Comparing long-term outcomes of children treated with new-onset type 2 diabetes in an outpatient versus inpatient setting: A retrospective chart review.

BACKGROUND: Early identification and management of pediatric type 2 diabetes mellitus (T2DM) is crucial for improving long-term outcomes. This study aimed to assess if the severity of T2DM at presentation, inferred by the location of treatment initiation (inpatient or outpatient), influences long-term clinical outcomes. METHODS: A retrospective chart review was conducted on 116 pediatric T2DM patients. Data on treatment initiation location, initial and subsequent glycated hemoglobin (HbA1c) levels, prescribed insulin, and body mass index were collected from electronic medical records. RESULTS: Of the 116 patients, 69 were initially treated in an inpatient setting, and 47 received outpatient treatment. At treatment initiation, the inpatient group had significantly higher HbA1c levels compared to the outpatient group (p < .001), but 3 years after treatment initiation, no significant difference in HbA1c was observed between the two groups (p = .057). Prescribed insulin dosages were higher in the inpatient group at treatment initiation (p < .001) and remained higher after 3 years (p < 0.003) compared to the outpatient group. CONCLUSIONS: Pediatric patients initially treated in an inpatient setting had poorer glycemic control and higher prescribed insulin dosing at baseline. After 3 years, there was no significant difference in HbA1c levels, but patients treated as inpatients continued to have higher prescribed insulin. These findings suggest that the severity of diabetes at initial presentation may affect long-term clinical outcomes in children with T2DM.

Catalase Detection via Membrane-Based Pressure Sensors.

Membrane-based sensors (MePSs) exhibit remarkable precision and sensitivity in detecting pressure changes. MePSs are commonly used to monitor catalytic reactions in solution, generating gas products crucial for signal amplification in bioassays. They also allow for catalyst quantification by indirectly measuring the pressure generated by the gaseous products. This is particularly interesting for detecting enzymes in biofluids associated with disease onset. To enhance the performance of a MePS, various structural factors influence membrane flexibility and response time, ultimately dictating the device's pressure sensitivity. In this study, we fabricated MePSs using polydimethylsiloxane (PDMS) and investigated how structural modifications affect the Young's modulus (E) and residual stress (σ0) of the membranes. These modifications have a direct impact on the sensors' sensitivity to pressure variations, observed as a function of the volume of the chamber (Σ) or of the mechanical properties of the membrane itself (S). MePSs exhibiting the highest sensitivities were then employed to detect catalyst quantities inducing the dismutation of hydrogen peroxide, producing dioxygen as a gaseous product. As a result, a catalase enzyme was successfully detected using these optimized MePSs, achieving a remarkable sensitivity of (22.7 ± 1.2) µm/nM and a limit of detection (LoD) of 396 pM.

Polymeric Membranes Doped with Halloysite Nanotubes Imaged using Proton Microbeam Microscopy.

Polymeric membranes are useful tools for water filtration processes, with their performance strongly dependent on the presence of hydrophilic dopants. In this study, polyaniline (PANI)-capped aluminosilicate (halloysite) nanotubes (HNTs) are dispersed into polyether sulfone (PES), with concentrations ranging from 0.5 to 1.5 wt%, to modify the properties of the PES membrane. Both undoped and HNT-doped PES membranes are investigated in terms of wettability (static and time-dependent contact angle), permeance, mechanical resistance, and morphology (using scanning electron microscopy (SEM)). The higher water permeance observed for the PES membranes incorporating PANI-capped HNTs is, finally, assessed and discussed vis-à-vis the real distribution of HNTs. Indeed, the imaging and characterization in terms of composition, spatial arrangement, and counting of HNTs embedded within the polymeric matrix are demonstrated using non-destructive Micro Particle Induced X-ray Emission (µ-PIXE) and Scanning Transmission Ion Microscopy (STIM) techniques. This approach not only exhibits the unique ability to detect/highlight the distribution of HNTs incorporated throughout the whole thickness of polymer membranes and provide volumetric morphological information consistent with SEM imaging, but also overcomes the limits of the most common analytical techniques exploiting electron probes. These aspects are comprehensively discussed in terms of practical analysis advantages.

Maternal and Cord Blood Serum Metabolite Associations with Childhood Adiposity and Body Composition Outcomes.

Maternal metabolites influence the size of newborns independently of maternal body mass index (BMI) and glycemia, highlighting the importance of maternal metabolism on offspring outcomes. This study examined associations of maternal metabolites during pregnancy with childhood adiposity, and cord blood metabolites with childhood adiposity using phenotype and metabolomic data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study. The maternal metabolites analyses included 2324 mother-offspring pairs, while the cord blood metabolites analyses included 937 offspring. Multiple logistic and linear regression were used to examine associations between primary predictors, maternal or cord blood metabolites, and childhood adiposity outcomes. Multiple maternal fasting and 1 hr metabolites were significantly associated with childhood adiposity outcomes in Model 1 but were no longer significant after adjusting for maternal BMI and/or maternal glycemia. In the fully adjusted model, fasting lactose levels were negatively associated with child BMI z-scores and waist circumference, while fasting urea levels were positively associated with waist circumference. One-hour methionine was positively associated with fat-free mass. There were no significant associations between cord blood metabolites and childhood adiposity outcomes. Few metabolites were associated with childhood adiposity outcomes after adjusting for maternal BMI and glucose, suggesting that maternal BMI accounts for the association between maternal metabolites and childhood adiposity.

Sunset Yellow Confined in Curved Geometry: A Microfluidic Approach.

The behavior of lyotropic chromonic liquid crystals (LCLCs) in confined environments is an interesting research field that still awaits exploration, with multiple key variables to be uncovered and understood. Microfluidics is a highly versatile technique that allows us to confine LCLCs in micrometric spheres. As microscale networks offer distinct interplays between the surface effects, geometric confinement, and viscosity parameters, rich and unique interactions emerging at the LCLC-microfluidic channel interfaces are expected. Here, we report on the behavior of pure and chiral doped nematic Sunset Yellow (SSY) chromonic microdroplets produced through a microfluidic flow-focusing device. The continuous production of SSY microdroplets with controllable size gives the possibility to systematically study their topological textures as the function of their diameters. Indeed, doped SSY microdroplets produced via microfluidics, show topologies that are typical of common chiral thermotropic liquid crystals. Furthermore, few droplets exhibit a peculiar texture never observed for chiral chromonic liquid crystals. Finally, the achieved precise control of the produced LCLC microdroplets is a crucial step for technological applications in biosensing and anticounterfeiting.

Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Advancements in modelling human blood brain-barrier on a chip.

The human Blood Brain Barrier (hBBB) is a complex cellular architecture separating the blood from the brain parenchyma. Its integrity and perfect functionality are essential for preventing neurotoxic plasma components and pathogens enter the brain. Although vital for preserving the correct brain activity, the low permeability of hBBB represents a huge impediment to treat mental and neurological disorders or to address brain tumors. Indeed, the vast majority of potential drug treatments are unable to reach the brain crossing the hBBB. On the other hand, hBBB integrity can be damaged or its permeability increase as a result of infections or in presence of neurodegenerative diseases. Currentin vitrosystems andin vivoanimal models used to study the molecular/drug transport mechanism through the hBBB have several intrinsic limitations that are difficult to overcome. In this scenario, Organ-on-Chip (OoC) models based on microfluidic technologies are considered promising innovative platforms that combine the handiness of anin vitromodel with the complexity of a living organ, while reducing time and costs. In this review, we focus on recent advances in OoCs for developing hBBB models, with the aim of providing the reader with a critical overview of the main guidelines to design and manufacture a hBBB-on-chip, whose compartments need to mimic the 'blood side' and 'brain side' of the barrier, to choose the cells types that are both representative and convenient, and to adequately evaluate the barrier integrity, stability, and functionality.

A prioridade da saúde mental e trabalho na atenção básica / Work-related mental health actions in primary care / Actuaciones de salud mental relacionada con el trabajo en la atención primaria

A incidência de problemas de saúde mental relacionada ao trabalho desperta interesse de pesquisadores e profissionais da saúde, embora a temática não seja prioritária na atenção básica. Poucas pesquisas descrevem os processos subjacentes à determinação das prioridades de saúde. Objetivou-se verificar a prioridade dada ao tema, e a sua relação com razões e concepções de profissionais de saúde subjacentes aos processos de implementação de políticas e ações de saúde do trabalhador e saúde mental relacionada ao trabalho na atenção básica. Trata-se de estudo qualitativo realizado com utilização de entrevistas com gestores e profissionais de saúde, analisado por meio de análise de conteúdo. Identificou-se que a saúde mental relacionada ao trabalho não é prioridade. Isto se deve, em parte, à escassez de informações, divisão rígida entre planejamento e execução de ações, e precarização das condições de trabalho. Os resultados indicam caminhos para aprimoramento das ações nesta área em nível municipal (AU).

The incidence of work-related mental health problems arouses the interest of researchers and health professionals, although the issue is not a priority in primary care. Little research describes the processes underlying the determination of health priorities. The objective was to verify the priority given to the theme, and its relationship with reasons and conceptions of health professionals underlying the processes of implementation of policies and actions of workers' health and mental health related to work in primary care. This is a qualitative study carried out using interviews with managers and health professionals, analyzed using content analysis. It was identifiedthat work-related mental health is not a priority. This is due, in part, to the scarcity of information, rigid division between planning and execution of actions, and precarious working conditions. The results indicate ways to improve actions in this areaat the municipal level (AU).

La incidencia de problemas de salud mental relacionados con el trabajo despierta interés de investigadores y profesionales de salud, aunque el tema no sea prioridad en atención primaria. Pocasinvestigacionesdescribe los procesos subyacentes a la determinación de prioridades de salud. El objetivo fue verificar la prioridad otorgada al tema y su relación con razones y concepciones de profesionales de salud que fundamentan los procesos de implementación de políticas y acciones de salud de trabajadores y salud mental relacionadas con el trabajo en atención primaria. Se trata de estudio cualitativo realizado congestores y profesionales de la salud, analizado mediante análisis de contenido. Se identificó que la salud mental relacionada con el trabajo no es prioridad. Esto se debe a la escasez de información, rígida división entre planificación y ejecución de acciones y precarias condiciones laborales. Los resultados indican formas de mejorar las acciones en esta área a nivel municipal (AU).

MEED: A novel robust contrast enhancement procedure yielding highly-convergent thresholding of biofilm images.

Morphological and statistical investigation of biofilm images may be even more critical than the image acquisition itself, in particular in the presence of morphologically complex distributions, due to the unavoidable impact of the measurement technique too. Hence, digital image pre-processing is mandatory for reliable feature extraction and enhancement preliminary to segmentation. Also, pattern recognition in automated deep learning (both supervised and unsupervised) models often requires a preliminary effective contrast-enhancement. However, no universal consensus exists on the optimal contrast enhancement approach. This paper presents and discusses a new general, robust, reproducible, accurate and easy to implement contrast enhancement procedure, briefly named MEED-procedure, able to work on images with different bacterial coverages and biofilm structures, coming from different imaging instrumentations (herein stereomicroscope and transmission microscope). It exploits a proper succession of basic morphological operations (erosion and dilation) and a horizontal line structuring element, to minimize the impact on size and shape of the even finer bacterial features. It systematically enhances the objects of interest, without histogram stretching and/or undesirable artifacts yielded by common automated methods. The quality of the MEED-procedure is ascertained by segmentation tests which demonstrate its robustness regarding the determination of threshold and convergence of the thresholding algorithm. Extensive validation tests over a rich image database, comparison with the literature and comprehensive discussion of the conceptual background support the superiority of the MEED-procedure over the existing methods and demonstrate it is not a routine application of morphological operators.

Impact of SARS-CoV2 on youth onset type 2 diabetes new diagnoses and severity.

INTRODUCTION: Initial reports show an increase in youth onset type 2 diabetes during the COVID-19 pandemic. We aim to expand on existing evidence by analyzing trends over a longer period. OBJECTIVES: Our study aims to describe change in the amount, severity, and demographics of youth onset type 2 diabetes diagnoses during the COVID-19 pandemic compared to the five years before. METHODS: We performed a retrospective cross-sectional review of youth (age ≤ 21) diagnosed with type 2 diabetes during the COVID-19 pandemic (1 May 2020-30 April 2021) and the five years before (1 May 2015-30 April 2020) at a tertiary care center. Children were identified by International Classification of Diseases codes. Charts were reviewed to confirm diagnosis. Chi-square, t tests, and Fisher's exact tests were used for analyses. RESULTS: In the prepandemic era annual diagnoses of type 2 diabetes ranged from 41-69 (mean = 54.2), whereas during the pandemic period 159 children were diagnosed, an increase of 293%. The increase resulted in a higher incidence rate ratio during the pandemic than before, 2.77 versus 1.07 (p = .006). New diagnoses increased most, by 490%, in Non-Hispanic Black patients. The average HbA1c at presentation was higher during the pandemic (9.5% ± 2.6) (79.9 mmol/mol ± 28.2) than before (8.7%±2.1) (72.1 mmol/mol ± 23.1) (p = .003). Of those diagnosed during the pandemic, 59% were tested for COVID-19 and three tested positive. CONCLUSIONS: New diagnoses of type 2 diabetes increased during the pandemic, most notably in Non-Hispanic Black youth. There was not a significant correlation found with clinical or biochemical COVID-19 infection in those tested.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Potential of CO2-laser processing of quartz for fast prototyping of microfluidic reactors and templates for 3D cell assembly over large scale.

Carbon dioxide (CO2)-laser processing of glasses is a versatile maskless writing technique to engrave micro-structures with flexible control on shape and size. In this study, we present the fabrication of hundreds of microns quartz micro-channels and micro-holes by pulsed CO2-laser ablation with a focus on the great potential of the technique in microfluidics and biomedical applications. After discussing the impact of the laser processing parameters on the design process, we illustrate specific applications. First, we demonstrate the use of a serpentine microfluidic reactor prepared by combining CO2-laser ablation and post-ablation wet etching to remove surface features stemming from laser-texturing that are undesirable for channel sealing. Then, cyclic olefin copolymer micro-pillars are fabricated using laser-processed micro-holes as molds with high detail replication. The hundreds of microns conical and square pyramidal shaped pillars are used as templates to drive 3D cell assembly. Human Umbilical Vein Endothelial Cells are found to assemble in a compact and wrapping way around the micro-pillars forming a tight junction network. These applications are interesting for both Lab-on-a-Chip and Organ-on-a-Chip devices.

Long-term follow-up of children with in utero exposure to sulfonylurea medications.

BACKGROUND: Offspring born to mothers with gestational diabetes mellitus (GDM) are more likely to have negative neurodevelopmental health outcomes, early obesity, type 2 diabetes, and metabolic syndrome in childhood, adolescence, and adulthood. Standard of care management for GDM and type 2 diabetes mellitus during pregnancy is insulin, but oral sulfonylurea use is increasing, and these medications cross the placenta. Literature on treatment with sulfonylureas for maternal GDM has focused on maternal glycemic control and neonatal outcomes. Studies that have evaluated the long-term outcomes of children exposed to sulfonylureas in utero are limited. OBJECTIVE: This study evaluated anthropometric and neurodevelopmental outcomes of 55 children (ages 5-10) born to mothers with diabetes during pregnancy treated with sulfonylurea or insulin. METHODS AND RESULTS: A group of 25 sulfonylurea-exposed and 30 insulin-exposed participants were age- and sex-matched between groups. No significant differences were identified in z-scores for body mass index (BMI), waist circumference, skinfold measurements, and body fat or rates of overweight/obese BMI between groups. On performance-based cognitive assessment, the sulfonylurea-exposed group had significantly lower scores on inhibition (p = 0.043). CONCLUSION: In summary, children with in utero sulfonylurea exposure had similar physical measurements compared to children with insulin exposure and lower performance on a measure of executive function (inhibition), which is associated with adverse health outcomes.

O trabalho como determinante da saúde e espaço de desenvolvimento de competências / Work as a health determinant and a place for competence development / El trabajo como factor determinante de la salud y un espacio para el desarrollo de habilidades

Partindo da relação do trabalho com a saúde e com o desenvolvimento de competências profissionais, este artigo objetivou investigar em documentos oficiais das políticas de saúde do município de Vitória-ES de que forma a dimensão trabalho se expressa como determinante da saúde e como espaço de desenvolvimento de competências. A pesquisa, de abordagem qualitativa, apoiou-se em referenciais teóricos sobre competências e saúde do trabalhador e utilizou a análise lexical com uso do software Iramuteq para o tratamento dos dados. Os resultados apontam que: a) o trabalho é negligenciado como determinante da saúde, porém reconhecido como espaço para desenvolvimento de competências profissionais; b) há uma preocupação central com a organização dos serviços de saúde nos documentos analisados; e c) há necessidade de maior destaque ao trabalho como determinante social da saúde em documentos oficiais de saúde para fortalecer e promover práticas de saúde do trabalhador em âmbito municipal.

Starting from the relationship between work and health and the development of professional skills, this article aimed to investigate in official documents of the health policies of the municipality of Vitória-ES how the dimension of work is expressed as a determinant of health, and as a place of competence development. The research, with a qualitative approach, was based on theoretical references on competencies and occupational health, and used lexical analysis with Iramuteq software for data treatment. The results show that (a) work is neglected as a determinant of health, but recognized as a space for the development of professional skills; (b) there is a central concern with the organization of health services in the analyzed documents, and (c) there is a need for greater emphasis on work as a social determinant of health in official health documents, to strengthen and promote worker health practices at the municipal level.

Considerando la relación del trabajo con la salud y con el desarrollo de las capacidades profesionales, el objetivo de este artículo fue investigar en documentos oficiales de política sanitaria del municipio de Vitória-ES cómo la dimensión laboral es un factor determinante de la salud y un espacio de desarrollo de competencias. La investigación, de enfoque cualitativo, se basó en referencias teóricas sobre competencias y salud de trabajadores y utilizó el análisis lexical realizado por el software Iramuteq para el tratamiento de los datos. Los resultados indican que: a) se desconsidera el trabajo como determinante de la salud, pero se lo reconoce como espacio para el desarrollo de las competencias profesionales; b) existe una preocupación central con la organización de los servicios de salud en los documentos analizados; y c) en documentos oficiales de salud, hay que poner más énfasis en que el trabajo es un factor determinante social de la salud, para fortalecer y promover prácticas de salud de los trabajadores en el ámbito municipal.

Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study: newborn anthropometrics and childhood glucose metabolism.

AIMS/HYPOTHESIS: We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity. METHODS: Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study. RESULTS: In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (ß = 1.388; 95% CI 0.870, 1.906; p < 0.001; ß = 0.792; 95% CI 0.340, 1.244; p < 0.001, for birthweight and SSF higher by 1 SD, respectively) in the primary model, while SSF, but not birthweight, was positively associated with the disposition index, a measure of beta cell compensation for insulin resistance (ß = 0.034; 95% CI 0.012, 0.056; p = 0.002). Cord C-peptide levels were inversely associated with Matsuda index (ß = -0.746; 95% CI -1.188, -0.304; p < 0.001 for cord C-peptide higher by 1 SD) in the primary model. CONCLUSIONS/INTERPRETATION: This study demonstrates that higher birthweight and SSF are associated with greater childhood insulin sensitivity and lower glucose levels following a glucose load, associations that were further strengthened after adjustment for maternal glucose levels during pregnancy. Graphical abstract.

Hyperglycemia During Pregnancy and Long-Term Offspring Outcomes.

PURPOSE OF REVIEW: This review will focus on the long-term outcomes in offspring exposed to in utero hyperglycemia and gestational diabetes (GDM), including obesity, adiposity, glucose metabolism, hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and puberty. RECENT FINDINGS: There is evidence, mostly from observational studies, that offspring of GDM mothers have increased risk of obesity, increased adiposity, disorders of glucose metabolism (insulin resistance and type 2 diabetes), and hypertension. In contrast, evidence from the two intervention studies of treatment of mild GDM and childhood measures of BMI, adiposity, and glucose tolerance do not demonstrate that GDM treatment significantly reduces adverse childhood metabolic outcomes. Thus, more evidence is needed to understand the impact of maternal GDM on offspring's adiposity, glucose metabolism, lipid metabolism, risk of fatty liver disease, and pubertal onset. Offspring of GDM mothers may have increased risk for metabolic and cardiovascular complications. Targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism is one potential strategy to prevent adverse metabolic health outcomes.

Lab-on-Chip for Exosomes and Microvesicles Detection and Characterization.

Interest in extracellular vesicles and in particular microvesicles and exosomes, which are constitutively produced by cells, is on the rise for their huge potential as biomarkers in a high number of disorders and pathologies as they are considered as carriers of information among cells, as well as being responsible for the spreading of diseases. Current methods of analysis of microvesicles and exosomes do not fulfill the requirements for their in-depth investigation and the complete exploitation of their diagnostic and prognostic value. Lab-on-chip methods have the potential and capabilities to bridge this gap and the technology is mature enough to provide all the necessary steps for a completely automated analysis of extracellular vesicles in body fluids. In this paper we provide an overview of the biological role of extracellular vesicles, standard biochemical methods of analysis and their limits, and a survey of lab-on-chip methods that are able to meet the needs of a deeper exploitation of these biological entities to drive their use in common clinical practice.

An SPR based immunoassay for the sensitive detection of the soluble epithelial marker E-cadherin.

Protein biomarkers are important diagnostic tools for cancer and several other diseases. To be validated in a clinical context, a biomarker should satisfy some requirements including the ability to provide reliable information on a pathological state by measuring its expression levels. In parallel, the development of an approach capable of detecting biomarkers with high sensitivity and specificity would be ideally suited for clinical applications. Here, we performed an immune-based label free assay using Surface Plasmon Resonance (SPR)-based detection of the soluble form of E-cadherin, a cell-cell contact protein that is involved in the maintaining of tissue integrity. With this approach, we obtained a specific and quantitative detection of E-cadherin from a few hundred microliters of serum of breast cancer patients by obtaining a 10-fold enhancement in the detection limit over a traditional colorimetric ELISA.

Highly Sensitive Membrane-Based Pressure Sensors (MePS) for Real-Time Monitoring of Catalytic Reactions.

Functional, flexible, and integrated lab-on-chips, based on elastic membranes, are capable of fine response to external stimuli, so to pave the way for many applications as multiplexed sensors for a wide range of chemical, physical and biomedical processes. Here, we report on the use of elastic thin membranes (TMs), integrated with a reaction chamber, to fabricate a membrane-based pressure sensor (MePS) for reaction monitoring. In particular, the TM becomes the key-element in the design of a highly sensitive MePS capable to monitor gaseous species production in dynamic and temporally fast processes with high resolution and reproducibility. Indeed, we demonstrate the use of a functional MePS integrating a 2 µm thick polydimethylsiloxane TM by monitoring the dioxygen evolution resulting from catalytic hydrogen peroxide dismutation. The operation of the membrane, explained using a diffusion-dominated model, is demonstrated on two similar catalytic systems with catalase-like activity, assembled into polyelectrolyte multilayers capsules. The MePS, tested in a range between 2 and 50 Pa, allows detecting a dioxygen variation of the µmol L-1 s-1 order. Due to their structural features, flexibility of integration, and biocompatibility, the MePSs are amenable of future development within advanced lab-on-chips.