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Glioblastoma (GB) is one of the most lethal types of neoplasms. Its biologically aggressive nature and the presence of the blood-brain barrier (BBB) limit the efficacy of standard therapies. Several strategies are currently being developed to both overcome the BBB and deliver drugs site-specifically to tumor cells. This work hypothesizes a two‑pronged approach to tackle glioblastoma: drug repurposing with celecoxib and a nanoformulation using ultra-small nanostructured lipid carriers (usNLCs). Celecoxib antitumor druggable activity was inspected bioinformatically and screened in four glioma cell lines aiming at the comparison with temozolomide, as standard of care. Delving into formulation design, it was tailored aiming at (i) improving the drug solubility/loading properties, (ii) assigning a thermal-triggerable drug release based on a lipid matrix with a low melting point, and (iii) enhancing the cytotoxic effect by selecting a template targetable to tumor cells. For this purpose, an integrated analysis of the critical material attributes (CMAs), critical process parameters (CPPs) and critical quality attributes (CQAs) was conducted under the umbrella of a Quality by Design approach. CMAs that demonstrate a high-risk level for the final quality and performance of the usNLCs include the drug solubility in lipids (solid and liquid), the lipid composition (envisioning a thermoresponsive approach), the ratio between lipids (solid vs. liquid), and the surfactant type and concentration. Particle size was shown to be governed by the interaction lipid-surfactant followed by surfactant type. The drug encapsulation did not influence colloidal characteristics, making it a promising carrier for lipophilic drugs. In general,usNLCs exhibited a controlled drug release during the 72 hours at 37 ºC with a final release of ca. 25 %, while at 45 ºC this was doubled. The in vitro cellular performance depended on the surfactant type and lipid composition, with the formulations containing a sole solid lipid (Suppocire® NB) and Kolliphor® RH40 as surfactant being the most cytotoxic. usNLCs with an average diameter of ca. 70 nm and a narrow size distribution (PdI lower than 0.2) were yielded, exhibiting, high stability, drug protection, sustained and thermo‑sensitive release properties, and high cytotoxicity to glioma cells, meeting the suitable CQAs for parenteral administration. This formulation may pave the way to a multi-addressable purpose to improve address GB treatment.

ObjectiveTo investigate the perceptions of young people and adults, smokers and non-smokers about the current set of innovations introduced in 2018 into the Brazilian tobacco products’ health warnings.MethodsTwenty focus groups were conducted in five state capitals in Brazil. The participants (n=163) were segmented by smoking status, age (15–17 years, 18–55 years) and social grade (C, D–E classes) to examine cigarette packaging and explore the participants’ perceptions of health warnings.ResultsHealth warnings capture attention, eliciting apprehension, fear, disgust and concern about the negative consequences of cigarette consumption. The 2018 Brazil health warnings are spontaneously recalled by participants, even without the presence of cigarette packages. However, the analysis also reveals the challenges of overcoming communication barriers and distorted interpretations, especially among smokers. The inclusion of direct and provocative stimuli, such as the use of the word ‘you’, attracts attention and creates more proximity to the recipient of the message. The results also highlight the interest and fear elicited by warnings on toxic constituents and the importance of using contrasting colours in warnings, which differentiate them from the colours of cigarette packs.ConclusionIntroducing innovative components in health warnings can catch consumers’ attention but considering that the interviewees encountered difficulties interpreting textual warnings about toxic constituents in cigarettes, the study reinforces the importance of adopting direct language and pictures, instead of text, which can visually transmit the warning messages and the use of specific wording that generates proximity between the emitter and receiver.

Background and Aims: Colorectal cancer (CRC) is a heterogeneous disease with distinctive genetic pathways, such as chromosomal instability, microsatellite instability and methylator pathway. Our aim was to correlate clinical and genetic characteristics of CRC patients in order to understand clinical implications of tumour genotype. Methods: Single-institution retrospective cohort of patients who underwent curative surgery for CRC, from 2012 to 2014. RAS and BRAF mutations were evaluated with the real-time PCR technique Idylla®. Mismatch repair deficiency (dMMR) was characterized by absence of MLH1, MSH6, MSH2 and/or PMS2 expression, evaluated by tissue microarrays. Overall survival (OS) and disease-free survival (DFS) were assessed using survival analysis. Results: Overall, 242 patients were included (males 57.4%, age 69.3 ± 12.9 years; median follow-up 49 months). RAS-mutated tumours were associated with reduced DFS (p = 0.02) and OS (p = 0.045) in stage I–III CRC. BRAF-mutated tumours were more predominant in females and in the right colon, similarly to dMMR tumours. BRAF status did not influence OS (4 years)/DFS (3.5 years) in stage I–III disease. However, after relapse, length of survival was 3.5 months in BRAF-mutated tumours in contrast to 18.6 months in BRAF wild-type tumours (p = NS). No germline mutations in mismatch repair genes were so far identified in the patients with dMMR tumours. Molecular phenotype (RAS, BRAF and MMR) did not influence OS in metastatic patients. Our small sample size may be a limitation of the study. Conclusion: In our cohort, RAS-mutated tumours were associated with worse DFS and OS in early-stage CRC, whereas the remaining molecular variables had no prognostic influence.

Background: The rate of diabetic ketoacidosis in new-onset type 1 diabetes mellitus depends on multiple factors and is very heterogeneous between countries. An inverse relationship between the incidences of T1D and DKA seems to exist. Moreover, DKA is reported to be more common in children under 5 years old. Current data on Portuguese pediatric DKA incidence in new-onset T1D is limited. We aimed to determine the rate of DKA incidence in this population, as well as risk and protective factors.Methods: Review of data from children aged 18 years or younger with new onset T1D, referred to a pediatric endocrinology unit between January 1st, 2013 and December 31th, 2020 (8 years).Results: 276 patients were included with a median age of 9.6 years-old (0.5-17.9 years): 15,6% aged between 2 and 5 years-old and 3,6% under two years. A mean incidence of 34,5 new cases per year was observed, with an upward trend. One hundred and five (38%) presented with DKA, which was considered severe in 9,4%; 50 patients (18,1%) presented only with hyperglycemia. Non-DKA at presentation was associated with family history of T1D (p=0.016). DKA at presentation was more frequent in the age group under 2 years old (p=0.005).Conclusions: DKA’s frequency at new onset T1D is still high, although only a small proportion of cases was considered severe. A family history of T1D correlated with a non-DKA presentation, while an age under 2 years presented as a risk factor for DKA.

This chapter examines the engagement of social work academics in the policy process in Portugal. It begins by presenting an overview of social policy and the historical development of the Portuguese welfare state and by discussing the emergence of the social work profession in that country. The development of social work education in Portugal and its contemporary features are depicted. Following these, the methodology and the findings of a study of the policy engagement of Portuguese social work academics are then presented. The findings relate to the levels of engagement in policy and the forms that this takes. The study also offers insights into various factors that are associated with these, such as perceptions, capabilities, institutional support and the accessibility of the policy process. The chapter concludes with an analysis of the findings and their implications.

Introduction: Febrile neutropenia (FN) is a potentially life-threatening complication of systemic chemotherapy (CT) that often requires hospital admission. Delay in diagnosis and treatment are associated with higher morbidity and mortality. Objective: We aimed to determine the factors that influence FN episodes outcomes in the emergency room (ER). Methods: This was a retrospective study of all FN episodes (with a collected blood culture [BC]) that occurred between 2012 and 2016 at our institution. FN was defined as a temperature ≥38°C and an absolute neutrophil count (ANC) Results: Between 2012 and 2016, there were 173 FN episodes in 153/1,947 patients treated with intravenous CT. Most of these episodes (n = 121, 70%) were diagnosed in the ER, 29 in the outpatient clinic, and 23 as inpatients. In the ER, the median time was 36 min from hospital nurse triage to medical observation, and 52 min from medical observation to complete blood count specimen collection. There was a positive BC in 33 FN episodes, 72% with Gram-negative bacteria. A total of 160 FN episodes led to hospital admission and 13 were treated as outpatients. Mortality associated with the FN episode was 15% and an ANC Conclusion: This study confirms that FN is a serious and common complication of IV CT which must be diagnosed and treated promptly. Profound neutropenia was the only predictive factor of mortality.

Background Venous thromboembolism (VTE) is a frequent complication in patients with cancer and causes considerable morbidity and mortality. The risk of VTE is higher in patients with pancreatic cancer and is often associated with treatment delays or interruptions. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing. Patients and methods We conducted a retrospective study to determine the incidence of VTE and to evaluate the ONKOTEV score as a VTE predictive tool in a population of patients with pancreatic cancer. Results Between February 2012 and May 2017, 165 patients were included in the study. The median age was 73 years, 45.5% of patients were female, and 55.8% had stage IV disease. Fifty-one patients had a VTE (30.9%); 23.5% had pulmonary embolism, 25.5% had deep venous thrombosis, and 51.0% had visceral VTE (VsT). At a median follow-up time of 6.3 months, cumulative incidence of VTE was less than 10% for ONKOTEV scores 0 or 1 and approximately 40% and 70% for scores 2 and ≥3, respectively. Conclusion The high VTE incidence observed in this study is consistent with prior reports. Patients at high risk for VTE with no increase in hemorrhagic risk should be considered for primary thromboprophylaxis. The ONKOTEV score may stratify VTE risk in patients with pancreatic cancer, with ONKOTEV score ≥2 being associated with a higher VTE occurrence. Implications for practice Venous thromboembolism (VTE) is a frequent complication of patients with pancreatic cancer and causes considerable morbidity, treatment delays or interruptions, and mortality. Thromboprophylaxis is not used routinely in ambulatory patients. Tools to stratify the risk of VTE are important to help select patients who may benefit from thromboprophylaxis. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing. In this patient series, ONKOTEV score ≥2 was associated with high VTE occurrence and may stratify VTE risk in patients with pancreatic cancer, suggesting that ONKOTEV can be considered to select patients with pancreatic cancer for primary thromboprophylaxis.

This chapter examines, using a historical approach, two lines of research regarding the Progressive Era in the Unites States. The first approach concerns the relationship between social work and social policy. In the first section, the article describes the main features of and lessons from the involvement of social work pioneers in social work and social reform in the context of the public and social policies process. The second dimension analysed focuses more specifically on the methods and strategies adopted by the Settlement Movement, but also by some Charity Organization Societies’ leaders and other social reformers. Both of these approaches also concern the policy formulation and decision-making processes conceptualised and adopted by social reformers in the Progressive Era.

Some 2–5% of germ cell tumours are of extragonadal origin, with a retroperitoneal location being very rare. The majority of retroperitoneal germ cell tumours have metastasized from a testicular tumour. These tumours are diagnosed incidentally or symptomatically and nearly all present with high alpha-fetoprotein and lactate dehydrogenase levels. We describe the unusual case of a 31-year-old man with a yolk-sac, retroperitoneal germ cell tumour, with normal serum alpha-fetoprotein and lactate dehydrogenase levels, which has not previously been described. A testicular tumour was excluded by physical examination and additional tests. Our diagnosis was based on a high level of suspicion and histopathological results. As far as we know, this is the first case described with these characteristics. LEARNING POINTS Extragonadal germ cell tumours are rare but can have fatal consequences if undiagnosed. The usual laboratory markers of the disease were absent in our patient. A high level of suspicion is required for diagnosis and close follow-up is required.

Accumulative Roll Bonding (ARB) was used to fabricate Graphene Oxide-reinforced Al-matrix composites, benefiting from a grain refinement effect of the metal-lic matrix. Graphene Oxide reinforcement was suspended in a stabilized aqueous solution and applied, prior to each ARB cycle, through airgun spraying, in order to obtain a ho-mogeneous distribution. Concentrations of 0.5, 2.5 and 10 mg/ml (graphene ox-ide/millipore water) were used. For each concentration, samples produced have under-gone up to 5 rolling cycles. Optical and electron scanning microscopies were used for microstructural char-acterization of the rolled composites which revealed a non-homogenous deformation of the layers across the composite’s thickness. Although not desired but expected, Alumin-ium oxide formation occurred where the reinforcement was applied. Although the presence of graphene-oxide promoted an increase in the micro-hardness, higher values were obtained with its lowest concentration for the same num-ber of ARB cycles. The number of ARB cycles and the direction of the tested sections also influenced the microhardness results since the 5-cycle samples and the rolling di-rection sections for all the samples achieved higher hardness results. Graphene Oxide revealed to be a major contributor to the increase of stiffness during bending of the test-ed samples. The ARB processed samples revealed a decrease on the electrical conductivity when compared with the annealed Aluminium, since the Graphene Oxide and Alumini-um oxide have insulator properties. The contribution of the reinforcement to this de-crease was only noticeable when using higher concentrations, since the sample with less concentration of the applied Graphene Oxide revealed slightly better results than the sample without any reinforcement.

Relatório final do estágio profissionalizante do 6.º ano

A 56-year-old man with good performance status was diagnosed with plurimetastatic colon adenocarcinoma 1 year before. He is currently under second-line chemotherapy with 5-FU+oxaliplatin (FOLFOX) and bevacizumab. Due to a catheter-related thrombosis, the subclavian vein central venous

In cystic fibrosis (CF), respiratory failure caused by progressive airway obstruction and tissue damage is primarily a result of the aberrant inflammatory responses to lung infections with Pseudomonas aeruginosa. Despite considerable improvement in patient survival, conventional therapies are mainly supportive. Recent progress toward gene therapy for CF has been encouraging; however, several factors such as immune response and transduced cell turnover remain as potential limitations to CF gene therapy. As alternative gene therapy vectors for CF, we examined the feasibility of using recombinant SV40-derived vectors (rSV40s), which may circumvent some of these obstacles. To accommodate the large cystic fibrosis transmembrane conductance regulator (CFTR) cDNA, we removed not only SV40 Tag genes, but also all capsid genes. We, therefore, tested whether 'gutless' rSV40s could be packaged and were able to express a functional human CFTR cDNA. The results from our in vitro analysis determined that rSV40-CFTR was able to successfully result in the expression of CFTR protein, which localized to the plasma membrane and restored channel function to CFTR-deficient cells. Similarly, in vivo experiments delivering rSV40-CFTR to the lungs of Cftr-/- mice resulted in a reduction of the pathology associated with intra-tracheal P. aeruginosa challenge. rSV40-CFTR-treated mice had less weight loss when compared with control-treated mice as well as demonstrably reduced lung inflammation as evidence by histology and reduced inflammatory cytokines in the broncho-alveolar lavage. The reduction in inflammatory cytokine levels led to an evident decrease in neutrophil influx to the airways. These results indicate that further study of the application of rSV40-CFTR to CF gene therapy is warranted.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO FUNDAÇÃO DE APOIO À PESQUISA DO ESTADO DO RIO DE JANEIRO Programar redes de sensores sem fio (RSSF) é uma tarefa difícil. O programador tem que lidar com várias atividades simultâneas em um ambiente com recursos extremamente limitados. Neste trabalho propomos um modelo de programação para facilitar essa tarefa. O modelo que propomos combina o uso de máquinas virtuais configuráveis baseadas em componentes com uma linguagem de script reativa que pode ser analisada estaticamente para evitar conitos de memória e execução de laços infinitos. Essa abordagem permite a exibilidade de carregamento remoto de código nos nós da rede combinado com um conjunto de garantias para o programador. A escolha de um conjunto específico de componentes numa configuração de máquina virtual define o nível de abstração visto pelo script da aplicação. Para avaliar esse modelo, construímos Terra, um sistema que combina a linguagem de script Céu-T com uma máquina virtual e uma biblioteca de componentes. Nós projetamos esta biblioteca considerando as funcionalidades comumente necessárias em aplicações de RSSF - tipicamente para sensoreamento e controle. Implementamos diferentes aplicações utilizando Terra e uma linguagem orientada a eventos baseados em C. Além disso discutimos as vantagens e desvantagens dessas implementações alternativas. Finalmente, também avaliamos Terra medindo o custo adicional em uma aplicação básica e discutimos sua utilização e custo em diferentes cenários de aplicações WSNs. Programming wireless sensors networks (WSN) is a difficult task. The programmer must deal with several concurrent activities in an environment with severely limited resources. In this work we propose a programming model to facilitate this task. The model we propose combines the use of configurable component-based virtual machines with a reactive scripting language which can be statically analyzed to avoid unbounded execution and memory conicts. This approach allows the exibility of remotely uploading code on motes to be combined with a set of guarantees for the programmer. The choice of the specific set of components in a virtual machine configuration defines the abstraction level seen by the application script. To evaluate this model, we built Terra, a system combining the scripting language Céu-T with the Terra virtual machine and a library of components. We designed this library taking into account the functionalities commonly needed in WSN applications - typically for sense and control. We implemented different applications using Terra and using an event-driven language based on C and we discuss the advantages and disadvantages of the alternative implementations. Finally, we also evaluate Terra by measuring its overhead in a basic application and discussing its use and cost in different WSN scenarios.

Many applications of gene delivery require long-term transgene expression. In dividing cells, this result necessitates vector genome persistence, usually by integrating into cellular DNA. Since recombinant gene delivery vectors derived from tag-deleted, replication-incompetent simian virus-40 (SV40) provide for long-term transgene expression in resting and dividing cells, we tested whether such enduring transgene expression reflected integration into cellular genomes. Several lines of evidence suggested this likelihood. After transduction in vitro, continuously dividing cell lines and continuously stimulated primary cells uniformly showed transgene expression for many months. Mice whose livers were transduced in vivo, partially resected, and allowed to regenerate showed comparable levels of transgene expression in regenerated and preoperative livers. Thus, replicationincompetent SV40 vectors (rSV40) persist in vitro and in vivo despite extensive cell division. We tested the possibility that this persistence reflected integration directly. Southern blot analyses of genomic DNA from transduced 293 cells showed that vector genome incorporation into cell DNA happened within days of transduction. Episomal vector DNA was barely detectable 96 hours post-transduction. Inverted PCR, used to characterize vector integration points, showed vector DNA integrated randomly into the cell genome. The circular rSV40 genome opened at different points in each integrand. A significant proportion of the integrands did not contain the entire vector sequence, but rather only portions thereof. Quantitative Southern blot analysis showed approximately 3.05 transgene copies per cell. Therefore, recombinant SV40 gene delivery vectors integrate into the cellular DNA of both resting and dividing cells, and do so randomly and within days of transduction. This integration may explain long-term transgene expression.

Compared with single agents, combination antilentiviral pharmacotherapy targets multiple HIV-1 functions simultaneously, maximizing efficacy and decreasing chances of escape mutations. Combination genetic therapy could theoretically enhance efficacy similarly, but delivery of even single genes to high percentages of hematopoietic cells or their derivatives has proven problematic. Because of their high efficiency of gene delivery, we tested recombinant SV40-derived vectors (rSV40s) for this purpose. We made six rSV40s, each carrying a different transgene that targeted a different lentiviral function. We tested the ability of these constructs, individually and in double and triple combinations, to protect SupT1 human T lymphoma cells from HIV-1 challenge. Single chain antibodies (SFv) against CXCR4 and against HIV-1 reverse transcriptase (RT) and integrase (IN) were used, as were polymeric TAR decoys (PolyTAR) and a dominant-negative mutant of HIV-1 Rev (RevM10). Immunostaining showed that virtually all doubly treated cells expressed both transgenes. All transgenes individually protected from HIV-1 but, except for anti-CXCR4 SFv, their effectiveness diminished as challenge doses increased from 40 through 2500 tissue culture infectious dose(50) (TCID(50))/10(6) cells. However, all combinations of transgenes protected target cells better than individual transgenes, even from the highest challenge doses. Thus, combination gene therapies may inhibit HIV-1 better than single agents, and rSV40s may facilitate delivery of multigene therapeutics.

TCH codes are a class of binary nonlinear cyclic codes that have been used in several systems (e.g. mobile satellite, Ultra-Wideband) for tasks like coding and synchronization. The original generating method of this class of codes restricts the length (or period) of the codewords to the set {2, 4, 16, 256, 65536}. In this paper we use an alternative generation method based on the algebraic properties of Zech logarithms that allow us to generalize the construction in a systematic manner and improving the codeword length choices, code size and minimum distance. The performance of these generalized codewords are then evaluated using both AWGN and Rayleigh communication channels and qualitatively compared with the originally extended TCH codewords.

This paper presents an extension of the ASM (Accelerated Simulation Method) to be able to evaluate the performance of concatenated coding schemes, so as to get similar results to the MCSM (Monte Carlo Simulation Method) more efficiently, i.e. using less time and computational resources. The efficiency of the ASM is particularly useful to estimate the performance of complex or unknown coding schemes, so this optimised method is applied to estimate the performance of various TCH (Tomlinson, Cercas, Hughes) codes concatenated with RS (Reed-Solomon) codes, namely, TCH(16,6,2) with RS(63,45,9) and TCH(32,8,6) with RS(255,223,16). Both SD (Soft-Decision) and HD (Hard-Decision) decoding are considered and the overall performance takes into account modulation and channel conditions.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR Algumas características básicas das redes de sensores sem fio (RSSF) dificultam as tarefas de criação e reconfiguração de aplicações. Nesse trabalho apresentamos um modelo de programação que pretende simplificar essas tarefas. O modelo se baseia no uso conjunto de funções parametrizáveis e de máquinas de estados finitos, e permite a implementação de diferentes tipos de aplicações para redes de sensores sem fio e a configuração remota dessas aplicações. Descrevemos alguns testes para avaliar o quanto esse modelo pode facilitar o desenvolvimento de novas aplicações, o quanto é fácil aplicar novas alterações sobre as aplicaçõesem execuçãos, e o impacto na quantidade de mensagens na rede por conta do uso da configuração remota. Some basic characteristics of wireless sensor networks (WSN) make application creation and reconfiguration dificult tasks. A programming model is presented to simplify these tasks. This model is based on a set of parametrized components and on a Finite State Machine, and allows the remote configuration of different applications over the same set of installed components. We describe some tests to evaluate its impact on the development process, and the ease of applying modifications to a running application. We also measure the additional impact of remote configuration on network activity.

Assinalando os 150 anos do nascimento de Jane Addams e Mary Richmond procura-se neste artigo contribuir para resgatar a relevância da obra e a actualidade do seu pensamento. Com base na noção de «sociatria », introduzida por Richmond, revisitam-se os caminhos da fundação de duas tradições no Serviço Social, com recorrência erigidas como irreconciliáveis, exploram-se as convergências no seu pensamento e acção e apontam-se as possibilidades da sua articulação profícua no actual contexto societário e de intervenção em Serviço Social., In the 150th anniversary of the birth of Jane Addams and Mary Richmond this article aims to rescue the present relevance of their work and thought. Based on the notion of «sociatry», introduced by Richmond, the paper revisits the paths of the founding of two traditions in Social Work, with recurrence erected as irreconcilable, explore the convergences in their thought and action and pointed out the possibilities of its successful articulation in the current societal context and Social Work intervention.

Este artigo ocupa-se da orientação e tendências actuais dos dispositivos de acompanhamento social no âmbito das políticas de assistência social / acção social, focalizando-se na reconfiguração das suas lógicas de acção e especialmente no modus operandi na relação face-a-face com os utentes - beneficiários destes serviços. A abordagem adoptada, das "novas regras do social", inscreve, no plano analítico, a reconfiguração do Estado Social e das políticas sociais nas grandes transformações das sociedades contemporâneas e designadamente no quadro do processo de individuação e da forma como se redesenham as relações entre colectividades e indivíduo em matéria de solidariedade. Neste quadro, analisam-se as diferentes lógicas presentes na trajectória dos dispositivos de acompanhamento social, bem como os desafios e riscos que enfrentam no presente, num contexto societário de instabilidade e incerteza. Fundação para a Ciência e a Tecnologia