Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.This work was financially supported by the project PTDC/CTM-NAN/3547/2014 (POCI-01-0145-FEDER-016639) funded by FEDER funds through the Programa Operacional Competitividade e Internacionalização-COMPETE 2020 and Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia. A.P.S., B.C. and S.D.S. acknowledge FCT for the Ph.D. scholarships (SFRH/BD/137073/2018 and SFRH/BD/145652/2019) and the contract under the Norma Transitória–DL57/2016/CP/CP1360/CT0013, respectively. V.L. acknowledges her contract in the framework of the project NORTE-01-0247-FEDER-033399, funded by FEDER funds through the Sistema de Incentivos à Investigação e Desenvolvimento Tecnológico (SI I&DT), Aviso nº 03/SI/2017, Projetos em Co-promoção do Programa Interfac

Correcção de uma má-oclusão de Classe II divisão 1 em duas fases de tratamento

A influência dos aparelhos funcionais no crescimento craniofacial assim como a filosofia dos tratamentos ortodônticos que envolvem duas fases são assuntos controversos. O tratamento das más-oclusões de Classe II Divisão 1 executado em duas fases visa, na primeira fase diminuir a discrepância sagital. A segunda fase pretende obter uma oclusão de acordo com os padrões de oclusão funcional. O objectivo deste artigo consiste em apresentar a sequência de tratamento de um caso clínico de má-oclusão de Classe II Divisão 1, tratado em duas fases, em que foi utilizado um activador do tipo Teuscher, na primeira fase.The influence of functional appliances on craniofacial growth as well as the two-phase orthodontic treatment philosophy are still controversial subjects. The main purpose of the two-phase treatment involving activators is to promote dento-alveolar changes. The goal of the second phase is creating an occlusion according to functional occlusion patterns. The aim of this article is to present the sequence of a Class II Division 1 treatment case in two phases, in which a Teuscher activator is used in the first phase

Pulmonary Metastasis in a Cardiac Angiosarcoma. Case Report and Discussion

Apresenta-se um caso clínico referente a doente de 35 anos, do sexo masculino sem antecedentes pessoais relevantes, admitido no serviço de urgência por quadro de toracalgia e tosse produtiva com alterações electrocardiográficas sugestivas de pericardite. Inicialmente admitido pelo Serviço de Cardiologia, com melhoria do quadro clínico após terapêutica anti- -inflamatória; contudo, no internamento houve como intercorrência pneumonia de provável etiologia bacteriana, complicada por derrame pleural. Após a alta,foi referenciado à consulta de pneumologia, onde se manteve o estudo etiológico do derrame persistente, tendo vindo a complicar-se o seu quadro com alterações das cavidades cardíacas e múltiplos nódulos pulmonares, sugestivos de endocardite subaguda com embolização séptica pulmonar. Internado no serviço de Pneumologia e submetido a videotoracoscopia, foi-lhe diagnosticado angiossarcoma cardíaco com metastização pulmonar. Assistiu-se a uma rápida evolução do quadro clínico, quase fulminante, com falência cardíaca e óbito do doente sem ter iniciado radioterapia ou quimioterapia adjuvante

Identification of appropriate housekeeping genes for quantitative RT-PCR analysis in MDA-MB-231 and NCI-H460 human cancer cell lines under hypoxia and serum deprivation

Gene expression studies aimed at analyzing cancer cells under hypoxia and serum deprivation conditions show major potential for understanding molecular mechanisms associated with tumor progression as well as resistance to antitumor agents. To the best of our knowledge, a study for the identification of appropriate housekeeping genes in breast and lung cancer cells under hypoxia and serum deprivation conditions is currently missing. Given the relevance of a reliable and accurate normalization, we herein aimed to identify the appropriate housekeeping genes for breast and lung cancer cell lines cultured under hypoxia and/or serum deprivation. The stability of five commonly used housekeeping genes (ACTB, β 2M, GUSB, 18S rRNA, and PPIA) was assessed after reverse-transcription quantitative real-time PCR in MDA-MB-231 and NCI-H460 cancer cell lines using GeNorm, NormFinder and BestKeeper software. GeNorm and NormFinder ranking revealed ACTB, GUSB and PPIA as the most stable genes for both tumor cell lines. Our results support the use of ACTB/PPIA for MDA-MB-231 and GUSB/PPIA for NCI-H460 cells as the most stable combination for normalization of gene expression under hypoxic and serum deprivation conditions. Our results highlight the importance of the selection of the housekeeping genes in cancer cells subjected to different physiological stresses, such as hypoxia and serum deprivation.This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nıvel Superior (CAPES) [grant agreement No. 88881.132780/2016-01]; Fundac ão de Amparoa Ciência e Tecnologia de Pernambuco (FACEPE) [grant agreement No. 0883-2.08/13];and the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie [grant agreement No. 748880]. This work was also funded by the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); and by FEDER—Fundo Europeu de Desenvolvimento Regional funds through COMPETE 2020—Operational 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 the project POCI-01-0145-FEDER-016585 (PTDC/BBB EBI/0567/2014)

Emerging biosensing technologies for neuroinflammatory and neurodegenerative disease diagnostics

Neuroinflammation plays a critical role in the onset and progression of many neurological disorders, including Multiple Sclerosis, Alzheimer’s and Parkinson’s diseases. In these clinical conditions the underlying neuroinflammatory processes are significantly heterogeneous. Nevertheless, a common link is the chronic activation of innate immune responses and imbalanced secretion of pro and anti-inflammatory mediators. In light of this, the discovery of robust biomarkers is crucial for screening, early diagnosis, and monitoring of neurological diseases. However, the difficulty to investigate biochemical processes directly in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory responses have been identified in different body fluids, such as blood, cerebrospinal fluid, and tears. In addition, progress in micro and nanotechnology has enabled the development of biosensing platforms capable of detecting in real-time, multiple biomarkers in clinically relevant samples. Biosensing technologies are approaching maturity where they will become deployed in community settings, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight both clinical and recent technological advances toward the development of multiplex-based solutions for effective neuroinflammatory and neurodegenerative disease diagnostics and monitoring.IM and AC acknowledge the financial support from the Marie Curie COFUND Programme Nano TRAIN for Growth from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 600375. This article is a result of the project Nanotechnology based functional solutions (FEDERNORTE-01-0145-FEDER-000019), co-financed by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PM acknowledges the Ph.D. fellowship from Fundação para a Ci?ncia e Tecnologia, Portugal (PD/BD/105751/2014)

Acute Treatment of Isolated Posterior Cerebral Artery Occlusion: Single Center Experience

Background and objectives: Randomized trials for mechanical thrombectomy (MT) excluded patients with ischemic strokes due to isolated posterior cerebral artery occlusion (IPCAO), and there is no evidence for best acute treatment strategy in these patients. We aimed to assess the effectiveness and safety of MT in acute IPCAO. Methods: We retrospectively analyzed consecutive patients with acute stroke due to IPCAO submitted to MT and/or intravenous thrombolysis (IVT), between 2015-2019. Effectiveness outcomes (recanalization rate, first-pass effect, NIHSS 24h improvement and 3-month Modified Ranking Scale - mRS) and safety outcomes (complications, symptomatic intracranial hemorrhage (SICH) and 3-month mortality) were described and compared between groups. Results: A total of 38 patients were included, 25 underwent MT and 13 had IVT alone. Successful and complete recanalization were achieved in 68% and 52% of MT patients, respectively. NIHSS improvement at 24h was found in 56% of MT patients versus 30.8% of patients submitted to IVT alone (OR [95% CI]=2.86 [0.69-11.82]) and excellent functional outcome at 3 months (mRS≤1) was achieved in 54.2% of MT patients versus 38.5% in the IVT group (OR [95% CI]=1.60 [0.41-6.32]). Complications occurred in 3 (12%) procedures and there were no SICH. Mortality at 3 months was 20% in the MT group and 15.4% in patients submitted to IVT alone. Conclusions: Our results reflect a real-world scenario in a single center and seem to support the recently growing literature showing that MT is a feasible and safe treatment in IPCAO, with favorable effectiveness.info:eu-repo/semantics/publishedVersio

Saúde mental de trabalhadores de setores administrativos de uma empresa de construção civil e estruturas metálicas

El objetivo de este trabajo fue analizar los factores de riesgo para la salud mental de trabajadores de sectores administrativos de una empresa de construcción civil y estructuras metálicas. Entre los datos obtenidos, se destacaron los siguientes factores de riesgo para la salud mental de los trabajadores del estudio: 26 (81,2%) con histórico personal/familiar de enfermedad mental; 21 (65,62%) con incomodidad física en la actividad laboral; 15 (46,8%) con patrón de sueño y reposo alterados; 14 (43,7) relataron exceso de responsabilidad; 7 (21,8%) quejas de ansiedad y 5 (15,6%) alcohólicos. La investigación reveló que tanto el desgaste físico como el mental predisponen a enfermedades profesionalesThis study aimed to analyze risk factors for the mental health of workers from administrative service sections of a civil construction and metal structures company. The following risk factors for mental health were highlighted for the workers who participated in the study: 26 (81,2%) had suffered from mental illness or had cases in the family; 21 (65,62%) complained about physical discomfort at work; 15 (46,8%) revealed altered sleep and rest patterns; 14 (43,7) complained about excess of responsibility; 7 ( 21,8%) reported anxiety and 5 (15,6%) were alcoholics. The research revealed that both physical and mental exhaustion predispose to occupational diseases.O objetivo deste trabalho foi analisar os fatores de risco para a saúde mental de trabalhadores de setores administrativos de uma indústria de construção civil e metálica. Dos dados obtidos, ficaram em destaque os seguintes fatores de risco para a saúde mental dos trabalhadores do estudo: 26 (81,2%) com histórico pessoal/familiar de doença mental; 21 (65,62%) com desconforto físico no trabalho; 15 (46,8%) com padrão de sono e repouso alterados; 14 (43,7) referindo excesso de responsabilidade; 7 (21,8%) com relato de ansiedade e 5 (15,6%) etilismo. A pesquisa revelou que tanto o desgaste físico como o mental predispõem a doenças ocupacionais

Chronic Hepatitis C Treatment in HIV Co-Infection in Portugal: Results from a Cohort OF 2133 Patients Presented by GEPCOI (Portuguese Coinfection Study Group)

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.info:eu-repo/semantics/publishedVersio