The effect of fibrinogen concentrate and fresh frozen plasma on the outcome of patients with acute traumatic coagulopathy: A quasi-experimental study.

INTRODUCTION: The debate on replacing coagulation factors and its effect on the final outcome of the patients with acute traumatic coagulopathy (ATC) in need of transfusion is still ongoing. Therefore, the present study is designed with the aim of comparing the outcome of patients with acute traumatic coagulopathies receiving fibrinogen and fresh frozen plasma (FFP). METHODS: In this quasi-experimental randomized controlled study, patients with severe blunt trauma (ISS>16) and in need of packed cells transfusion were divided into 3 groups of receiving fibrinogen, receiving FFP, and control, and their final outcome was compared. RESULTS: 90 patients with the mean age of 33.16±16.32years were randomly allocated to one of the 3 study groups (82.2% male). The 3 groups were similar regarding baseline characteristics. Patients receiving fibrinogen needed significantly less packed cells (p=0.044) and intravenous fluid in the initial 24h of hospitalization (p=0.022). In addition, mortality rate (p=0.029), need for admission to intensive care unit (p=0.020) and duration of hospitalization (p=0.045) were also lower in the group receiving fibrinogen. The number of sepsis cases in patients receiving fibrinogen and control group was lower than those who received FFP (p=0.001). The number of multiple organ failure cases in patients receiving fibrinogen was about one fourth of the other 2 groups (p=0.106), and a fewer number of them needed mechanical ventilation (p=0.191). No case of venous thrombosis was detected in any of the 3 groups. CONCLUSION: Multiple trauma patients in need of transfusion who received fibrinogen along with packed cells had significantly better outcomes regarding mortality, sepsis, need for admission to the intensive care unit, need for receiving packed cells, need for receiving intravenous fluids in the initial 24h, and duration of hospitalization.

Microfluidic approaches to the study of angiogenesis and the microcirculation.

Microfluidic systems have emerged as a new class of perfusable in vitro culture models that have helped advance and refine our understanding of microvascular function. Cutting-edge microfluidic models have successfully integrated principles from quantitative analysis of vascular function, in vitro flow chambers, microfabrication techniques, and 3D tissue scaffolds. Here, we review the evolution of microfluidic systems, namely their progression from 2D planar microchannel arrays to 3D microtissue analogs, and highlight their recent contributions in elucidating the role of biomolecular transport and fluid mechanical stimuli in controlling angiogenesis. Further advancement of microfluidic systems in recapitulating tissue-level phenomena in vitro, controlling important physiochemical and biological parameters, and integrating cellular and molecular analysis will help further enhance their application within the microcirculation research community.

Comparison of platelet number and function between nonalcoholic fatty liver disease and normal individuals.

BACKGROUND: There is interest about the role of platelet (PLT) number and function in nonalcoholic fatty liver disease (NAFLD). NAFLD patients have abnormalities of PLT number and function, especially mean platelet volume (MPV) which is known as a novel biomarker for atherosclerosis. We decided to compare PLT number and function between NAFLD and healthy participants. MATERIALS AND METHODS: In this case-control study, two groups of patients (65 cases with NAFLD and 65 cases without NAFLD) were included consecutively. The diagnosis of NAFLD was made using ultrasound examination of the liver. Venous blood samples were taken, and the required laboratory markers including PLT number and function (MPV, platelet distribution width [PDW]), prothrombin time (PT), partial thromboplastin time (PTT), lipid profile, hepatic transaminases, ferritin, and fasting blood sugar were assayed. RESULTS: Mean (± standard deviation [SD]) MPV in NAFLD group (10.29 ± 0.95 fL) was significantly higher than in control group (9.56 ± 1.18 fL); P < 0.001. No significant difference was observed regarding mean (± SD) PLT count between NAFLD (271.20 ± 52.11 × 103/mm3) and healthy participants (262.86 ± 75.81 × 103/mm3) (P = 0.46). Mean (± SD) PDW values were not significantly different between NAFLD and control groups. Logistic regression showed that NAFLD was positively associated with higher MPV (odds ratio [OR] =1.9, 95% confidence interval [CI] =1.20-3.02) and body mass index (OR = 1.5, 95% CI = 1.05-2.15) values. However, PT (OR = 0.14, 95% CI = 0.02-0.82) and PTT (OR = 0.72, 95% CI = 0.58-0.88) had negative association with NAFLD. CONCLUSION: Higher MPV was found to be significantly associated with NAFLD. However, such significant association was not detected regarding PLT count or PDW. As MPV is a reported risk factor for atherosclerosis, this marker may be useful in follow-up of patients with NAFLD. These findings provide basis for further studies to address this marker in long-term follow-up of NAFLD patients.

Multi-functional voltage and current based enhancement of power quality in grid-connected microgrids considering harmonics.

The introduction of a renewable energy source (RES) based multi-functional grid-tied inverter (MFGTI) stands as a favorable remedy for addressing power quality concerns within distributed generation (DG) systems and microgrids. Nonetheless, the effectiveness of a traditional MFGTI will be restricted in addressing power quality issues based on voltage. The presented research proposes a novel structure for MFGTI to enhance power quality concerns associated with voltage, current, and harmonic distortions resulting from both grid and loads. Based on this strategy, the introduced MFGTI can be linked with the grid by bidirectional switches either in a parallel or series. This feature provides various operational conditions in response to diverse disruptions in the grid. To effectively adjust the voltage, current and voltage reduction are determined through mathematical analysis, considering both the grid conditions and the load requirements. Furthermore, this strategy offers different compensation strategies, control schemes, and transition modes in the MFGTI. The major disturbances such as unbalanced and balanced voltage swell/sag, harmonics, and interruption are compensated. The shunt compensation controller is based on a second order sequence filter (SOSF) to provide the load current active component. A damping PI regulator based series compensation controller is presented for the voltage swell/sag reduction. Moreover, a new three level hierarchical control is proposed in which a droop control for compensating the interruption and a decouple dual synchronous reference frame (DDSRF) for compensating the unbalanced voltage sag/swell are utilized. The simulations in the MATLAB/SIMULINK show that using the proposed compensation strategies, the proposed MFGTI can compensate effectively the different disturbances through changing the transition states by the proposed algorithm based bidirectional switches.

Multi-objective economic operation of smart distribution network with renewable-flexible virtual power plants considering voltage security index.

This paper discusses the simultaneous management of active and reactive power of a flexible renewable energy-based virtual power plant placed in a smart distribution system, based on the economic, operational, and voltage security objectives of the distribution system operator. The formulated problem aims to specify the minimum weighted sum of energy cost, energy loss, and voltage security index, considering the optimal power flow model, voltage security formulation, and the operating model of the virtual power plant. The virtual unit includes renewable sources, like wind systems, photovoltaic, and bio-waste units. Flexibility resources include electric vehicle parking lot and price-based demand response. In the mentioned scheme, parameters of load, renewable sources, electric vehicles, and energy prices are uncertain. This paper utilizes the Unscented Transformation method for modeling uncertainties. Fuzzy decision-making is utilized to extract a compromised solution. The suggested approach innovatively considers the simultaneous management of active and reactive power of a virtual unit with electric vehicles and price-based demand response. This is performed to promote economic, operational, and network security objectives. According to numerical results, the approach with optimal power management of renewable virtual units is capable of boosting the economic, operation, and voltage security status of the network by approximately 43%, 47-62%, and 26.9%, respectively, to power flow studies. Only price-based demand response can improve the voltage security, operation, and economic states of the network by about 19.5%, 35-47%, and 44%, respectively, compared to the power flow model.

SqueezeNet for the forecasting of the energy demand using a combined version of the sewing training-based optimization algorithm.

With the introduction of various loads and dispersed production units to the system in recent years, the significance of precise forecasting for short, long, and medium loads have already been recognized. It is important to analyze the power system's performance in real-time and the appropriate response to changes in the electric load to make the best use of energy systems. Electric load forecasting for a long period in the time domain enables energy producers to increase grid stability, reduce equipment failures and production unit outages, and guarantee the dependability of electricity output. In this study, SqueezeNet is first used to obtain the required power demand forecast at the user end. The structure of the SqueezeNet is then enhanced using a customized version of the Sewing Training-Based Optimizer. A comparison between the results of the suggested method and those of some other published techniques is then implemented after the method has been applied to a typical case study with three different types of demands-short, long, and medium-term. A time window has been set up to collect the objective and input data from the customer at intervals of 20 min, allowing for highly effective neural network training. The results showed that the proposed method with 0.48, 0.49, and 0.53 MSE for Forecasting the short-term, medium-term, and long-term electricity provided the best results with the highest accuracy. The outcomes show that employing the suggested technique is a viable option for energy consumption forecasting.

Engineering Nano/Microscale Chiral Self-Assembly in 3D Printed Constructs.

Helical hierarchy found in biomolecules like cellulose, chitin, and collagen underpins the remarkable mechanical strength and vibrant colors observed in living organisms. This study advances the integration of helical/chiral assembly and 3D printing technology, providing precise spatial control over chiral nano/microstructures of rod-shaped colloidal nanoparticles in intricate geometries. We designed reactive chiral inks based on cellulose nanocrystal (CNC) suspensions and acrylamide monomers, enabling the chiral assembly at nano/microscale, beyond the resolution seen in printed materials. We employed a range of complementary techniques including Orthogonal Superposition rheometry and in situ rheo-optic measurements under steady shear rate conditions. These techniques help us to understand the nature of the nonlinear flow behavior of the chiral inks, and directly probe the flow-induced microstructural dynamics and phase transitions at constant shear rates, as well as their post-flow relaxation. Furthermore, we analyzed the photo-curing process to identify key parameters affecting gelation kinetics and structural integrity of the printed object within the supporting bath. These insights into the interplay between the chiral inks self-assembly dynamics, 3D printing flow kinematics and photo-polymerization kinetics provide a roadmap to direct the out-of-equilibrium arrangement of CNC particles in the 3D printed filaments, ranging from uniform nematic to 3D concentric chiral structures with controlled pitch length, as well as random orientation of chiral domains. Our biomimetic approach can pave the way for the creation of materials with superior mechanical properties or programable photonic responses that arise from 3D nano/microstructure and can be translated into larger scale 3D printed designs.

Low cost and massively parallel force spectroscopy with fluid loading on a chip.

Current approaches for single molecule force spectroscopy are typically constrained by low throughput and high instrumentation cost. Herein, a low-cost, high throughput technique is demonstrated using microfluidics for multiplexed mechanical manipulation of up to ~4000 individual molecules via molecular fluid loading on-a-chip (FLO-Chip). The FLO-Chip consists of serially connected microchannels with varying width, allowing for simultaneous testing at multiple loading rates. Molecular force measurements are demonstrated by dissociating Biotin-Streptavidin and Digoxigenin-AntiDigoxigenin interactions along with unzipping of double stranded DNA of varying sequence under different dynamic loading rates and solution conditions. Rupture force results under varying loading rates and solution conditions are in good agreement with prior studies, verifying a versatile approach for single molecule biophysics and molecular mechanobiology. FLO-Chip enables straightforward, rapid, low-cost, and portable mechanical testing of single molecules that can be implemented on a wide range of microscopes to broaden access and may enable new applications of molecular force spectroscopy.

Multiplexed Detection of Molecular Interactions with DNA Origami Engineered Cells in 3D Collagen Matrices.

The interactions of cells with signaling molecules present in their local microenvironment maintain cell proliferation, differentiation, and spatial organization and mediate progression of diseases such as metabolic disorders and cancer. Real-time monitoring of the interactions between cells and their extracellular ligands in a three-dimensional (3D) microenvironment can inform detection and understanding of cell processes and the development of effective therapeutic agents. DNA origami technology allows for the design and fabrication of biocompatible and 3D functional nanodevices via molecular self-assembly for various applications including molecular sensing. Here, we report a robust method to monitor live cell interactions with molecules in their surrounding environment in a 3D tissue model using a microfluidic device. We used a DNA origami cell sensing platform (CSP) to detect two specific nucleic acid sequences on the membrane of B cells and dendritic cells. We further demonstrated real-time detection of biomolecules with the DNA sensing platform on the surface of dendritic cells in a 3D microfluidic tissue model. Our results establish the integration of live cells with membranes engineered with DNA nanodevices into microfluidic chips as a highly capable biosensor approach to investigate subcellular interactions in physiologically relevant 3D environments under controlled biomolecular transport.

Endothelial barrier function is co-regulated at vessel bifurcations by fluid forces and sphingosine-1-phosphate.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry generates hemodynamic forces at the bifurcation point distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which is characterized by approximately zero shear stress and 38 dyn•cm-2 stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of S1P with 3 dyn•cm-2 laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to bifurcated fluid flow and laminar shear stress is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.

Direct current electric field regulates endothelial permeability under physiologically relevant fluid forces in a microfluidic vessel bifurcation model.

Previous in vitro studies have reported on the use of direct current electric fields (DC-EFs) to regulate vascular endothelial permeability, which is important for tissue regeneration and wound healing. However, these studies have primarily used static 2D culture models that lack the fluid mechanical forces associated with blood flow experienced by endothelial cells (ECs) in vivo. Hence, the effect of DC-EF on ECs under physiologically relevant fluid forces is yet to be systematically evaluated. Using a 3D microfluidic model of a bifurcating vessel, we report the role of DC-EF on regulating endothelial permeability when co-applied with physiologically relevant fluid forces that arise at the vessel bifurcation. The application of a 70 V m-1 DC-EF simultaneously with 1 µL min-1 low perfusion rate (generating 3.8 dyn cm-2 stagnation pressure at the bifurcation point and 0.3 dyn cm-2 laminar shear stress in the branched vessel) increased the endothelial permeability 7-fold compared to the static control condition (i.e., without flow and DC-EF). When the perfusion rate was increased to 10 µL min-1 (generating 38 dyn cm-2 stagnation pressure at the bifurcation point and 3 dyn cm-2 laminar shear stress in the branched vessel) while maintaining the same electrical stimulation, a 4-fold increase in endothelial permeability compared to the static control was observed. The lower increase in endothelial permeability for the higher fluid forces but the same DC-EF suggests a competing role between fluid forces and the applied DC-EF. Moreover, the observed increase in endothelial permeability due to combined DC-EF and flow was transient and dependent on the Akt signalling pathway. Collectively, these findings provide significant new insights into how the endothelium serves as an electro-mechanical interface for regulating vessel permeability.

Relevance between Helicobacter pylori Infection and Non-Alcoholic Fatty Liver Disease in Birjand, Iran.

There is evidence that infection by H. pylori can have a critical proportion in the development of hepatocyte injury and both noncancerous and malignant liver conditions including non-alcoholic fatty liver disease (NAFLD). This is attributed to several mechanisms, the most important one being the toxic products of the bacterium H. pylori and oxidative injury for hepatocytes which promotes hepatic injury. The present research was aimed at determining the association between H. pylori infection and the prevalence of NAFLD in Birjand, Iran. Two groups were included in this cross-sectional study at the outpatient university clinic. One group had NAFLD (65 patients) and the other group was healthy controls without NAFLD (65 subjects). The diagnosis of NAFLD was performed using abdominal ultrasound examination and the absence of taking steatogenic medications or alcohol. Serum anti-H. pylori IgG and fecal H. pylori antigen were tested for diagnosing of H. pylori infection using ELISA method. H. pylori infection diagnosis was made if both tests were positive. None of the subjects in either group had symptoms related to the digestive system including dyspepsia, GERD (gastroesophageal reflux disease), or epigastric pain suspicious of peptic ulcer disease. There were 37 patients (28.5%) in both NAFLD (22 cases, 33.8%) and control (15 cases, 23.1%) groups whose H. pylori tests (both IgG and fecal antigen) were positive. Statistically, no significant difference was observed between the two studied groups regarding H. pylori infection frequency (p = 0.37). Asymptomatic H. pylori infection rate was not significantly different between NAFLD patients and control subjects in Birjand, Iran.

Kinetics of temperature effect on antioxidant activity, phenolic compounds and color of Iranian jujube honey.

In the present study, the Iranian jujube honey was evaluated for its total antioxidant activity by DPPH assay, total phenolic content (TPC) by using the Folin-Ciocalteu reagent, and brown pigment formation (BPF). The kinetics of changes in jujube honey samples heated at various temperatures (45, 55 and 65 °C) over 10 days were studied. Increasing treatment temperature and time caused an increase in all three parameters including, antioxidant activity, BPF and TPC. Increases in BPF and TPC followed zero-order kinetics, and the rise in antioxidant activity varied depending on heating temperatures, following second-order, first-order and zero-order kinetics when samples were heated at 45, 55 and 65 °C, respectively. At 45-65 °C, activation energy values of 68 and 64.7 kJ/mol-1 were obtained for BPF and TPC, respectively. Linear relationships were observed between antioxidant activity and BPF, TPC and antioxidant activity, and BPF and TPC, such that the highest phenol content was related to the darkest honey sample. For all three parameters, heating honey to 65 °C was found to be more effective than heating to 45 or 55 °C.

Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model.

Sprouting angiogenesis-the infiltration and extension of endothelial cells from pre-existing blood vessels-helps orchestrate vascular growth and remodeling. It is now agreed that fluid forces, such as laminar shear stress due to unidirectional flow in straight vessel segments, are important regulators of angiogenesis. However, regulation of angiogenesis by the different flow dynamics that arise due to vessel branching, such as impinging flow stagnation at the base of a bifurcating vessel, are not well understood. Here we used a recently developed 3-D microfluidic model to investigate the role of the flow conditions that occur due to vessel bifurcations on endothelial sprouting. We observed that bifurcating fluid flow located at the vessel bifurcation point suppresses the formation of angiogenic sprouts. Similarly, laminar shear stress at a magnitude of ~3 dyn/cm2 applied in the branched vessels downstream of the bifurcation point, inhibited the formation of angiogenic sprouts. In contrast, co-application of ~1 µm/s average transvascular flow across the endothelial monolayer with laminar shear stress induced the formation of angiogenic sprouts. These results suggest that transvascular flow imparts a competing effect against bifurcating fluid flow and laminar shear stress in regulating endothelial sprouting. To our knowledge, these findings are the first report on the stabilizing role of bifurcating fluid flow on endothelial sprouting. These results also demonstrate the importance of local flow dynamics due to branched vessel geometry in determining the location of sprouting angiogenesis.

Flow dynamics control endothelial permeability in a microfluidic vessel bifurcation model.

Endothelial barrier function is known to be regulated by a number of molecular mechanisms; however, the role of biomechanical signals associated with blood flow is comparatively less explored. Biomimetic microfluidic models comprised of vessel analogues that are lined with endothelial cells (ECs) have been developed to help answer several fundamental questions in endothelial mechanobiology. However, previously described microfluidic models have been primarily restricted to single straight or two parallel vessel analogues, which do not model the bifurcating vessel networks typically present in physiology. Therefore, the effects of hemodynamic stresses that arise due to bifurcating vessel geometries on ECs are not well understood. Here, we introduce and characterize a microfluidic model that mimics both the flow conditions and the endothelial/extracellular matrix (ECM) architecture of bifurcating blood vessels to systematically monitor changes in endothelial permeability mediated by the local flow dynamics at specific locations along the bifurcating vessel structure. We show that bifurcated fluid flow (BFF) that arises only at the base of a vessel bifurcation and is characterized by stagnation pressure of ∼38 dyn cm-2 and approximately zero shear stress induces significant decrease in EC permeability compared to the static control condition in a nitric oxide (NO)-dependent manner. Similarly, intravascular laminar shear stress (LSS) (3 dyn cm-2) oriented tangential to ECs located downstream of the vessel bifurcation also causes a significant decrease in permeability compared to the static control condition via the NO pathway. In contrast, co-application of transvascular flow (TVF) (∼1 µm s-1) with BFF and LSS rescues vessel permeability to the level of the static control condition, which suggests that TVF has a competing role against the stabilization effects of BFF and LSS. These findings introduce BFF at the base of vessel bifurcations as an important regulator of vessel permeability and suggest a mechanism by which local flow dynamics control vascular function in vivo.

Effect of Local N-acetyl-cysteine in the Prevention of Epidural Fibrosis in Rat Laminectomy Model.

BACKGROUND: Epidural fibrosis is a major contributing factor to the onset of failed back syndrome. Many studies have attempted to prevent this physiological response. Interestingly, N-acetyl-cysteine (NAC) has been effective in some cases in the treatment of pulmonary fibrosis. OBJECTIVE: The objective of this study was to determine whether local NAC is an effective way to prevent epidural fibrosis after laminectomy in rats. MATERIALS AND METHODS: Twenty Wistar rats were used in this study. Animals were divided into two groups: NAC group and a control group. We performed two-level laminectomy (L4-L5) in these rats. Rats in the control group just had laminectomy, and in the other group, L4 and L5 laminectomy followed by local treatment with NAC. Four weeks later, the rats were killed, and the laminectomy level was subjected to histopathological examination to evaluate epidural fibrosis and fibroblast density. RESULTS: Histopathological examination showed that after 4 weeks of surgery the NAC group had significantly less epidural fibrosis and fibroblasts compared with control group. CONCLUSION: Our findings indicate that NAC decreased spinal epidural fibrosis after laminectomy in rats.

Engineering Cell Surface Function with DNA Origami.

A specific and reversible method is reported to engineer cell-membrane function by embedding DNA-origami nanodevices onto the cell surface. Robust membrane functionalization across epithelial, mesenchymal, and nonadherent immune cells is achieved with DNA nanoplatforms that enable functions including the construction of higher-order DNA assemblies at the cell surface and programed cell-cell adhesion between homotypic and heterotypic cells via sequence-specific DNA hybridization. It is anticipated that integration of DNA-origami nanodevices can transform the cell membrane into an engineered material that can mimic, manipulate, and measure biophysical and biochemical function within the plasma membrane of living cells.

Concurrent chemoradiation with weekly gemcitabine and cisplatin for locally advanced cervical cancer.

BACKGROUND: For more than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultaneously with radiation. MATERIALS AND METHODS: Thirty women with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in the Radiation Oncology Department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty mg/m2 gemcitabine followed by 35 mg/m(2) cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks. One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment. RESULTS: The mean age of patients was 58.1 ± 11.8 (29-78) years. After 3 months of treatment, 73.3%had complete and 26.7% demonstrated partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients. CONCLUSIONS: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation using Gemcitabine for advanced cervical cancers.