Microfluidics for Advanced Drug Delivery Systems.

Considerable efforts have been devoted towards developing effective drug delivery methods. Microfluidic systems, with their capability for precise handling and transport of small liquid quantities, have emerged as a promising platform for designing advanced drug delivery systems. Thus, microfluidic systems have been increasingly used for fabrication of drug carriers or direct drug delivery to a targeted tissue. In this review, the recent advances in these areas are critically reviewed and the shortcomings and opportunities are discussed. In addition, we highlight the efforts towards developing smart drug delivery platforms with integrated sensing and drug delivery components

Detecting Emerging Technologies in Artificial Intelligence Scientific Ecosystem Using an Indicator-based Model

Early identification of emergent topics is of eminent importance due to their potential impacts on society. There are many methods for detecting emerging terms and topics, all with advantages and drawbacks. However, there is no consensus about the attributes and indicators of emergence. In this study, we evaluate emerging topic detection in the field of artificial intelligence using a new method to evaluate emergence. We also introduce two new attributes of collaboration and technological impact which can help us use both paper and patent information simultaneously. Our results confirm that the proposed new method can successfully identify the emerging topics in the period of the study. Moreover, this new method can provide us with the score of each attribute and a final emergence score, which enable us to rank the emerging topics with their emergence scores and each attribute score

Impact of Vitamin E Supplementation on Blood Pressure and Hs-CRP in Type 2 Diabetic Patients

Background: Type 2 diabetes mellitus (T2DM) is a major public health problem worldwide.Hypertension and inflammation are well recognized as risk factors for the macrovascular complicationsof diabetes. The aim of this study was to assess the impact of vitamin E supplementationon blood pressure (BP), serum high-sensitivity C-reactive protein (hs-CRP) and fasting bloodglucose in patients with T2DM.Methods: In a double blind, randomized, controlled clinical trial, 83 patients with T2DM weredivided randomly into two groups of vitamin E (400 mg/d, n=42) and placebo (n=41). All patientsreceived the pearls for 8 weeks. Baseline and eighth week BP, serum hs-CRP, fasting bloodglucose, anthropometric and dietary intake data were obtained from each patient. Data were analyzedusing SPSS version 11.5.Results: Vitamin E supplementation significantly increased serum levels of vitamin E (P <0.001) and decreased mean arterial pressure and fasting blood glucose (P = 0.047, P = 0.028, respectively)in vitamin E group as compared with placebo group. A significant decrease in systolicblood pressure and diastolic blood pressure was observed in the vitamin E group comparing withbaseline values (all P < 0.01). There were no significant changes in serum hs-CRP in both of thestudied groups.Conclusion: Vitamin E had beneficial effects on serum vitamin E, BP and blood glucose in patientswith T2DM. Improvement in BP and glucose control may contribute to reducing complicationsof diabetes including cardiovascular risk in these patients

Role of ROCK isoforms in regulation of stiffness induced myofibroblast differentiation in lung fibrosis

Fibrosis is a major cause of progressive organ dysfunction in several chronic pulmonary diseases. Rho associated coiled-coil forming kinase (ROCK) has shown to be involved in myofibroblast differentiation driven by altered matrix stiffness in fibrotic state. There are two known ROCK isoforms in human, ROCK1 (ROKβ) and ROCK2 (ROKα), but specific role of each isoform in myofibroblast differentiation in lung fibrosis remains unknown. To study this, we developed a Gelatin methacryloyl (GelMA) hydrogel based culture system with different stiffness levels relevant to healthy and fibrotic lungs. We have shown that stiff matrix and not soft matrix, can induce myofibroblast differentiation with high αSMA expression. Furthermore, our data confirm that the inhibition of ROCK signalling by a pharmacological inhibitor (i.e. Y27632) attenuates stiffness induced αSMA expression and fibre assembly in myofibroblasts. To assess the role of ROCK isoforms in this process we used siRNA to knock down the expression of each isoform. Our data showed that knocking down either ROCK1 or ROCK2 did not result in a reduction in αSMA expression in myofibroblasts on stiff matrix as opposed to soft matrix where αSMA expression was reduced significantly. Paradoxically, on stiff matrix, the absence of one isoform (particularly ROCK2) exaggerated αSMA expression and led to thick fibre assembly. Moreover complete loss of αSMA fibre assembly was seen only in the absence of both ROCK isoforms suggesting that both isoforms are implicated in this process. Overall our results indicate the differential role of ROCK isoforms in myofibroblast differentiation on soft and stiff matrices

A paper-based in vitro model for on-chip investigation of the human respiratory system

Culturing cells at the air–liquid interface (ALI) is essential for creating functional in vitro models of lung tissues. We present the use of direct-patterned laser-treated hydrophobic paper as an effective semi-permeable membrane, ideal for ALI cell culture. The surface properties of the paper are modified through a selective CO2 laser-assisted treatment to create a unique porous substrate with hydrophilic regions that regulate fluid diffusion and cell attachment. To select the appropriate model, four promising hydrophobic films were compared with each other in terms of gas permeability and long-term strength in an aqueous environment (wet-strength). Among the investigated substrates, parchment paper showed the fastest rate of oxygen permeability (3 times more than conventional transwell cell culture membranes), with the least variation in its dry and wet tensile strengths (124 MPa and 58 MPa, remaining unchanged after 7 days of submersion in PBS).The final paper-based platform provides an ideal, robust, and inexpensive device for generating monolayers of lung epithelial cells on-chip in a high-throughput fashion for disease modelling and in vitro drug testing

The Comparison of Biomechanical Volar and Dorsal Plating in Distal Part Radius Fractures; a Finite Element Analysis Study

Objective: To compare the stability of the radius stabilized fractured parts by volar and dorsal planting based on modeling approach. Methods: Ten forearm models were created based on Computed Tomography (CT) Scan images by using of Mimics software. The distal part fracture of radius was induced in the models. The stress were developed and implanted in various parts of the bone and and their displacement were evaluated in volar and dorsal inserted implants. Results: The results of this study showed that the stress developed in screws, implant and bony parts differed significantly between volar and dorsal plate conditions. The displacement of implant and bony parts in volar plating was more than dorsal plating (p=0.05). However, the screws displacement in dorsal plating significantly increased compared to volar plating. Conclusion: The stress developed in dorsal and volar implants is not too high to fail the structure. However, it seems that the irritation of soft tissue and tendon would be less in volar inserted implant than dorsal implant. It is recommended to use valor plating to be a good approach for stabilizing the distal part fracture of radius

An Observational Cohort of First Episode Psychosis in Iran:The Azeri Recent Onset Acute Phase Psychosis Survey (ARAS Cohort) Study Protocol

Background: Most of our knowledge about the etiology, course, treatment, and outcome of schizophrenia spectrum and other psychotic disorders stems from Western countries. Data from populations living in other geographical areas and low- and middle-income countries, with different genomes (ethnicity) and exposomes (e.g., culture and social support, drugs of abuse, religion), will add to our knowledge of this complex disorder. Methods: The Azeri Acute phase/Recent onset psychosis Survey (ARAS) has been initiated to study the course of the disorder in patients with recent-onset psychosis using validated diagnostic tools and a comprehensive outcome monitoring system, aiming to reveal indicators for understanding the risk and resilience factors and for choosing the best-personalized treatment strategy. All participants will be evaluated for clinical signs and symptoms as well as risk and resilience factors and will be followed up for 1, 3, and 5 years for outcomes in several domains. A hierarchical cluster method will be applied to identify the number of clusters for each outcome. Defined models will be applied to assess the predictive value of cognition on symptomatic and functional outcomes at follow-up. Discussion: The ARAS cohort will yield significant academic- (research and education) and care-related achievements. ARAS data and experience will have value both in being a useful model for other parts of this region and in an expansion of the currently available knowledge

Screening role of complete blood cell count indices and C reactive protein in patients who are symptomatic for COVID-19

INTRODUCTION: Diagnosis of COVID-19 is through polymerase chain reaction (PCR) or typical involvement of the lung by the virus in computed tomography (CT) scan. However, PCR is not always available, and also CT scan has a high dose of radiation. This study was performed to find the role of complete blood cell (CBC) indices and qualitative C-reactive protein (CRP) in screening of symptomatic patients.MATERIAL AND METHODS: A diagnostic accuracy study was performed on symptomatic cases in Abadan. Four stepwise logistic regression models were designed that the outcomes were PCR positivity, CT scan positivity, PCR and CT scan positivity, and COVID-19 positivity (i.e., PCR or CT scan positivity). Post-estimation receiver operating characteristics (ROC) curve analysis was performed to report the area under the curve (AUC).RESULTS: A total of 104 patients were studied. The most accurate model was for the prediction of CT scan positivity (AUC = 0.874) in which the predictors were age [odds ratio (OR) =1.063] and CRP (OR = 2.661 for each plus of positivity). The second accurate model was for the prediction of COVID-19 positivity (AUC = 0.828) in which the predictors were white blood cell count (OR = 0.735 for every 1000 counts per μL) and neutrophil per lymphocyte ratio (OR = 1.248).CONCLUSIONS: Higher levels of CRP are associated with and predictor of lung involvement in COVID-19 infection. CRP qualitative levels can be measured before a CT scan if there is no other indication for imaging

Integrin-mediated interactions control macrophage polarization in 3D hydrogels

Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment towards inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, we demonstrated that macrophage polarity within biomaterials can be controlled through integrin mediated interactions between human monocytic THP-1 cells and collagen-derived matrix. Surface marker, gene expression, biochemical and cytokine profiling consistently indicated that THP-1 cells within a biomaterial lacking cell attachment motifs yielded pro-inflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of IL-4 induced an anti-inflammatory M2 like phenotype and propagated the effect of IL-4 in induction of M2 like macrophages. Importantly, integrin α2β1 played a pivotal role as its inhibition blocked the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity was further confirmed by its ability to modulate the effect of IL-4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, our study represents a novel, versatile and effective strategy to steer macrophage polarity through integrin mediated three-dimensional (3D) microenvironment for biomaterial-based programming. This development has wide implications for controlling inflammation, angiogenesis, cell proliferation, and tissue regeneration for a myriad of applications including tissue engineered implants, drug delivery vehicles, and implantable devices

LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer- encapsulated methotrexate

Methotrexate (MTX) is a folate analogue antimetabolite widely used for the treatment of rheumatoid arthritis and cancer. A number of studies have shown that MTX delivered via nanoparticle carriers is more potent against cancer cells than free MTX, a phenomenon attributed to higher cellular uptake of the particles compared to the saturable folate receptor pathway. In this study, a cell-based global metabolic profiling approach was applied to study the effects of MTX in both free drug form and when encapsulated in-poly(lactide-co-glycolide) (PLGA) nanoparticles on a cancer cell line, A549, and also on human-like THP-1 macrophages. The results showed that MTX loaded nanoparticles had less impact on the macrophages than free MTX, and the effects on macrophages were limited to changes in nucleotide metabolism and suppression of the tricarboxylic acid cycle, whereas free MTX also led to a drop in glycolytic activity and impairment in redox homeostasis. In contrast, MTX loaded nanoparticles showed a greater impact on A549 cells than the free drug, which was in accord with studies in other cell lines in prior literature with MTX-carrier nanoparticles