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Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide. [ABSTRACT FROM AUTHOR]

Background Coccydynia has many causes, including fracture, subluxation, and hypermobility of sacrococcygeal segments. Existing treatments are limited in their effectiveness. Coccygeoplasty (CP) is a relatively new, minimally invasive treatment that appears to address this difficult clinical challenge. Objective To describe clinical results at the time of the procedure and at 3- and 12-months' follow-up of patients with coccydynia related to subluxation and coccyx hypermobility treated with the CP technique. Additionally, to determine if there is any correlation between the final imaging and clinical results at 3- and 12-months' follow-up. Methods A prospectively maintained database was used, and all patients who underwent CP for chronic coccydynia between January 2005 and October 2018 were retrospectively reviewed. All the patients had painful hypermobility (greater than 25°) with anterior flexion confirmed on radiological imaging. Alternative causes of coccydynia were excluded using CT and MRI. Procedures were performed under local anesthesia with combined fluoroscopic and CT guidance. Clinical followup was performed at two time points: 3 and 12 months after treatment using the Visual Analogue Scale (VAS). Results Twelve patients were treated in a single center. No procedural complications occurred. At 3- and 12-months' follow-up, the majority (75%) of patients had significantly lower VAS scores than at baseline, with mean changes of 3.5 and 4.9, respectively. There was no pain recurrence at 12 months and just one patient had no improvement of the pain. Follow- up CT images confirmed fixation of the sacrococcygeal bone segments in nine patients; however, no correlation was found between final imaging results and clinical outcome (p=0.1). Conclusions Patients with refractory painful coccyx subluxation and hypermobility undergoing CP have a favorable clinical response at 3- and 12-months' followup. Further studies are required to validate this technique and to identify predictors of treatment response. Coccygeoplasty may be considered a reasonable alternative to coccygectomy. [ABSTRACT FROM AUTHOR]

A glória de fazer cinema em Portugal (Manuel Mozos, 2015) and Redemption (Miguel Gomes, 2013) are recent examples of "appropriation films," a filmmaking practice that has seen important development in Portugal over the past fifteen years. The two films stand out, however, because they use fabricated archival footage (Mozos) and real archival footage (Gomes) to tell a fictional story. This places them within the scope of the "fake documentary" genre. If one accepts current scholarly definitions of appropriation films, it is possible to see these two "fake" films as apt illustrations of the epistemological and pedagogical potential of the appropriation film with respect not only to cinema but also to historical knowledge. [ABSTRACT FROM AUTHOR]

Keywords: Secondary; Trigeminal neuralgia; Pontine; Infarction EN Secondary Trigeminal neuralgia Pontine Infarction 391 392 2 08/20/21 20210901 NES 210901 Secondary trigeminal neuralgia (TN) is mainly associated with neoplasms and demyelinating diseases. TN due to pontine infarction is a rare entity and often overlooked with only few cases reported, but should be considered in the differential diagnosis of secondary TN [[2]]. [Extracted from the article]

Background Multidrug resistance 1 (MDR1) gene encodes for an ATP binding cassette transporter - Pglycoprotein (P-gp) - involved in chemoresistance to taxanes. MDR1 promoter methylation is frequent in prostate carcinoma (PCa), suggesting an epigenetic regulation but no functional correlation has been established. We aimed to elucidate the epigenetic mechanisms involved in MDR1 deregulation in PCa. Results MDR1 promoter methylation and P-gp expression were assessed in 121 PCa, 39 high-grade prostatic intraepithelial neoplasia (HGPIN), 28 benign prostatic hyperplasia (BPH) and 10 morphologically normal prostate tissue (NPT) samples, using quantitative methylation specific PCR and immunohistochemistry, respectively. PCa cell lines were exposed to a DNA methyltransferases inhibitor 5-aza-2'deoxycytidine (DAC) and histone deacetylases inhibitor trichostatin A (TSA). Methylation and histone posttranscriptional modifications status were characterized and correlated with mRNA and protein expression. MDR1 promoter methylation levels and frequency significantly increased from NPTs, to HGPIN and to PCa. Conversely, decreased or absent P-gp immunoexpression was observed in HGPIN and PCa, inversely correlating with methylation levels. Exposure to DAC alone did not alter significantly methylation levels, although increased expression was apparent. However, P-gp mRNA and protein re-expression were higher in cell lines exposed to TSA alone or combined with DAC. Accordingly, histone active marks H3Ac, H3K4me2, H3K4me3, H3K9Ac, and H4Ac were increased at the MDR1 promoter after exposure to TSA alone or combined with DAC. Conclusion Our data suggests that, in prostate carcinogenesis, MDR1 downregulation is mainly due to histone post-translational modifications. This occurs concomitantly with aberrant promoter methylation, substantiating the association with P-gp decreased expression. CpG island hypermethylation, epigenetic regulation, histone post-translational activation/repression marks, MDR1, P-gp, prostate. [ABSTRACT FROM AUTHOR]

Copyright of Ler Historia is the property of Ler Historia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses Cinematica Portuguesa-Museu do Cinema's identification and restoration of the surgical films of surgeon Eugène-Louis Doyen. Apart from a few copies held by French film archives, most of his film collection was believed to be lost. Doyen used films as a way to legitimate his new surgical techniques among the international medical community. The material history of Doyen's film collection, from the shooting of the films to their disappearance, as well as the history of all the different exhibition and distribution strategies Doyen employed, has been reconstructed in several articles.

Copyright of Ler Historia is the property of Ler Historia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The SAGA (Spt-Ada-Gcn5 acetyltransferase) coactivator complex contains distinct chromatin-modifying activities and is recruited by DNA-bound activators to regulate the expression of a subset of genes. Surprisingly, recent studies revealed little overlap between genome-wide SAGA-binding profiles and changes in gene expression upon depletion of subunits of the complex. As indicators of SAGA recruitment on chromatin, we monitored in yeast and human cells the genome-wide distribution of histone H3K9 acetylation and H2B ubiquitination, which are respectively deposited or removed by SAGA. Changes in these modifications after inactivation of the corresponding enzyme revealed that SAGA acetylates the promoters and deubiquitinates the transcribed region of all expressed genes. In agreement with this broad distribution, we show that SAGA plays a critical role for RNA polymerase II recruitment at all expressed genes. In addition, through quantification of newly synthesized RNA, we demonstrated that SAGA inactivation induced a strong decrease of mRNA synthesis at all tested genes. Analysis of the SAGA deubiquitination activity further revealed that SAGA acts on the whole transcribed genome in a very fast manner, indicating a highly dynamic association of the complex with chromatin. Thus, our study uncovers a new function for SAGA as a bone fide cofactor for all RNA polymerase II transcription. [ABSTRACT FROM AUTHOR]

Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts., Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture., Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity., Discussion: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions., Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.

Global defects in RNA polymerase II transcription might be overlooked by transcriptomic studies analyzing steady-state RNA. Indeed, the global decrease in mRNA synthesis has been shown to be compensated by a simultaneous decrease in mRNA degradation to restore normal steady-state levels. Hence, the genome-wide quantification of mRNA synthesis, independently from mRNA decay, is the best direct reflection of RNA polymerase II transcriptional activity. Here, we discuss a method using non-perturbing metabolic labeling of nascent RNAs in Saccharomyces cerevisiae (S. cerevisiae). Specifically, the cells are cultured for 6 min with a uracil analog, 4-thiouracil, and the labeled newly transcribed RNAs are purified and quantified to determine the synthesis rates of all individual mRNA. Moreover, using labeled Schizosaccharomyces pombe cells as internal standard allows comparing mRNA synthesis in different S. cerevisiae strains. Using this protocol and fitting the data with a dynamic kinetic model, the corresponding mRNA decay rates can be determined.

Regulation of gene expression includes the replacement of canonical histones for non-allelic histone variants, as well as their multiple targeting by postranslational modifications. H2A variants are highly conserved between species suggesting they execute important functions that cannot be accomplished by canonical histones. Altered expression of many H2A variants is associated to cancer. MacroH2A variants are enriched in heterocromatic foci and necessary for chromatin condensation. MacroH2A1.1 and macroH2A1.2 are two mutually exclusive isoforms. MacroH2A1.1 and macroH2A2 inhibit proliferation and are associated with better cancer prognosis; while macroH2A1.2 is associated to cancer progression. H2AX variant functions as a sensor of DNA damage and defines the cellular response towards DNA repair or apoptosis; therefore, screening approaches and therapeutic options targeting H2AX have been proposed. H2A.Z is enriched in euchromatin, acting as a proto-oncogene with established roles in hormone responsive cancers and overexpressed in endocrine-resistant disease. Other H2A family members have also been found altered in cancer, but their function remains unknown. Substantial progress has been made to understand histone H2A variants, their contribution to normal cellular function and to cancer development and progression. Yet, implementation of high resolution mass spectrometry is needed to further our knowledge on highly homologous H2A variants expression and function.

Background: Current therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in PCa cell lines., Methods: The anti-tumoral impact of RG108 in LNCaP, 22Rv1, DU145 and PC-3 cell lines was assessed through standard cell viability, apoptosis and cell cycle assays. Likewise, DNMT activity, DNMT1 expression and global levels of DNA methylation were evaluated in the same cell lines. The effectiveness of DNA demethylation was further assessed through the determination of promoter methylation and transcript levels of GSTP1, APC and RAR-β2, by quantitative methylation-specific PCR and RT-PCR, respectively., Results: RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA reexpression was only attained for GSTP1 and APC., Conclusions: RG108 is an effective tumor growth suppressor in most PCa cell lines tested. This effect is likely mediated by reversion of aberrant DNA methylation affecting cancer related-genes epigenetically silenced in PCa. However, additional mechanism might underlie the anti-tumor effects of RG108. In vivo studies are now mandatory to confirm these promising results and evaluate the potential of this compound for PCa therapy.

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes' upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2'-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients.

Thromboembolic phenomena are the most commonly reported complications during endovascular treatment of intracranial aneurysms with coils. Frequency of this complication varies in the literature, but authors reported rates ranging from 2.5 to 28%. Several mechanisms may be involved in the formation and migration of thrombus: it may be already existing inside the aneurysm and be dislocated and then migrate distally; it can be formed on the surface of the coils or catheters used, or it can appear in the remnant aneurysm sac it. Studies have shown a higher incidence of thromboembolic complications in wide neck aneurysms. In this paper we discuss the importance of prevention of thromboembolic complications during and after endovascular treatment of ruptured intracranial aneurysms. We also refer options and strategies to adopt in the event of a vascular occlusion is detected during the procedure, as the administration of inhibitors of glycoprotein IIb/IIIa or the release of an intra-cranial stent. Illustrative cases are shown. The prevention of thromboembolic complications and rapid action after the vascular occlusion is essential in order to improve the prognosis of patients undergoing endovascular treatment of ruptured intracranial aneurysms. Extensive knowledge of available options is essential to the pursuit of that goal.

Endoluminal reconstruction with flow diverter devices represents an innovative technique in the treatment of intracranial aneurysms.These new stents, self-expandable and of low porosity, are released through the microcatherization of the parent artery. The main goal of these systems is thereby rebuilding the vessel wall and excluding the aneurysmal formation of the arterial circulation.We show the preliminary results in treating 10 patients at Hospital de São José, Lisbon. These patients, with wide-necked (> 4 mm)or unfavorable dome/neck ratios (> 1.5) aneurysms, were treated with the PIPELINE® system, and angiographic control were made at three and six months. New control will be done at 12 months. The mean age of enrolled patients is 54.3 years; eight patients were female and two male. Aneurysms were incidentally discovered in two patients. The remaining patients were diagnosed during imaging investigation for headache (n = 3), visual field defect (n = 1), vertigo(n = 1) and at least one cranial palsy (n = 2). Only two patients had had prior subarachnoid hemorrhage and two patients underwent prior endovascular treatment with coils. The locations of aneurysms treated were the proximal segment of the middle cerebral artery(n = 1) and the paraophthalmic (n = 6), ophthalmic (n = 2) and cavernous (n = 4) internal carotid artery segments. Thirteen intracranial aneurysms were treated as three patients had multiple aneurysms. Control studies were conducted and shown an average degree of occlusion at three months of 74% and at six months of 86%. There was no reduction in size of one paraophthalmic artery aneurysm.The experience of this department is favorable to the use of flow-diverter devices to treat selected aneurysms. High occlusion rates were obtained given the existing challenges in the treatment of such aneurysms.