HCV Infection in Patients with Hereditary Bleeding Disorders

Introduction: Hepatitis C virus (HCV) infection in patients with hereditary bleeding disorders (HBDs), as a consequence of treatment with transfusion of human bloodderived components between the late 1970s and 1980s, represents a major health concern. Objectives: Assessment and evaluation of the burden of HCV infection, its complications, and treatment in a population of patients with HBDs. Methods: Analysis of a series of 161 patients with HBDs treated in the Immunohemotherapy Service of the Centro Hospitalar de Lisboa Central (Lisboa, Portugal), consultation and systematic review of the patients clinical processes, elaboration of a database comprising the information gathered; and statistical study of its variables: age, gender, degree of severity of the bleeding disorder, treatment modality, and major and minor complications of HCV infection. Results: Sixty-five (40%) of the 161 patients have HCV infection. Among the patients with hemophilia A, 36% are severe and 62% of those have HCV infection; 9% moderate with 57%; 25% mild with 20%. In the hemophilia B group, 8% are severe with 23% infected and 6% moderate or mild with 10%. Concerning the patients with von Willebrand disease, 12% have type 2 with 16% infected and 4% have type 3 with 86%. Conclusions: HCV infection represents a very significant complication of the treatment employed in the past in the studied population. Considering that most of these patients were infected in the late 1970s and early 1980s, and the natural evolution of HCV infection in patients without bleeding disorders, it is expected that the prevalence of major complications will rise significantly in the coming years. Prophylactic measures should be implemented to enhance the follow-up protocols and prevent further development of liver damage in these patients

Standardization of Power-from-Shore Grid Connections for Offshore Oil & Gas Production

Offshore oil and gas (O&G) production is typically powered by local diesel engines or gas turbines. Power-from-shore (PFS) is an alternative that takes advantage of onshore renewable production and reduces greenhouse emissions but is limited to bespoke projects that are tailored to the characteristics of each site. This lack of repetition leads to an increase in the construction risk, delivery time, and lifecycle costs, therefore limiting their large-scale deployment. Furthermore, the absence of standardized designs is also notorious in mature applications such as offshore wind farms (OWF) despite their long-standing track record, with the negative consequences extensively covered in the literature. This research paper addresses offshore transmission standardization in two parts. First, by providing the scientific community with a review of the existing offshore O&G production and substations and secondly, by outlining a lean optioneering algorithm for the cost-optimized and technically feasible selection of the key design criteria. The exercise is centred on the main limiting component of the transmission systems—the cables. As such, it addresses their operational range and the cost to calculate the most effective configuration in terms of voltage and rated power. The end goal, based on the spread of connection proposals, is to cluster the candidates to a limited set of grid connection options, the achievement of which the model has been shown to be adequate.info:eu-repo/semantics/publishedVersio

Colorectal Endoscopic Submucosal Dissection in a Western Center: Analysis of Outcomes and Safety Profile

Introduction: Endoscopic submucosal dissection (ESD) is a well-established endoscopic technique for the treatment of gastrointestinal lesions. Colorectal ESD outcomes are less reported in the Western literature, and Portuguese data are still very scarce. Our aim was to describe our experience on colorectal ESD regarding its outcomes and safety profile. Methods: We conducted a retrospective evaluation of recorded data on ESDs performed between 2015 and 2020. Only ESDs performed on epithelial neoplastic lesions were selected for further analysis. Results: Of a total of 167 colorectal ESDs, 153 were included. Technical success was achieved in 147 procedures (96%). The lesions were located in the colon (n = 24) and rectum (n = 123). The en bloc resection rate was 92% and 97%, the R0 resection rate was 83% and 82%, and the curative resection rate was 79% and 78% for the colon and the rectum, respectively. The need for a hybrid technique was the only risk factor for piecemeal or R1 resection. We report a perforation rate of 3.4% and a 4.1% rate of delayed bleeding; all the adverse events were manageable endoscopically, without the need of blood transfusions or surgery. Most of the lesions were laterally spreading tumours of the granular mixed type (70%), and 20% of the lesions were malignant (12% submucosal and 8% intramucosal cancer). Conclusion: Our series on colorectal ESD reports a very good efficacy and safety profile. This technique can be applied by endoscopists experienced in ESD

Rhipicephalus bursa Sialotranscriptomic Response to Blood Feeding and Babesia ovis Infection: Identification of Candidate Protective Antigens

Ticks are among the most prevalent blood-feeding arthropods, and they act as vectors and reservoirs for numerous pathogens. Sialotranscriptomic characterizations of tick responses to blood feeding and pathogen infections can offer new insights into the molecular interplay occurring at the tick-host-pathogen interface. In the present study, we aimed to identify and characterize Rhipicephalus bursa salivary gland (SG) genes that were differentially expressed in response to blood feeding and Babesia ovis infection. Our experimental approach consisted of RNA sequencing of SG from three different tick samples, fed-infected, fed-uninfected, and unfed-uninfected, for characterization and inter-comparison. Overall, 7,272 expressed sequence tags (ESTs) were constructed from unfed-uninfected, 13,819 ESTs from fed-uninfected, and 15,292 ESTs from fed-infected ticks. Two catalogs of transcripts that were differentially expressed in response to blood feeding and B. ovis infection were produced. Four genes coding for a putative vitellogenin-3, lachesin, a glycine rich protein, and a secreted cement protein were selected for RNA interference functional studies. A reduction of 92, 65, and 51% was observed in vitellogenin-3, secreted cement, and lachesin mRNA levels in SG, respectively. The vitellogenin-3 knockdown led to increased tick mortality, with 77% of ticks dying post-infestation. The reduction of the secreted cement protein-mRNA levels resulted in 46% of ticks being incapable of correctly attaching to the host and significantly lower female weights post-feeding in comparison to the control group. The lachesin knockdown resulted in a 70% reduction of the levels associated with B. ovis infection in R. bursa SG and 70% mortality. These results improved our understanding of the role of tick SG genes in Babesia infection/proliferation and tick feeding. Moreover, lachesin, vitellogenin-3, and secreted cement proteins were validated as candidate protective antigens for the development of novel tick and tick-borne disease control measures.FCT for funds to GHTM UID/Multi/04413/2013.info:eu-repo/semantics/publishedVersio

Recurrent Gastrointestinal Bleeding from Dieulafoy's Lesions in a Patient with Type 1 von Willebrand Disease: A Rare Association

Von Willebrand disease (vWD) is the most prevalent hereditary bleeding disorder, affecting 0.6-1.3% of the population. While gastrointestinal bleeding from angiodysplasia is a well-known complication of vWD, the same is not true for Dieulafoy's lesions (DLs). We report the case of a 21-year-old black male with type 1 vWD and 2 previous hospital admissions for severe anemia with no visible blood loss. In both episodes, DLs were identified and treated endoscopically, one in the stomach and another in the duodenum. The patient presented to the emergency department in September 2016 with dizziness, fatigue, and again no visible blood loss. He was hemodynamically stable, and laboratory workup showed a hemoglobin level of 3.4 g/dL. After transfusion of packed red blood cells, intravenous iron, and von Willebrand factor/factor VIII concentrate infusions, the patient underwent upper endoscopy and colonoscopy, which were normal. Small-bowel capsule endoscopy showed dark blood and a fresh clot in the proximal jejunum. At this site, push enteroscopy identified a pulsatile vessel with an overlying minimal mucosal defect, consistent with a DL, type 2b of the Yano-Yamamoto classification, which was successfully treated with adrenaline and 2 hemoclips. The patient remains stable after 18 months of follow-up, with a hemoglobin level of 13.2 g/dL. This is a case of recurrent severe occult gastrointestinal bleeding from multiple DL in a young patient with vWD who is otherwise healthy. Three other cases of DL bleeding in the setting of vWD have been reported in the literature, suggesting a possible association between these 2 entities.info:eu-repo/semantics/publishedVersio

Early father–child and mother–child attachment relationships: contributions to preschoolers’ social competence

The main goal of this study was to explore the contributions of early father-child and mother-child attachment relationships to children's later social competence with their preschool peers; possible unique and shared contributions were tested. Using a multi-method design and focusing on direct observation, attachment was assessed at home at age 3 with the Attachment Behavior Q-sort (AQS) and two years later social competence was assessed at classrooms of 5-year-olds using a set of seven measurement indicators that are part of the Hierarchical Model of Social Competence. Results show that attachment to each parent made unique and significant contributions to children's social competence and suggested the possibility that each caregiver may have somewhat different patterns of influence on the different indicators of children's social competence. Findings also suggest the possibility that a secure attachment with one parent may buffer the impact of having an insecure relationship with the other. Due to sample size, these results should be seen as a starting point to generate new and larger studies.info:eu-repo/semantics/publishedVersio

Relevância da Infecção VHC em Coagulopatias Congénitas

Introdução: A infecção pelo vírus da hepatite C (VHC) em doentes com coagulopatias congénitas (CC), como consequência da terapêutica empregue entre os anos 70 e 80 com transfusão de derivados de plasma humano, constitui um problema de saúde substancial e relevante. Objectivos: Análise e avaliação da relevância representada pela infecção VHC e suas complicações no tratamento duma população de doentes com CC. Métodos: Análise retrospectiva duma série de 161 doentes com CC tratados no Serviço de Imunohemoterapia do Centro Hospitalar de Lisboa Central (Lisboa, Portugal). Revisão sistemática de processos clínicos. Elaboração duma base de dados compreendendo a informação reunida e estudo estatístico das suas variáveis: idade, género, tipo e gravidade da coagulopatia e modalidade de tratamento. Relativamente à infecção por VHC: genotipo, tipo e duração do tratamento, frequência de resposta mantida ao tratamento e recidiva, co-infecções e complicações major e minor. Resultados: Dos 161 doentes 65 (40%) estão infectados pelo VHC. Dos doentes com hemofilia A: 36% são grave e 62% dos quais estão infectados pelo VHC; 9% moderada com 57%; 25% ligeira com 20%. No grupo da hemofilia B: 8% são grave com 23% infectados e 6% moderada ou ligeira com 10%. Relativamente ao grupo com doença de von Willebrand: 12% são tipo 2 com 16% infectados e 4% tipo 3 com 86%. Uma coorte de 26 doentes foi submetida a terapêutica para a infecção pelo VHC, com o primeiro doente a receber tratamento em 1993. Destes, 5 eram seropositivos para o VIH. O tratamento variou de monoterapia com interferão a terapêutica combinada de interferão ou interferão-peguilado com ribavirina. Conclusões: A infecção pelo VHC representa uma complicação significativa do tratamento empregue no passado na população em estudo. Considerando que a maioria destes doentes foi infectada nos finais dos anos 70 e início dos anos 80 assim como a evolução natural da infecção pelo VHC em doentes sem CC, prevê-se que a prevalência de complicações major deverá aumentar significativamente nos próximos anos. É de suma importância a implementação de medidas profilácticas na revisão e adaptação dos protocolos de seguimento de forma a prevenir a progressão da patologia hepática nestes doentes

Heparan sulfate glycosaminoglycans: (un)expected allies in cancer clinical management

In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients’ management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and by the grant POCI-01-0145-FEDER-028489 (to A.M.). J.P. and C.M. are funded by FCT PhD scholarships SFRH/BD/137319/2018 and 2020.06412.BD, respectively. The APC was funded by FCT grant POCI-01-0145-FEDER-028489. The authors acknowledge the support of the COST Action CA18103 INNOGLY