A simple microfluidic device for the deformability assessment of blood cells in a continuous flow

Blood flow presents several interesting phenomena in microcirculation that can be used to develop microfluidic devices capable to promote blood cells separation and analysis in continuous flow. In the last decade there have been numerous microfluidic studies focused on the deformation of red blood cells (RBCs) flowing through geometries mimicking microvessels. In contrast, studies focusing on the deformation of white blood cells (WBCs) are scarce despite this phenomenon often happens in the microcirculation. In this work, we present a novel integrative microfluidic device able to perform continuous separation of a desired amount of blood cells, without clogging or jamming, and at the same time, capable to assess the deformation index (DI) of both WBCs and RBCs. To determine the DI of both WBCs and RBCs, a hyperbolic converging microchannel was used, as well as a suitable image analysis technique to measure the DIs of these blood cells along the regions of interest. The results show that the WBCs have a much lower deformability than RBCs when subjected to the same in vitro flow conditions, which is directly related to their cytoskeleton and nucleus contents. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to simultaneously separate and assess blood cells deformability.The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/ 2215/2013 from FCT (Fundação para a Ciência e a Tecnologia), COMPETE, QREN and European Union (FEDER). R. O. Rodrigues, D. Pinho and V. Faustino acknowledge respectively, the PhD scholarships SFRH/BD/97658/2013, SFRH/BD/89077/2012 and SFRH/BD/99696/ 2014 granted by FCT. The authors would also like to thank Dr. Ângela Fernandes for providing the blood samples and Dr. Ricardo Calhelha for supplying the tissue culture medium used in this work.info:eu-repo/semantics/publishedVersio

Low cost microfluidic device for partial cell separation: micromilling approach

Several studies have already demonstrated that it is possible to perform blood flow studies in microfluidic systems fabricated by using low-cost techniques. However, most of these techniques do not produce microchannels smaller than 100 microns and as a result they have several limitations related to blood cell separation. Recently, manufacturers have been able to produce milling tools smaller than 100 microns, which consequently have promoted the ability of micromilling machines to fabricate microfluidic devices able to perform separation of red blood cells (RBCs) from plasma. In this work, we show the ability of a micromilling machine to manufacture microchannels with dimensions down to 30 microns. Additionally, we show for the first time the ability of the proposed microfluidic device to enhance the cell-free layer close to the walls, leading to perform partial separation of RBCs from plasma.The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/2010 and EXPL/EMSSIS/2215/2013 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER). RR and DP acknowledge, respectively, the PhD scholarships SFRH/BD/97658/2013 and SFRH/BD/89077/2012 attributed by FCT.info:eu-repo/semantics/publishedVersio

A rapid and low-cost nonlithographic method to fabricate biomedical microdevices for blood flow analysis

Microfluidic devices are electrical/mechanical systems that offer the ability to work with minimal sample volumes, short reactions times, and have the possibility to perform massive parallel operations. An important application of microfluidics is blood rheology in microdevices, which has played a key role in recent developments of lab-on-chip devices for blood sampling and analysis. The most popular and traditional method to fabricate these types of devices is the polydimethylsiloxane (PDMS) soft lithography technique, which requires molds, usually produced by photolithography. Although the research results are extremely encouraging, the high costs and time involved in the production of molds by photolithography is currently slowing down the development cycle of these types of devices. Here we present a simple, rapid, and low-cost nonlithographic technique to create microfluidic systems for biomedical applications. The results demonstrate the ability of the proposed method to perform cell free layer (CFL) measurements and the formation of microbubbles in continuous blood flow.The authors acknowledge the financial support provided by PTDC/SAU-BEB/105650/2008, PTDC/SAU-ENB/116929/2010, EXPL/EMS-SIS/2215/2013 and scholarship SFRH/BD/89077/2012 and SFRH/BD/97658/2013 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER).info:eu-repo/semantics/publishedVersio

Microfluidic deformability study of an innovative blood analogue fluid based on giant unilamellar vesicles

Blood analogues have long been a topic of interest in biofluid mechanics due to the safety and ethical issues involved in the collection and handling of blood samples. Although the current blood analogue fluids can adequately mimic the rheological properties of blood from a macroscopic point of view, at the microscopic level blood analogues need further development and improvement. In this work, an innovative blood analogue containing giant unilamellar vesicles (GUVs) was developed to mimic the flow behavior of red blood cells (RBCs). A natural lipid mixture, soybean lecithin, was used for the GUVs preparation, and three different lipid concentrations were tested (1 × 10−3 M, 2 × 10−3 M and 4 × 10−3 M). GUV solutions were prepared by thin film hydration with a buffer, followed by extrusion. It was found that GUVs present diameters between 5 and 7 µm which are close to the size of human RBCs. Experimental flow studies of three different GUV solutions were performed in a hyperbolic-shaped microchannel in order to measure the GUVs deformability when subjected to a homogeneous extensional flow. The result of the deformation index (DI) of the GUVs was about 0.5, which is in good agreement with the human RBC’s DI. Hence, the GUVs developed in this study are a promising way to mimic the mechanical properties of the RBCs and to further develop particulate blood analogues with flow properties closer to those of real blood.COMPETE2020, NORTE2020, PORTUGAL2020, FEDER; FCT Project PTDC/QEQ-FTT/4287/2014 (POCI-01-0145-FEDER-016861); FCT Project PTDC/EMD-EMD/29394/2017 (NORTE-01-0145-FEDER-029394); FCT Project PTDC/EME-SIS/30171/2017 (NORTE-01-0145-FEDER-000032); FCT Project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020); SFRH/BD/99696/2014 PhD Grant;info:eu-repo/semantics/publishedVersio

Social representations of people with mental health problems resulting from the use of alcohol and other drugs / Representações sociais de pessoas com problemas de saúde mental decorrentes do uso de álcool e outras drogas

Objetivo: compreender as representações sociais de pessoas com problemas de saúde mental decorrentes do uso de álcool e outras drogas que frequentam os Narcóticos Anônimos. Método: trata-se de um estudo descritivo-exploratório, com enfoque qualitativo, empregando as Representações Sociais para a temática da pesquisa, em que foram implementadas as etapas do Consolidated Criteria for Reporting Qualitative Research. Resultados: as informações obtidas foram transformadas em três unidades temáticas: as Representações Sociais de pessoas com problemas de saúde mental decorrentes do uso de álcool e outras drogas; Representações Sociais de álcool e outras drogas: doença da adicção; frequentar Narcóticos Anônimos significa liberdade, uma autoavaliação e aceitação. Considerações finais: a compreensão das representações sociais e suas implicações na obtenção da abstinência, possibilita atuar mediante às especificidades de cada sujeito, partindo de uma abordagem integral considerando-se as percepções acerca de sua condição, vivências e contexto no qual está inserido.

Social representations of the family caregiver about palliative care in terminal patient / Representações sociais do cuidador familiar sobre cuidados paliativos em paciente terminal

Objective: to analyze the social representations of family caregivers about palliative care in patients with serious, progressive disease that threatens the continuity of their lives. Method: the study was descriptive, using a qualitative approach. For the interpretation of the results, the Theory of Social Representations, created by Serge Moscovici and Denise Jodelet, was used as a theoretical contribution. The research was carried out with 30 family caregivers of patients with end-of-life cancer. Data collection was carried out through semi-structured interviews and the thematic analysis technique. Results: after analyzing the data, three categories emerged: common sense and cancer; palliative care, the patient and caregivers and caregivers and their social representation. Final considerations: the social representations of the family caregiver made it possible to identify the true extent of daily issues in the professional routine.Objetivo: analizar las representaciones sociales de los cuidadores familiares sobre los cuidados paliativos en pacientes con enfermedad grave y progresiva que amenaza la continuidad de sus vidas. Método: el estudio fue descriptivo, con abordaje cualitativo. Para la interpretación de los resultados se utilizó como aporte teórico la Teoría de las Representaciones Sociales, creada por Serge Moscovici y Denise Jodelet. La investigación se llevó a cabo con 30 cuidadores familiares de pacientes con cáncer al final de la vida. La recolección de datos se realizó a través de entrevistas semiestructuradas y la técnica de análisis temático. Resultados: después del análisis de los datos surgieron tres categorías: sentido común y cáncer; cuidados paliativos, el paciente y los cuidadores y los cuidadores y su representación social. Consideraciones finales: las representaciones sociales del cuidador familiar permitieron identificar la verdadera extensión de las cuestiones cotidianas en el cotidiano profesional.Objetivo: analisar as representações sociais dos cuidadores familiares sobre os cuidados paliativos em pacientes com doença grave, progressiva e que ameaça a continuidade de sua vida. Método: o estudo foi do tipo descritivo, utilizando abordagem qualitativa. Para a interpretação dos resultados foi empregado como aporte teórico a Teoria das Representações Sociais, criada por Serge Moscovici e Denise Jodelet. A pesquisa foi realizada com 30 cuidadores familiares de pacientes com câncer em estágio final de vida. A coleta foi feita por meio da entrevista semiestruturada e a técnica de análise temática. Resultados: após a análise dos dados, emergiram três categorias: o senso comum e o câncer; os cuidados paliativos, o doente e os cuidadores e os cuidadores e sua representação social. Considerações finais: as representações sociais do cuidador familiar possibilitaram identificar a verdadeira extensão das questões diárias no cotidiano profissional.

Social representations about the health and disease process in catholic belief / Representações sociais sobre o processo de saúde e doença na crença católica

Introduction: religiosity is observed in everyday life and should be considered when providing care, because each religion expresses different ideologies. The study aimed to describe the social representations of Catholic patients and analyze the implications of their imaginary for the health-disease process. Method: descriptive study, with qualitative approach. Carried out in an oncology hospital, having as participants self-declared Catholic people. Semi-structured interviews and a technique of free word association were used for data collection. Results: three thematic units emerged: The representation of the disease for Catholic christians; The Catholic religion as a foundation in the process of illness; Representation of the disease for Catholics: diseases acquired by breaking the laws of God. Final considerations: religiosity is a significant part of people's daily lives and should be respected regardless of the professional's belief.Introducción: la religiosidad se observa en la vida cotidiana y debe tenerse en cuenta a la hora de prestar cuidados, porque cada religión expresa ideologías diferentes. El estudio tuvo como objetivo describir las representaciones sociales de los pacientes católicos y analizar las implicaciones de su imaginario para el proceso salud-enfermedad. Método: estudio descriptivo, con enfoque cualitativo. Realizado en un hospital oncológico, teniendo como participantes personas autodeclaradas católicas. Para la recolección de datos se utilizaron entrevistas semiestructuradas y una técnica de asociación libre de palabras. Resultados: surgieron tres unidades temáticas: La representación de la enfermedad para los cristianos católicos; La religión católica como fundamento en el proceso de la enfermedad; Representación de la enfermedad para los católicos: enfermedades adquiridas por la ruptura de las leyes de Dios. Consideraciones finales: la religiosidad es una parte importante de la vida cotidiana de las personas y debe ser respetada independientemente de la creencia del profesional.Objetivo: estudo objetivou descrever as representações sociais de pacientes católicos e analisar as implicações do seu imaginário para o processo saúde-doença. Método: estudo descritivo, com abordagem qualitativa. Realizado em um hospital oncológico, tendo como participantes pessoas autodeclaradas católicas. Utilizou-se entrevista semiestruturada e técnica de livre associação de palavras para coleta de dados. Resultados: emergiram três unidades temáticas: A representação da doença para cristões católicos; A religião católica como alicerce no processo de adoecimento; Representação da doença para católicos: enfermidades adquiridas por infringirmos as leis de Deus. Considerações finais: a religiosidade é parte significativa no cotidiano das pessoas e deve ser respeitada independente da crença do profissional.

Organ-on-a-chip platforms for drug screening and delivery in tumor cells: a systematic review

The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.This work has been supported by the projects NORTE-01-0145-FEDER-030171 (project reference PTDC/EME-SIS/30171/2017), NORTE-01-0145-FEDER-029394 (project reference PTDC/EMDEMD/29394/2017), through the COMPETE2020, the Lisb@2020, the Programa Operacional Regional do Norte–Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (FEDER) and by Fundação para a Ciência e Tecnologia (FCT), and through FEDER and FCT, project references EXPL/EMD-EMD/0650/2021 and PTDC/EEI-EEE/2846/2021. The authors also acknowledge the partial financial support within the R&D Units Project Scope: UIDB/00319/2020, UIDB/04077/2020, UIDB/00690/2020, UIDB/04436/2020. This work was also funded by AMED-CREST Grant Number JP20gm1310001h0002. Raquel O. Rodrigues (R.O.R.) thanks FCT for her contract funding provided through 2020.03975.CEECIND

The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses

Rationale: Several human and experimental studies have shown that early life adverse events can shape physical and mental health in adulthood. Stress or elevated levels of glucocorticoids (GCs) during critical periods of development seem to contribute for the appearance of neurospyschiatric conditions such as anxiety and depression, albeit the underlying mechanisms remain to be fully elucidated. Objectives: The aim of the present study was to determine the long-term effect of prenatal erxposure to dexamethasone- DEX (synthetic GC widely used in clinics) in fear and anxious behavior and identify the neurochemical, morphological and molecular correlates. Results: Prenatal exposure to DEX triggers a hyperanxious phenotype and altered fear behavior in adulthood. These behavioral traits were correlated with increased volume of the bed nucleus of the stria terminalis (BNST), particularly the anteromedial subivision which presented increased dendritic length; in parallel, we found an increased expression of synapsin and NCAM in the BNST of these animals. Remarkably, DEX effects were opposite in the amygdala, as this region presented reduced volume due to significant dendritic atrophy. Albeit no differences were found in dopamine and its metabolite levels in the BNST, this neurotransmitter was substantially reduced in the amygdala, which also presented an up-regulation of dopamine receptor 2. Conclusions: Altogether our results show that in utero DEX exposure can modulate anxiety and fear behavior in parallel with significant morphological, neurochemical and molecular changes; importantly, GCs seem to differentially affect distinct brain regions involved in this type of behaviors.This study was supported by a grant from the Institute for the Study of Affective Neuroscience (ISAN). AJR is supported by a Fundação para a Ciência e Tecnologia (FCT) grant

Red blood cells radial dispersion in blood flowing through microchannels: the role of temperature

The behavior of suspensions of individual blood cells, such as red blood cells (RBCs), flowing through microvessels and microfluidic systems depend strongly on the hematocrit (Hct), microvessel topology and cell properties. Although it is well known that blood rheological properties are temperature dependent, to the best of our knowledge no work has studied the role of the temperature on the RBCs dispersion. A powerful way to investigate this latter effect is through a high-speed video microscopy system, which provides detailed flow measurements of each individual RBC. Hence, the effect of temperature on the RBCs dispersion flowing through a 100μm glass capillary was examined by means of a confocal micro-PTV system. Hundreds of labeled RBCs were tracked at moderate Hct (12%) and at four different temperatures, i.e., 25°C, 32°C, 37°C and 42°C. The results yielded an enhancement of the RBCs diffusion as the temperature increases. Hence, our findings show that RBCs radial dispersion is temperature dependent and as a result the temperature should not be ignored in future blood flow studies. We believe that this finding is important for a better understanding of blood mass transport mechanisms under both physiological and pathological conditions.The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/2215/2013 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER). R. O. Rodrigues, D. Pinho and V. Faustino acknowledge respectively, the PhD scholarships SFRH/BD/97658/ 2013, SFRH/BD/89077/2012 and SFRH/BD/99696/2014 Granted by FCT. The authors are also very grateful to Professor Takuji Ishikawa and Professor Takami Yamaguchi (Tohoku University) for supporting this research work.info:eu-repo/semantics/publishedVersio