Assessing the influence of perfusion on cardiac microtissue maturation: A heart-on-chip platform embedding peristaltic pump capabilities.

Heart-on-chip is an unprecedented technology for recapitulating key biochemical and biophysical cues in cardiac pathophysiology. Several designs have been proposed to improve its ability to mimic the native tissue and establish it as a reliable research platform. However, despite mimicking one of most vascularized organs, reliable strategies to deliver oxygen and substrates to densely packed constructs of metabolically demanding cells remain unsettled. Herein, we describe a new heart-on-chip platform with precise fluid control, integrating an on-chip peristaltic pump, allowing automated and fine control over flow on channels flanking a 3D cardiac culture. The application of distinct flow rates impacted on temporal dynamics of microtissue structural and transcriptional maturation, improving functional performance. Moreover, a widespread transcriptional response was observed, suggesting flow-mediated activation of critical pathways of cardiomyocyte structural and functional maturation and inhibition of cardiomyocyte hypoxic injury. In conclusion, the present design represents an important advance in bringing engineered cardiac microtissues closer to the native heart, overcoming traditional bulky off-chip fluid handling systems, improving microtissue performance, and matching oxygen and energy substrate requirements of metabolically active constructs, avoiding cellular hypoxia. Distinct flow patterns differently impact on microtissue performance and gene expression program.

Modality transition on renal replacement therapy and quality of life of patients: a 10-year follow-up cohort study.

PURPOSE: Despite advance in renal replacement therapy (RRT), patients with chronic end-stage renal disease (ESRD) face various limitations, and renal transplantation (Tx) is the treatment that impacts most on quality of life (QoL). This study aimed to assess changes in QoL in a cohort of ESRD dialysis patients. METHODS: Sociodemographic, clinical, nutritional, lifestyle, and QoL data were collected from 712 patients at baseline (time 1) and after 10 years of follow-up (time 2) for patients surviving. The QoL was assessed through the 36-Item Short Form Health Survey (SF-36) and the multiple linear regression model was used to analyze the factors associated with change in QoL. RESULTS: A total of 205 survivors were assessed and distributed into three groups according to current RRT (Dialysis-Dialysis, Dialysis-Tx, and Dialysis-Tx-Dialysis). At time 1, only age was significantly different among groups; at time 2, transplant patients sustained greater social participation, job retention, and improvement in SF-36 scores. The factors associated with change in QoL were more time on dialysis interfering negatively on physical functioning (p = 0.002), role-physical limitations (p  = 0.002), general health (p  = 0.007), social functioning (p = 0.02), role-emotional (p = 0.003), and physical components ( p = 0.002); non-participation in social groups at times 1 and 2 reducing vitality (p = 0.02) scores; and having work at time 2, increasing vitality (p = 0.02) and mental health (p  = 0.02) scores. CONCLUSIONS: QoL was shown to be dynamic throughout the years of RRT, transplantation being the treatment with more benefits to the ESRD. More time on dialysis and limited social and occupational routine were associated with a reduction in QoL.

Yeasts identification in microfluidic devices using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH).

Peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) is a highly specific molecular method widely used for microbial identification. Nonetheless, and due to the detection limit of this technique, a time-consuming pre-enrichment step is typically required before identification. In here we have developed a lab-on-a-chip device to concentrate cell suspensions and speed up the identification process in yeasts. The PNA-FISH protocol was optimized to target Saccharomyces cerevisiae, a common yeast that is very relevant for several types of food industries. Then, several coin-sized microfluidic devices with different geometries were developed. Using Computational fluid dynamics (CFD), we modeled the hydrodynamics inside the microchannels and selected the most promising options. SU-8 structures were fabricated based on the selected designs and used to produce polydimethylsiloxane-based microchips by soft lithography. As a result, an integrated approach combining microfluidics and PNA-FISH for the rapid identification of S. cerevisiae was achieved. To improve fluid flow inside microchannels and the PNA-FISH labeling, oxygen plasma treatment was applied to the microfluidic devices and a new methodology to introduce the cell suspension and solutions into the microchannels was devised. A strong PNA-FISH signal was observed in cells trapped inside the microchannels, proving that the proposed methodology works as intended. The microfluidic designs and PNA-FISH procedure described in here should be easily adaptable for detection of other microorganisms of similar size.

Building partnerships in education through a story-tool based intervention: Parental involvement experiences among families with Roma backgrounds.

Introduction: School educators are likely to explain the poor educational trajectories of students with Roma backgrounds related to the lack of parental support and interest in children's education. Aiming to understand further the patterns of Roma group's parental involvement in children's school life and their engagement experiences in school-related activities, the current research set an intervention supported by a culturally sensitive story-tool. Method: Grounded in the intervention-based research framework, 12 participants (i.e., mothers) from different Portuguese Roma groups participated in this study. Data was collected through interviews conducted pre-and postintervention. Eight weekly sessions were delivered in the school context, using a story-tool and hands- on activities to generate culturally significant meanings regarding attitudes, beliefs, and values toward children's educational trajectories. Results: Through the lens of acculturation theory, data analysis provided important findings under two overarching topics: patterns of parental involvement in children's school life and participants' engagement in the intervention program. Discussion: Data show the distinct ways Roma parents participate in children's education and the relevance of mainstream contexts providing an atmosphere likely to build collaborative relationships with parents to overcome barriers to parental involvement.

Shining a Light on Cancer-Photonics in Microfluidic Tumor Modeling and Biosensing.

Microfluidic platforms represent a powerful approach to miniaturizing important characteristics of cancers, improving in vitro testing by increasing physiological relevance. Different tools can manipulate cells and materials at the microscale, but few offer the efficiency and versatility of light and optical technologies. Moreover, light-driven technologies englobe a broad toolbox for quantifying critical biological phenomena. Herein, the role of photonics in microfluidic 3D cancer modeling and biosensing from three major perspectives is reviewed. First, optical-driven technologies are looked upon, as these allow biomaterials and living cells to be manipulated with microsized precision and present opportunities to advance 3D microfluidic models by engineering cancer microenvironments' hallmarks, such as their architecture, cellular complexity, and vascularization. Second, the growing field of optofluidics is discussed, exploring how optical tools can directly interface microfluidic chips, enabling the extraction of relevant biological data, from single fluorescent signals to the complete 3D imaging of diseased cells within microchannels. Third, advances in optical cancer biosensing are reviewed, focusing on how light-matter interactions can detect biomarkers, rare circulating tumor cells, and cell-derived structures such as exosomes. Photonic technologies' current challenges and caveats in microfluidic 3D cancer models are overviewed, outlining future research avenues that may catapult the field.

High-performance delignification of invasive tree species wood with ionic liquid and deep eutectic solvent for the production of cellulose-based polyelectrolytes.

An efficient and eco-friendly process for lignocellulosic biomass fractionation is essential for the production of high value-added bioproducts from biomass. The present work aimed to obtain cellulose-rich materials from the wood of an invasive tree species (Acacia dealbata) using an appropriate choice of ionic liquids (ILs) and deep eutectic solvents (DESs), and of the processing conditions, for the subsequent production of cationic wood-based polyelectrolytes. In the pretreatment step, the 1-butyl-3-methylimidazolium methyl sulfate (IL) + H2O and choline chloride + imidazole (DES) systems demonstrated a remarkable ability to remove lignin from acacia, reaching up to 92.4 and 90.2% of delignification, respectively. However, the DES pretreatment revealed to be more selective for lignin removal with lower cellulose losses (less than 15%) than the IL treatment (up to 30%) and less cellulose depolymerization. The hemicellulose was also removed but in a lesser extent with the DES treatment. Both systems could provide treated materials with a very high cellulose content (≥89%). Afterwards, cationic polyelectrolytes having a considerable content of quaternary ammonium groups (up to 3.6 mmol g-1) were obtained directly from the IL- and DES-pretreated woods. The treated woods, when used as raw materials for cationization reaction, allow to synthesize water-soluble polyelectrolytes with potential to be applied in wastewater treatment, pharmaceutical or cosmetic products.

[Timely outpatient treatment of cervical cancer: the influence of region of residence for women in the state of Minas Gerais, Brazil]. / Tratamento ambulatorial do câncer do colo do útero em tempo oportuno: a influência da região de residência de mulheres no Estado de Minas Gerais, Brasil.

This study aimed to investigate whether there is an association between the Extended Health Regions (EHR) of residence in the state of Minas Gerais, Brazil, and the interval between diagnosis and start of treatment for women who underwent outpatient treatment (chemotherapy or radiotherapy) for cervical cancer by the Brazilian Unified National Health System (SUS), between 2001 and 2015. This is a cross-sectional study, part of a cohort with 8,857 women. Negative binomial regression models were used to evaluate the association of EHR of residence and the interval between diagnosis and start of treatment (in days), considering a significance level of 5%. The models were constructed using blocks of sociodemographic, clinical, and treatment-related covariates. It was found that the EHR of residence of women is associated with the interval between diagnosis and start of treatment. The northern EHR was the region of the state where the average time to start treatment was lower, and not residing in this EHR increases the average time to start treatment between 24% and 93% compared to other EHRs in the state. The disparity in the interval between diagnosis and start of treatment between the regions of Minas Gerais is evident. The availability of services enabled for the treatment of cancer in the EHRs does not necessarily results in a greater agility for the start of treatment. Understanding the flows of Oncology Care Networks and their regional differences is essential to improve public policies that ensure compliance with current laws, such as Law n. 12,732/2012, which recommends the start of treatment for cancer patients within 60 days after diagnosis.

O objetivo deste estudo é investigar se há associação entre as Regiões Ampliadas de Saúde (RAS) de residência de Minas Gerais, Brasil, e o intervalo entre diagnóstico e início de tratamento de mulheres que realizaram tratamento ambulatorial (quimioterapia ou radioterapia) para câncer do colo do útero pelo Sistema Único de Saúde (SUS), entre 2001 e 2015. Trata-se de um estudo transversal, recorte de uma coorte, com 8.857 mulheres. Para avaliar a associação da RAS de residência e o intervalo entre diagnóstico e início de tratamento (em dias), foram utilizados modelos de regressão binomial negativa, considerando nível de significância de 5%. Os modelos foram construídos usando blocos de covariáveis sociodemográficas, clínicas e relacionadas ao tratamento. Foi determinado que a RAS de residência das mulheres está associada ao intervalo entre o diagnóstico e o início de tratamento. A RAS Norte foi a região do estado onde a média de tempo para iniciar o tratamento foi menor, e não residir nessa RAS aumenta a média de tempo para iniciar o tratamento entre 24% e 93% em comparação com outras RAS do estado. Fica evidente a disparidade no intervalo entre diagnóstico e início de tratamento entre as regiões do Estado de Minas Gerais. A disponibilidade de serviços habilitados para o tratamento do câncer nas RAS não reflete necessariamente em maior agilidade para início de tratamento. Compreender os fluxos das Redes de Atenção Oncológica e suas diferenças regionais é fundamental para aprimorar políticas públicas que garantam o cumprimento de leis vigentes, como a Lei nº 12.732/2012, que preconiza o início do tratamento de pacientes com câncer em até 60 dias após o diagnóstico.

El objetivo de este estudio es investigar si existe una asociación entre las Regiones Ampliadas de Salud (RAS) de residencia en Minas Gerais, Brasil, y el intervalo entre el diagnóstico y el inicio del tratamiento para mujeres que realizaron tratamiento ambulatorio (quimioterapia o radioterapia) para cáncer de cuello uterino por el Sistema Único de Salud (SUS) entre 2001 y 2015. Se trata de un estudio transversal, recortado de una cohorte, con 8.857 mujeres. Para evaluar la asociación entre la RAS de residencia y el intervalo entre el diagnóstico y el inicio del tratamiento (en días), se utilizaron modelos de regresión binomial negativa, considerando el nivel de significancia del 5%. Los modelos se construyeron utilizando bloques de covariables sociodemográficas, clínicas y relacionadas con el tratamiento. Se encontró una asociación entre la RAS de residencia de las mujeres y el intervalo entre el diagnóstico y el inicio del tratamiento. La región de la RAS Norte tuvo tiempo promedio más corto para el inicio del tratamiento, pero si las mujeres no residen en esta RAS el tiempo promedio para el inicio del tratamiento puede aumentar entre el 24% y el 93% en comparación con otras RAS del estado. Queda evidente la disparidad del intervalo entre el diagnóstico y el inicio del tratamiento entre las regiones de Minas Gerais. La disponibilidad de servicios habilitados para el tratamiento del cáncer en la RAS no necesariamente refleja la mayor rapidez para el inicio del tratamiento. Es fundamental comprender los flujos de las Redes de Atención Oncológica y sus diferencias regionales para buscar mejorar las políticas públicas que garantizan el cumplimiento de la legislación vigente, como la Ley nº 12.732/2012, que recomienda que el tratamiento de los pacientes con cáncer debe empezar dentro de los 60 días posteriores al diagnóstico.

Functional microvascularization of human myocardium in vitro.

In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research.

Quality of life of patients with cancer undergoing chemotherapy in hospitals in Belo Horizonte, Minas Gerais State, Brazil: does individual characteristics matter?

This study aims to evaluate changes in quality of life of cancer patients at the beginning of the first and the second cycle of chemotherapy (CT) in hospitals in Belo Horizonte, Minas Gerais State, Brazil. Longitudinal, prospective, descriptive study with a quantitative approach. We enrolled 230 patients, from a broader cohort, diagnosed with the five most frequent types of cancer (breast, colorectal, cervical, lung, and head and neck), aged 18 years or older, who were initiating CT for the first time. quality of life was assessed with the EORTC QLQ-C30 version 3, applied at the beginning of the first and second chemotherapy cycle. The paired Wilcoxon test was used to identify differences in quality of life between the two time points. A multivariate linear regression analysis was performed using the bootstrap method to investigate potential predictors of global health Status/quality of life. There was a significant increase in patients' emotional function scores (p < 0.001) as well as symptom scores for pain (p = 0.026), diarrhea (p = 0.018), and nausea/vomiting (p < 0.001) after initiation of CT. Widowhood was associated with improvements in the global health Status/quality of life (p = 0.028), whereas the presence of cervical cancer (p = 0.034) and being underweight (p = 0.033) were related to poorer global health status/quality of life scores. CT has detrimental effects on patients' physical health but, on the other hand, it leads to improvements in the emotional domain. Patients' individual characteristics at the beginning of CT are associated with changes in their quality of life. Our study could help identify these characteristics.

Comorbidities and in-hospital death of viral pneumonia adults admitted to SUS (2002-2015).

OBJECTIVE: To identify demographic and clinical characteristics of adult patients hospitalized in the Brazilian Unified Health System (SUS) due to viral pneumonia and investigate the association between some comorbidities and death during hospitalization. METHODS: This retrospective cohort study was conducted with secondary data of adults admitted to SUS due to viral pneumonia between 2002 and 2015. Patient profile was characterized based on demographic and clinical variables. The association between the ten Elixhauser comorbidities and in-hospital death was investigated using Poisson regression models with robust standard errors. Results were quantified as incidence rate ratio (IRR) with 95% confidence intervals (CI), and we built five models using successive inclusion of variables blocks. RESULTS: Hospital admissions for viral pneumonias decreased throughout the study period, and it was observed that 5.8% of hospitalized patients had an in-hospital death. We observed significant differences in demographic and clinical characteristics by comparing individuals who died during hospitalization with those who did not, with the occurrence of one or more comorbidities being more expressive among patients who died. Although not considered risk factors for in-hospital death, chronic pulmonary disease and congestive heart failure were the most common comorbidities. Conversely, IRR for in-hospital death increased with other neurological disorders, diabetes, cancer, obesity, and especially with HIV/AIDS. CONCLUSIONS: Individuals presenting with pulmonary and cardiovascular diseases require proper attention during hospitalization, as well as those with other neurological diseases, diabetes, cancer, obesity, and especially HIV/AIDS. Understanding the influence of chronic diseases on viral infections may support the healthcare system in achieving better outcomes.

Micro-electrode channel guide (µECG) technology: an online method for continuous electrical recording in a human beating heart-on-chip.

Cardiac toxicity still represents a common adverse outcome causing drug attrition and post-marketing withdrawal. The development of relevantin vitromodels resembling the human heart recently opened the path towards a more accurate detection of drug-induced human cardiac toxicity early in the drug development process. Organs-on-chip have been proposed as promising tools to recapitulatein vitrothe key aspects of thein vivocardiac physiology and to provide a means to directly analyze functional readouts. In this scenario, a new device capable of continuous monitoring of electrophysiological signals from functionalin vitrohuman hearts-on-chip is here presented. The development of cardiac microtissues was achieved through a recently published method to control the mechanical environment, while the introduction of a technology consisting in micro-electrode coaxial guides allowed to conduct direct and non-destructive electrophysiology studies. The generated human cardiac microtissues exhibited synchronous spontaneous beating, as demonstrated by multi-point and continuous acquisition of cardiac field potential, and expression of relevant genes encoding for cardiac ion-channels. A proof-of-concept pharmacological validation on three drugs proved the proposed model to potentially be a powerful tool to evaluate functional cardiac toxicity.

Myasthenia gravis and pregnancy: anaesthetic management--a series of cases.

BACKGROUND AND OBJECTIVE: Myasthenia gravis is an autoimmune neuromuscular disease, usually affecting women in the second and third decades. The course is unpredictable during pregnancy and puerperium. Myasthenia gravis can cause major interference in labour and partum and exacerbations of the disease frequently occur. The aim of this series of cases is to analyse retrospectively the anaesthetic management of myasthenia gravis patients and complications during the peripartum period. MATERIALS AND METHODS: Retrospective, single centre study from clinical files of female myasthenia gravis patients who delivered between 1985 and 2007 at Hospital de Santo António, Porto, Portugal. RESULTS: Seventeen myasthenia gravis patients delivered between 1985 and 2007 in Hospital Santo António. Two women were not included in the study as they had a spontaneous abortion in the first trimester. Four patients presented exacerbations of the disease during pregnancy, no exacerbation occurred in eight patients and three patients presented their first symptoms of myasthenia gravis during pregnancy (without diagnosis at time of delivery). Concerning the eight patients without exacerbations of the disease during pregnancy, pregnancy was brought to term in 87.5% of the cases; five women were submitted to nonurgent caesarean section (62.5%); and epidural block was performed in six patients (75%). No complications related to anaesthesia occurred in the peripartum period. Concerning the four patients with exacerbations of the disease, pregnancy was brought to term in three cases (75%); three women were submitted to nonurgent caesarean section (75%); and epidural block was performed in three patients (75%). One patient underwent an uncomplicated thymectomy under general anaesthesia during pregnancy and, in the postpartum period, there was a myasthenic crisis in another patient. Concerning the three patients without a myasthenia gravis diagnosis at partum, one woman already being followed for presenting muscular weakness had a vaginal delivery under epidural block, without complications; another patient, presenting discrete supine dyspnoea, was submitted to elective caesarean section under spinal block and developed severe dyspnoea that required mechanical ventilation and ICU admission; and in the remaining case, a woman presenting mild blurred vision was submitted to general anaesthesia, which resulted in delayed emergence, muscular weakness and respiratory failure. Pregnancy went full term in all cases (100%). No newborn had a myasthenic crisis. CONCLUSION: Myasthenia gravis can interfere slightly with pregnancy and partum, although exacerbations of the disease occur frequently. Strict surveillance and therapeutic optimisation are crucial. In women with controlled disease, caesarean section should be carried out only if there are obstetric reasons. Locoregional anaesthesia is preferred, mainly epidural block. A good multidisciplinary cooperation, specific precautions and surveillance can certainly contribute to an improved outcome in myasthenia gravis patients during the peripartum period.

Preterm birth prevention.

Preterm birth (PTB), which occurs in about 12% of pregnancies worldwide, is the main cause of neonatal morbidity and mortality. Symptomatic treatment of pregnancies presenting in preterm labor with corticosteroids and antibiotics has improved neonatal outcomes but has not reduced the incidence of PTB. Evidence suggests that the rate of PTB may be reduced by the prophylactic use of progesterone in women with a previous history of preterm delivery and in those with a short cervical length identified by routine transvaginal ultrasound. This review summarizes the evidence (level A evidence) of the effectiveness of progesterone on the rate of PTB.

Promoting Reminiscences with Virtual Reality Headsets: A Pilot Study with People with Dementia.

This study aimed to explore the feasibility and effects of promoting reminiscences, using virtual reality (VR) headsets for viewing 360° videos with personal relevance, with people with dementia. A study with a mixed methods design was conducted with nine older adults diagnosed with dementia. Interventions consisted of four sessions, in which the participants' engagement, psychological and behavioral symptoms, and simulation sickness symptoms were evaluated. Neuropsychiatric symptomatology and quality of life were measured pre- and post-intervention. Caregivers were interviewed regarding the effect of the approach. In most cases, participants appeared to enjoy the sessions, actively explored the 360° environment, and shared memories associated with the depicted locations, often spontaneously. There were no cases of significant increases in simulator sickness and psychological and behavioral symptoms during sessions, with only some instances of minor eyestrain, fullness of head, anxiety, irritability, and agitation being detected. Although there were no significant changes in the measured outcomes after intervention, the caregivers assessed the experience as potentially beneficial for most participants. In this study, promoting reminiscences with VR headsets was found to be a safe and engaging experience for people with dementia. However, future studies are required to better understand the added value of immersion, using VR, in reminiscence therapy.

Stage at diagnosis and stage-specific survival of breast cancer in Latin America and the Caribbean: A systematic review and meta-analysis.

BACKGROUND: Female breast cancer is the most common cancer in Latin American and Caribbean (LAC) countries and is the leading cause of cancer deaths. The high mortality-to-incidence ratio in the regions is associated with mainly the high proportion of advanced stage diagnosis, and also to inadequate access to health care. In this study we aimed to systematically review the proportion of advanced stage (III-IV) at diagnosis (pas) and the five-year stage-specific survival estimates of breast cancer in LAC countries. METHODS: We searched MEDLINE, Embase, and LILACS (Latin American and Caribbean Health Science Literature) to identify studies, in any language, indexed before Nov 5, 2018. We also conducted manual search by reviewing citations of papers found. pas was summarized by random effects model meta-analysis, and meta-regression analysis to identify sources of variation. Stage-specific survival probabilities were described as provided by study authors, as it was not possible to conduct meta-analysis. PROSPERO CRD42017052493. RESULTS: For pas we included 63 studies, 13 of which population-based, from 22 countries comprising 221,255 women diagnosed from 1966 to 2017. The distribution of patients by stage varied greatly in LAC (pas 40.8%, 95%CI 37.0% to 44.6%; I2 = 99%; p<0.0001). The heterogeneity was not explained by any variable included in the meta-regression. There was no difference in pas among the Caribbean (pas 43.0%, 95%CI 33.1% to 53.6%), Central America (pas 47.0%, 95%CI 40.4% to 53.8%) and South America (pas 37.7%, 95%CI 33.1% to 42.5%) regions. For 5-year stage-specific survival we included 37 studies, comprising 28,988 women from ten countries. Seven of these studies were included also for pas. Since we were unable to adjust for age, comparability between countries and regions was hampered, and as expected, the results varied widely from study to study. CONCLUSIONS: LAC countries should look to address concerns with early detection and diagnosis of breast cancer, and wherever viable implement screening programs and to provide timely treatment.

Generation of functional cardiac microtissues in a beating heart-on-a-chip.

With the increasing attention on cardiovascular disorders and the current inability of pre-clinical models to accurately predict human physiology, the need for advanced and reliable heart in vitro models is paramount. Microfabrication technologies provide potential solutions in the organs-on-chip systems: microengineered devices where cell cultures can be hosted and cultured to develop three-dimensional models or microtissues with high similarity to human physiology. We here described the fabrication and operation procedures for a beating heart-on-a-chip. The device features a culture region for a 3D cardiac microtissue and a system for applying tuned mechanical stimulation during culture to improve cardiac development. We additionally describe procedures for characterizing tissue maturation via immunofluorescence and functional evaluations of microtissue contractility.

A microscale biomimetic platform for generation and electro-mechanical stimulation of 3D cardiac microtissues.

Organs-on-chip technology has recently emerged as a promising tool to generate advanced cardiac tissue in vitro models, by recapitulating key physiological cues of the native myocardium. Biochemical, mechanical, and electrical stimuli have been investigated and demonstrated to enhance the maturation of cardiac constructs. However, the combined application of such stimulations on 3D organized constructs within a microfluidic platform was not yet achieved. For this purpose, we developed an innovative microbioreactor designed to provide a uniform electric field and cyclic uniaxial strains to 3D cardiac microtissues, recapitulating the complex electro-mechanical environment of the heart. The platform encompasses a compartment to confine and culture cell-laden hydrogels, a pressure-actuated chamber to apply a cyclic uniaxial stretch to microtissues, and stainless-steel electrodes to accurately regulate the electric field. The platform was exploited to investigate the effect of two different electrical stimulation patterns on cardiac microtissues from neonatal rat cardiomyocytes: a controlled electric field [5 V/cm, or low voltage (LV)] and a controlled current density [74.4 mA/cm2, or high voltage (HV)]. Our results demonstrated that LV stimulation enhanced the beating properties of the microtissues. By fully exploiting the platform, we combined the LV electrical stimulation with a physiologic mechanical stretch (10% strain) to recapitulate the key cues of the native cardiac microenvironment. The proposed microbioreactor represents an innovative tool to culture improved miniaturized cardiac tissue models for basic research studies on heart physiopathology and for drug screening.

Tratamento ambulatorial do câncer do colo do útero em tempo oportuno: a influência da região de residência de mulheres no Estado de Minas Gerais, Brasil / Timely outpatient treatment of cervical cancer: the influence of region of residence for women in the state of Minas Gerais, Brazil / Tratamiento ambulatorio del cáncer de cuello uterino en un tiempo adecuado: la influencia de la región de residencia de las mujeres en el estado de Minas Gerais, Brasil

O objetivo deste estudo é investigar se há associação entre as Regiões Ampliadas de Saúde (RAS) de residência de Minas Gerais, Brasil, e o intervalo entre diagnóstico e início de tratamento de mulheres que realizaram tratamento ambulatorial (quimioterapia ou radioterapia) para câncer do colo do útero pelo Sistema Único de Saúde (SUS), entre 2001 e 2015. Trata-se de um estudo transversal, recorte de uma coorte, com 8.857 mulheres. Para avaliar a associação da RAS de residência e o intervalo entre diagnóstico e início de tratamento (em dias), foram utilizados modelos de regressão binomial negativa, considerando nível de significância de 5%. Os modelos foram construídos usando blocos de covariáveis sociodemográficas, clínicas e relacionadas ao tratamento. Foi determinado que a RAS de residência das mulheres está associada ao intervalo entre o diagnóstico e o início de tratamento. A RAS Norte foi a região do estado onde a média de tempo para iniciar o tratamento foi menor, e não residir nessa RAS aumenta a média de tempo para iniciar o tratamento entre 24% e 93% em comparação com outras RAS do estado. Fica evidente a disparidade no intervalo entre diagnóstico e início de tratamento entre as regiões do Estado de Minas Gerais. A disponibilidade de serviços habilitados para o tratamento do câncer nas RAS não reflete necessariamente em maior agilidade para início de tratamento. Compreender os fluxos das Redes de Atenção Oncológica e suas diferenças regionais é fundamental para aprimorar políticas públicas que garantam o cumprimento de leis vigentes, como a Lei nº 12.732/2012, que preconiza o início do tratamento de pacientes com câncer em até 60 dias após o diagnóstico.

This study aimed to investigate whether there is an association between the Extended Health Regions (EHR) of residence in the state of Minas Gerais, Brazil, and the interval between diagnosis and start of treatment for women who underwent outpatient treatment (chemotherapy or radiotherapy) for cervical cancer by the Brazilian Unified National Health System (SUS), between 2001 and 2015. This is a cross-sectional study, part of a cohort with 8,857 women. Negative binomial regression models were used to evaluate the association of EHR of residence and the interval between diagnosis and start of treatment (in days), considering a significance level of 5%. The models were constructed using blocks of sociodemographic, clinical, and treatment-related covariates. It was found that the EHR of residence of women is associated with the interval between diagnosis and start of treatment. The northern EHR was the region of the state where the average time to start treatment was lower, and not residing in this EHR increases the average time to start treatment between 24% and 93% compared to other EHRs in the state. The disparity in the interval between diagnosis and start of treatment between the regions of Minas Gerais is evident. The availability of services enabled for the treatment of cancer in the EHRs does not necessarily results in a greater agility for the start of treatment. Understanding the flows of Oncology Care Networks and their regional differences is essential to improve public policies that ensure compliance with current laws, such as Law n. 12,732/2012, which recommends the start of treatment for cancer patients within 60 days after diagnosis.

El objetivo de este estudio es investigar si existe una asociación entre las Regiones Ampliadas de Salud (RAS) de residencia en Minas Gerais, Brasil, y el intervalo entre el diagnóstico y el inicio del tratamiento para mujeres que realizaron tratamiento ambulatorio (quimioterapia o radioterapia) para cáncer de cuello uterino por el Sistema Único de Salud (SUS) entre 2001 y 2015. Se trata de un estudio transversal, recortado de una cohorte, con 8.857 mujeres. Para evaluar la asociación entre la RAS de residencia y el intervalo entre el diagnóstico y el inicio del tratamiento (en días), se utilizaron modelos de regresión binomial negativa, considerando el nivel de significancia del 5%. Los modelos se construyeron utilizando bloques de covariables sociodemográficas, clínicas y relacionadas con el tratamiento. Se encontró una asociación entre la RAS de residencia de las mujeres y el intervalo entre el diagnóstico y el inicio del tratamiento. La región de la RAS Norte tuvo tiempo promedio más corto para el inicio del tratamiento, pero si las mujeres no residen en esta RAS el tiempo promedio para el inicio del tratamiento puede aumentar entre el 24% y el 93% en comparación con otras RAS del estado. Queda evidente la disparidad del intervalo entre el diagnóstico y el inicio del tratamiento entre las regiones de Minas Gerais. La disponibilidad de servicios habilitados para el tratamiento del cáncer en la RAS no necesariamente refleja la mayor rapidez para el inicio del tratamiento. Es fundamental comprender los flujos de las Redes de Atención Oncológica y sus diferencias regionales para buscar mejorar las políticas públicas que garantizan el cumplimiento de la legislación vigente, como la Ley nº 12.732/2012, que recomienda que el tratamiento de los pacientes con cáncer debe empezar dentro de los 60 días posteriores al diagnóstico.

Microfabricated Physiological Models for In Vitro Drug Screening Applications.

Microfluidics and microfabrication have recently been established as promising tools for developing a new generation of in vitro cell culture microdevices. The reduced amounts of reagents employed within cell culture microdevices make them particularly appealing to drug screening processes. In addition, latest advancements in recreating physiologically relevant cell culture conditions within microfabricated devices encourage the idea of using such advanced biological models in improving the screening of drug candidates prior to in vivo testing. In this review, we discuss microfluidics-based models employed for chemical/drug screening and the strategies to mimic various physiological conditions: fine control of 3D extra-cellular matrix environment, physical and chemical cues provided to cells and organization of co-cultures. We also envision future directions for achieving multi-organ microfluidic devices.