TB) is a recognized threat to global efforts to TB control and remains a priority of the National Tuberculosis Programs. Additionally, social determinants and socioeconomic deprivation have since long been associated with worse health and perceived as important risk factors for TB. This study aimed to analyze the spatial distribution of non-MDR-TB and MDR-TB across parishes of the Lisbon metropolitan area of Portugal and to estimate the association between non-MDR-TB and MDR-TB and socioeconomic deprivation. Methods: In this study, we used hierarchical Bayesian spatial models to analyze the spatial distribution of notification of non-MDR-TB and MDR-TB cases for the period from 2000 to 2016 across 127 parishes of the seven municipalities of the Lisbon metropolitan area (Almada, Amadora, Lisboa, Loures, Odivelas, Oeiras, Sintra), using the Portuguese TB Surveillance System (SVIG-TB). In order to characterise the populations, we used the European Deprivation Index for Portugal (EDI-PT) as an indicator of poverty and estimated the association between non-MDR-TB and MDR-TB and socioeconomic deprivation. Results: The notification rates per 10,000 population of non-MDR TB ranged from 18.95 to 217.49 notifications and that of MDR TB ranged from 0.83 to 3.70. We identified 54 high-risk areas for non-MDR-TB and 13 high-risk areas for MDR-TB. Parishes in the third [relative risk (RR) = 1.281, 95% credible interval (CrI): 1.021–1.606], fourth (RR = 1.786, 95% CrI: 1.420–2.241) and fifth (RR = 1.935, 95% CrI: 1.536–2.438) quintile of socioeconomic deprivation presented higher non-MDR-TB notifications rates. Parishes in the fourth (RR = 2.246, 95% CrI: 1.374–3.684) and fifth (RR = 1.828, 95% CrI: 1.049–3.155) quintile of socioeconomic deprivation also presented higher MDR-TB notifications rates. Conclusions: We demonstrated significant heterogeneity in the spatial distribution of both non-MDR-TB and MDR-TB at the parish level and we found that socioeconomically disadvantaged parishes are disproportionally affected by both non-MDR-TB and MDR-TB. Our findings suggest that the emergence of MDR-TB and transmission are specific from each location and often different from the non-MDR-TB settings. We identified priority areas for intervention for a more efficient plan of control and prevention of non-MDR-TB and MDR-TB. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s).This work has been funded by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020, UIDP/50026/2020 and PTDC/SAU-PUB/29521/2017. This study was also supported by FEDER through the Operational Programme Competitiveness and Internationalization and national funding through the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020). Ana Isabel Ribeiro was supported by National Funds through FCT, under the programme of ‘Stimulus of Scientific Employment—Individual Support’ within the contract CEECIND/02386/2018

Immunology and mammary cancer development: addressing the role of mast cells

Background: Mammary cancer is one of the most frequent cancers worldwide. Mast cells are among the cells of tumor microenvironment and have been associated with increased angiogenesis and poor prognosis. Despite this, the role of mast cells on mammary cancer is not fully elucidated. In this way, this work studied the role of mast cells in a rat model of mammary cancer chemically-induced. Materials and Methods: All experiments were performed in accordance with the Portuguese and European legislation on the protection of animals used for scientific purposes. The experiments were approved by the Portuguese (no.008961) and University (CE_12-2013) Ethics Committees. Thirty- four female Sprague-Dawley rats were randomly divided into five experimental groups. At seven weeks of age, mammary tumors’ development was induced in animals from groups I, II, III (n = 10+10+10) by a single intraperitoneal injection of the carcinogen N-methyl-N-nitrosourea (MNU). Groups II and IV (n = 2) were treated with ketotifen in drinking water (1 mg/kg/day, 7 days/week) immediately after the MNU ad- ministration for 18 weeks, while the group III received the ketotifen after the development of the first mammary tumor. Groups I and V (n = 2) received only water. Animals were sacrificed at 25 weeks of age by an overdose of ketamine and xylazine, followed by an exsanguination by cardiac puncture. Mammary tumors were collected and immersed in formalin for posterior analysis. Tumors’ vascularization, proliferation and apoptosis were also assessed by immunohistochemistry (Vascular Endothelial Growth Factor (VEGF)-A, Ki-67, and caspase-3 and caspase-9). Results: Animals from groups IV and V did not develop any mammary tumor. Twenty-one animals (six animals from group I, eight animals from group II and seven animals from group III) developed a total of 58 mammary tumors, mainly classified as papillary non-invasive carcinomas. Tumors’ vascularization was similar among groups (P > 0.05). Mammary tumors from group II exhibited the lowest prolif- eration (P < 0.05) and apoptotic indexes. Conclusions: The mainly positive effect of the ketotifen administration seems to be the reduction of tumor prolifera- tion when the drug was administered before mammary tumor development

New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters.

The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such as Mycobacterium bovis BCG or M. smegmatis was made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5 promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinant M. smegmatis bacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in both M. smegmatis and M. bovisBCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of the Schistosoma mansoni antigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response

Neurological Manifestations in Primary Immunodeficiencies

As imunodeficiências primárias são um grupo heterogéneo de doenças individualmente raras. A sua associação a manifestações neurológicas não é rara, sendo os mecanismos fisiopatológicos implicados distintos consoante a patologia em causa. As manifestações neurológicas podem ser a característica predominante da doença ou estar presentes de forma ligeira e/ou inconstante. O correto reconhecimento desta associação pode permitir um diagnóstico atempado destas doenças e o desenvolvimento de estratégias preventivas e terapêuticas. Os autores fazem uma revisão e sistematização das imunodeficiências primárias em que se verifica esta relação, sumariando as manifestações neurológicas e imunes de cada uma das patologias.info:eu-repo/semantics/publishedVersio

Downbeat Nystagmus in Episodic Ataxia Type 1 Associated with a Novel KCNA1 Mutation

info:eu-repo/semantics/publishedVersio

The influence of physical exercise on oestrogen and androgen receptor expression in a chemically and hormonally-induced rat model of prostate cancer

Background: Oestrogen (ER) and androgen (AR) recep- tors play an important role in normal prostate development and are also implied in prostate cancer (PCa) development. Several studies suggested that physical activity may decrease the risk of PCa development and also changes sexual hor- mones and their receptors. This study aimed to evaluate the effects of physical exercise on ERα and AR expression in a rat model of chemically and hormonally-induced PCa. Materials and Methods: Fifty-five male Wistar Unilever rats of 12 weeks of age were randomly divided into four groups: control sedentary (n = 10), control exercised (n = 10), induced sedentary (n = 15) and induced exercised (n = 20). Animals from exercised groups started the exercise training in a treadmill (Treadmill Control LE 8710, Harvard Apparatus, USA), at the age of 8 weeks, for 35 weeks (5 days/week). The protocol for PCa induction started at 12 weeks of age and consisted of sequential administration of flutamide (50 mg/kg, TCI Chemicals), testosterone propion- ate (100 mg/kg, TCI Chemicals) and N-methyl-N-nitrosourea (30 mg/kg, Isopac®, Sigma Chemical Co.), followed by sub- cutaneous implants of crystalline testosterone. Animals were sacrificed at 61 weeks of age and a complete necropsy was performed. All experiments were approved by DGAV (no. 021326). Antibodies for Erα (1:500, clone 6F11, Novocastra) and AR (clone PG21, Merck Millipore) were used for the immunohistochemical study. The staining extension was evaluated in normal prostate tissue and in dorsolateral pros- tate lesions (hyperplasia, dysplasia, prostatic intraepithelial neoplasia (PIN) and microinvasive carcinoma) and assessed to five levels (0%, 75%), con- sidering the extension of immunopositive tissue. Data was analysed with SPSS 25.Results: The normal prostate tissue and dorsolateral prostate lesions of animals from all groups were immunopositive for Erα and AR. However, the groups showed high immunoposi- tivity for AR and low positivity for Erα ( 0.05). The malignant lesions (PIN and microinvasive carcinoma) showed lower AR expression when compared with normal prostate tissue in all groups. Conclusions: As expected, the AR expression was lower in malignant lesions. Inversely to that reported in other studies, the exercise training did not modify the ERα and AR expres- sion, which may be related to the duration and type of exer- cise performed