Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases

HNF1B mutations are associated with a Gitelman-like tubulopathy that develops during childhood

Mutations in the transcription factor hepatocyte nuclear factor 1B (HNF1B) are the most common inherited cause of renal malformations, yet also associated with renal tubular dysfunction, most prominently magnesium wasting with hypomagnesemia. The presence of hypomagnesemia has been proposed to help select appropriate patients for genetic testing. Yet, in a large cohort, hypomagnesemia was discriminatory only in adult, but not in pediatric patients. We therefore investigated whether hypomagnesemia and other biochemical changes develop with age.This article is freely available via Open Access. Click on the Additional Link to access full-text

Avaliação da vulnerabilidade sísmica do núcleo urbano antigo do Seixal

A avaliação do risco sísmico, tal como de outros fenómenos naturais, tem vindo a ganhar protagonismo ao longo das últimas décadas, sendo considerado primordial na definição de estratégias de planeamento e gestão urbana. A avaliação da vulnerabilidade sísmica de edifícios existentes, na perspectiva da mitigação do risco sísmico, deve colocar-se não só em relação aos edifícado monumental ou culturalmente valiosos, mas também em relação a aglomerados de edifícios em núcleos urbanos, particularmente nos núcleos urbanos antigos. A análise do desempenho de edifícios em sismos recentes tem permitido identificar quais os aspectos estruturais que mais influenciam a sua vulnerabilidade e o desenvolvimento de mecanismos de danos. Neste artigo analisam-se os resultados da avaliação da vulnerabilidade sísmica do núcleo urbano antigo do Seixal, obtidos através da aplicação de uma metodologia baseada num índice de vulnerabilidade. Através da avaliação da vulnerabilidade sísmica, esta metodologia permite ainda estimar dano e criar cenários de perda. Estes resultados serão apresentados tirando partido de uma ferramenta integrada num Sistema de Informação Geográfica (SIG)

It’s normal unless it turns into physical aggression: a study of Portuguese Journalists’ perceptions of (gendered) online harassment

In January 2021, while the country’s daily Covid-19 numbers were hitting record highs, Portugal headed to the polls to elect its future head of state. The campaign was marked by the actions and words of a new far-right party (Chega), which held a campaign characterised by violent incidents with journalists. Later in the year, local elections provided new opportunities for these political actors to confront journalists and make female journalists their preferential targets. The attacks were not just face-to-face but also on social media, in reiterated hate speech messages and direct threats, particularly against female journalists (CCPJ 2021). What made these events significant is that hate speech and online harassment became more visible for both the public and journalists themselves. Having a presence online is expected if not required from journalists today. While digital networking helps establish connections and reach a wider community, it also exposes media professionals to abuse. The dangers of hate speech in journalism are well known and hate speech presents a major challenge to today's journalists (Holton, 2021), as it became their “new normal” (Waisbord, 2020). Women in particular are preferential targets of trolls (Nadim e Fladmoe, 2019; Edström, 2016; UNESCO, 2021; Chen et al, 2020; Adams, 2018). Under different names, such as cyber gender harassment (Citron, 2011) or gendertrolling (Mantilla, 2013), the consequences of gender-based online hate speech hate are not only to female journalists’ mental health and psychological wellbeing but also on public life, as it may have a “chilling effect” in limiting the types of stories and topics that are covered (Townend, 2017; UNESCO, 2021). With few exceptions (Simões, 2021; Silva, 2021), little is known about online violence against Portuguese journalists. This research examines how online abuse is experienced and tackled by Portuguese journalists by measuring self-reported incidents, effects, and trust in existing safety mechanisms. Further, we specifically address the prevalence of online harassment and violence against women journalists and their perceptions of the issue. Theoretically, the article bridges the research on online harassment, mob censorship and gender in journalism. Empirically, it draws on a nationwide survey of journalists and, to explore in more detail the meanings of its quantitative data and the gender aspects of experience. Findings are combined with data from semi-structured interviews conducted with women journalists from diverse media and fields. Professionals feel an increasing hostility aggravated by the digital environment. Half of the surveyed journalists have experienced online violence to some degree, including sexual harassment. Journalists further evidenced low levels of trust in protection mechanisms or a lack of awareness of them. Findings also suggest feelings of resignation towards online abuse, seen as intrinsic to the job, demonstrating a sense of understatement of the attacks. The paper argues that these sentiments contribute to a normalisation of online violence and highlights the need to discuss online abuse within the profession.N/

Histone Methylation by NUE, a Novel Nuclear Effector of the Intracellular Pathogen Chlamydia trachomatis

Sequence analysis of the genome of the strict intracellular pathogen Chlamydia trachomatis revealed the presence of a SET domain containing protein, proteins that primarily function as histone methyltransferases. In these studies, we demonstrated secretion of this protein via a type III secretion mechanism. During infection, the protein is translocated to the host cell nucleus and associates with chromatin. We therefore named the protein nuclear effector (NUE). Expression of NUE in mammalian cells by transfection reconstituted nuclear targeting and chromatin association. In vitro methylation assays confirmed NUE is a histone methyltransferase that targets histones H2B, H3 and H4 and itself (automethylation). Mutants deficient in automethylation demonstrated diminished activity towards histones suggesting automethylation functions to enhance enzymatic activity. Thus, NUE is secreted by Chlamydia, translocates to the host cell nucleus and has enzymatic activity towards eukaryotic substrates. This work is the first description of a bacterial effector that directly targets mammalian histones

Characterization and intracellular localization of putative Chlamydia pneumoniae effector proteins

We here describe four proteins of Chlamydia pneumoniae, which might play a role in host-pathogen interaction. The hypothetical bacterial proteins CPn0708 and CPn0712 were detected in Chlamydia pneumoniae-infected host cells by indirect immunofluorescence tests with polyclonal antisera raised against the respective proteins. While CPn0708 was localized within the inclusion body, CPn0712 was identified in the inclusion membrane and in the surrounding host cell cytosol. CPn0712 colocalizes with actin, indicating its possible interaction with components of the cytoskeleton. Investigations on CPn0809 and CPn1020, two Chlamydia pneumoniae proteins previously described to be secreted into the host cell cytosol, revealed colocalization with calnexin, a marker for the ER. Neither CPn0712, CPn0809 nor CPn1020 were able to inhibit host cell apoptosis. Furthermore, transient expression of CPn0712, CPn0809 and CPn1020 by the host cell itself had no effect on subsequent infection with Chlamydia pneumoniae. However, microarray analysis of CPn0712-expressing host cells revealed six host cell genes which were regulated as in host cells infected with Chlamydia pneumoniae, indicating the principal usefulness of heterologous expression to study the effect of Chlamydia pneumoniae proteins on host cell modulation

Use of colonoscopy as a primary screening test for colorectal cancer in average risk people

The use of colonoscopy as a primary screening test for colorectal cancer (CRC) in average risk adults is a subject of controversy. Our primary objective was to build a predictive model based on a few simple variables that could be used as a guide for identifying average risk adults more suitable for examination with colonoscopy as a primary screening test. METHODS: The prevalence of advanced adenomas was assessed by primary screening colonoscopy in 2210 consecutive adults at least 40 yr old, without known risk factors for CRC. Age, gender, and clinical and biochemical data were compared among people without adenomas, those with non-advanced adenomas, and those with any advanced neoplasm. A combined score to assess the risk of advanced adenomas was built with the variables selected by multiple logistic regression analysis. RESULTS: Neoplastic lesions were found in 617 subjects (27.9%), including 259 with at least one neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia, and 11 with invasive cancers. Advanced lesions were more frequent among men, older people, and those with a higher body mass index (BMI). These three variables were independent predictors of advanced adenomas in multivariate analysis. A score combining age, sex, and BMI was developed as a guide for identifying individuals more suitable for screening colonoscopy. CONCLUSIONS: Age, gender, and BMI can be used to build a simple score to select those average risk adults who might be candidates for primary screening colonoscop

Gastroduodenal injury after radioembolization of hepatic tumors

Radioembolization is a new tool for the treatment of hepatic tumors that consists in the injection of biocompatible microspheres carrying radioisotopes into the hepatic artery or its branches. METHODS: We have performed radioembolization in 78 patients with hepatic tumors using resin-based microspheres loaded with yttrium-90. All patients were previously evaluated to minimize the risk of hazardous irradiation to nontarget organs and to obtain the data needed for dose calculation. RESULTS: We report a complication found in three cases (3.8%) that consists of abdominal pain resulting from gastroduodenal lesions and that had a chronic, insidious course. Microscopically, microspheres were detected in the specimens obtained from all affected gastric areas. Since these gastroduodenal lesions do not appear when nonradiating microspheres are injected in animals, lesions are likely to be due to radiation and not to an ischemic effect of vascular occlusion by spheres. CONCLUSIONS: We believe that a pretreatment evaluation that includes a more thorough scrutiny of the hepatic vascularization in search of small collaterals connecting to the gastroduodenal tract can help prevent this awkward complicatio

Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy

For colorectal cancer screening, the predictive value of distal findings in the ascertainment of proximal lesions is not fully established. The aims of this study were to assess distal findings as predictors of advanced proximal neoplasia and to compare the predictive value of endoscopy alone vs. combined endoscopic and histopathologic data. METHODS: Primary colonoscopy screening was performed in 2210 consecutive, average-risk adults. Age, gender, endoscopic (size, number of polyps), and histopathologic distal findings were used as potential predictors of advanced proximal neoplasms (i.e., any adenoma > or =1 cm in size, and/or with villous histology, and/or with severe dysplasia or invasive cancer). Polyps were defined as distal if located in the descending colon, the sigmoid colon, or the rectum. Those in other locations were designated proximal. RESULTS: Neoplastic lesions, including 11 invasive cancers, were found in 617 (27.9%) patients. Advanced proximal neoplasms without any distal adenoma were present in 1.3% of patients. Of the advanced proximal lesions, 39% were not associated with any distal polyp. Older age, male gender, and distal adenoma were independent predictors of advanced proximal neoplasms. The predictive ability of a model with endoscopic data alone did not improve after inclusion of histopathologic data. In multivariate logistic regression analysis, the predictive ability of models that use age, gender, and any combination of distal findings was relatively low. The proportion of advanced proximal neoplasms identified if any distal polyp was an indication for colonoscopy was only 62%. CONCLUSIONS: A strategy in which colonoscopy is performed solely in patients with distal colonic findings is not effective screening for the detection of advanced proximal neoplasms in an average-risk populatio