Activation of Endothelial Cells by Antiphospholipid Antibodies—A Possible Mechanism Triggering Thrombosis in Patients with Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. The presence of serum antibodies are collectively termed as antiphospholipid antibodies (aPL) and is the hallmark of the disease. Interest in the pathogenesis has mostly been focused on the blood coagulation factor. However, endothelial cells might play an important role. When stimulated, cell membrane would flip to expose negatively charged phospholipids and activation markers such as adhesive molecules may appear. We consider that these changes may play an important role in the initiation of the thrombotic process when endothelial cells encounter aPL. In this study, we incubated human umbilical vein endothelial cells (HUVECs) with IgG isolated from patients with APS and found that the HUVECs were activated by the expression of negatively charged phospholipids, as shown by high annexin V binding and negative propidium iodide staining and by an increase in the level of intracellular cell adhesion molecule-1 on the cell surface. The above findings indicate that endothelial cells can be activated on exposure to aPL and trigger the thrombotic event

Disseminated peritoneal tuberculosis simulating advanced ovarian cancer: A retrospective study of 17 cases

AbstractObjectivesThe abdominopelvic cavity is one of the common sites for extrapulmonary tubercular infections. The rate of preoperative misdiagnoses between peritoneal tuberculosis (TB) and ovarian cancer is high because of overlapping nonspecific signs and symptoms. We attempted to analyze the experience within our hospital so as to establish the best means of discriminating between peritoneal TB and advanced ovarian cancer.MethodsSeventeen patients diagnosed as having peritoneal TB between July 1986 and December 2008 at the Obstetrics and Gynecology Department of our hospital with the initial presentation simulating advanced ovarian cancer were retrospectively reviewed and evaluated.ResultsPatients’ ages ranged from 24 years to 87 years (median, 38 years). Ten of 17 patients (60%) were younger than 40 years. All patients except one had elevated serum cancer antigen-125 levels with a mean of 358.8U/mL (range, 12–733U/mL). Computed tomographic (CT) scans showed ascites with mesenteric or omental stranding in all (100%), enlarged retroperitoneal lymph nodes in six (35.3%), and an adnexal mass in three (17.6%). Abdominal paracentesis was performed in seven cases, in which the findings revealed lymphocyte-dominant ascites without malignant cells. Surgical intervention by laparotomy was performed in 13 cases (76%) and by laparoscopy in three cases (18%), and a CT-guided peritoneal biopsy was performed in one case (6%). A frozen section was taken from 16 patients but not the patient who received a CT-guided peritoneal biopsy, and all revealed granulomatous inflammation. A final pathological examination confirmed a diagnosis of peritoneal TB. All patients responded to anti-TB treatment.ConclusionsIn view of these data, a clinical diagnosis of peritoneal TB should be considered in a relatively young female with nonspecific symptoms of abdominal distension and wasting, as well as lymphocytic ascites without malignant cells. Laparoscopy or a minilaparotomy to obtain tissue samples for frozen-section analysis may be the most direct and least-invasive approach for a diagnosis, thus avoiding unnecessary extended surgery in these patients

Effect of Top-Region Area of Flat-Top Pyramid Patterned Sapphire Substrate on the Optoelectronic Performance of GaN-Based Light-Emitting Diodes

The flat-top pyramid patterned sapphire substrates (FTP-PSSs) have been prepared for the growth of GaN epilayers and the fabrication of lateral-type light-emitting diodes (LEDs) with an emission wavelength of approximately 470 nm. Three kinds of FTP-PSSs, which were denoted as FTP-PSS-A, FTP-PSS-B, and FTP-PSS-C, respectively, were formed through the sequential wet etching processes. The diameters of circle areas on the top regions of these three FTP-PSSs were 1, 2, and 3 μm, respectively. Based on the X-ray diffraction results, the full-width at half-maximum values of rocking curves at (002) plane for the GaN epilayers grown on conventional sapphire substrate (CSS), FTP-PSS-A, FTP-PSS-B, and FTP-PSS-C were 412, 238, 346, and 357 arcsec, while these values at (102) plane were 593, 327, 352, and 372 arcsec, respectively. The SpeCLED-Ratro simulation results reveal that the LED prepared on FTP-PSS-A has the highest light extraction efficiency than that of the other devices. At an injection current of 350 mA, the output powers of LEDs fabricated on CSS, FTP-PSS-A, FTP-PSS-B, and FTP-PSS-C were 157, 254, 241, and 233 mW, respectively. The results indicate that both the crystal quality of GaN epilayer and the light extraction of LED can be improved via the use of FTP-PSS, especially for the FTP-PSS-A

Anapole mediated giant photothermal nonlinearity in nanostructured silicon

Featured with a plethora of electric and magnetic Mie resonances, high index dielectric nanostructures offer a versatile platform to concentrate light-matter interactions at the nanoscale. By integrating unique features of far-field scattering control and near-field concentration from radiationless anapole states, here, we demonstrate a giant photothermal nonlinearity in single subwavelength-sized silicon nanodisks. The nanoscale energy concentration and consequent near-field enhancements mediated by the anapole mode yield a reversible nonlinear scattering with a large modulation depth and a broad dynamic range, unveiling a record-high nonlinear index change up to 0.5 at mild incident light intensities on the order of MW/cm2. The observed photothermal nonlinearity showcases three orders of magnitude enhancement compared with that of unstructured bulk silicon, as well as nearly one order of magnitude higher than that through the radiative electric dipolar mode. Such nonlinear scattering can empower distinctive point spread functions in confocal reflectance imaging, offering the potential for far-field localization of nanostructured Si with an accuracy approaching 40 nm. Our findings shed new light on active silicon photonics based on optical anapoles

Pretreatment carcinoembryonic antigen level is a risk factor for para-aortic lymph node recurrence in addition to squamous cell carcinoma antigen following definitive concurrent chemoradiotherapy for squamous cell carcinoma of the uterine cervix

<p>Abstract</p> <p>Background</p> <p>To identify pretreatment carcinoembryonic antigen (CEA) levels as a risk factor for para-aortic lymph node (PALN) recurrence following concurrent chemoradiotherapy (CCRT) for cervical cancer.</p> <p>Methods</p> <p>From March 1995 to January 2008, 188 patients with squamous cell carcinoma (SCC) of the uterine cervix were analyzed retrospectively. No patient received PALN irradiation as the initial treatment. CEA and squamous cell carcinoma antigen (SCC-Ag) were measured before and after radiotherapy. PALN recurrence was detected by computer tomography (CT) scans. We analyzed the actuarial rates of PALN recurrence by using Kaplan-Meier curves. Multivariate analyses were carried out with Cox regression models. We stratified the risk groups based on the hazard ratios (HR).</p> <p>Results</p> <p>Both pretreatment CEA levels ≥ 10 ng/mL and SCC-Ag levels < 10 ng/mL (<it>p </it>< 0.001, HR = 8.838), SCC-Ag levels ≥ 40 ng/mL (<it>p </it>< 0.001, HR = 12.551), and SCC-Ag levels of 10-40 ng/mL (<it>p </it>< 0.001, HR = 4.2464) were significant factors for PALN recurrence. The corresponding 5-year PALN recurrence rates were 51.5%, 84.8%, and 27.5%, respectively. The 5-year PALN recurrence rate for patients with both low (< 10 ng/mL) SCC and CEA was only 9.6%. CEA levels ≥ 10 ng/mL or SCC-Ag levels ≥ 10 ng/mL at PALN recurrence were associated with overall survival after an isolated PALN recurrence. Pretreatment CEA levels ≥ 10 ng/mL were also associated with survival after an isolated PALN recurrence.</p> <p>Conclusions</p> <p>Pretreatment CEA ≥ 10 ng/mL is an additional risk factor of PALN relapse following definitive CCRT for SCC of the uterine cervix in patients with pretreatment SCC-Ag levels < 10 ng/mL. More comprehensive examinations before CCRT and intensive follow-up schedules are suggested for early detection and salvage in patients with SCC-Ag or CEA levels ≥ 10 ng/mL.</p

Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects

BackgroundOrganophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years.ObjectivesInvestigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population.MethodsDifferent age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined.ResultsThe mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 μg/L (standard deviation (SD) of 1.91 μg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 μg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p&lt;0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns.ConclusionTo our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships

Combinatorial Polymer Electrospun Matrices Promote Physiologically-Relevant Cardiomyogenic Stem Cell Differentiation

Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs) towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG), hydrophobic poly(ε-caprolactone) (PCL), and negatively-charged, carboxylated PCL (CPCL). Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS), α-myosin heavy chain expression (α-MHC), and intracellular Ca2+ signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca2+ signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca2+ handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques

Prospects of Nanotechnology in Clinical Immunodiagnostics

Nanostructured materials are promising compounds that offer new opportunities as sensing platforms for the detection of biomolecules. Having micrometer-scale length and nanometer-scale diameters, nanomaterials can be manipulated with current nanofabrication methods, as well as self-assembly techniques, to fabricate nanoscale bio-sensing devices. Nanostructured materials possess extraordinary physical, mechanical, electrical, thermal and multifunctional properties. Such unique properties advocate their use as biomimetic membranes to immobilize and modify biomolecules on the surface of nanoparticles. Alignment, uniform dispersion, selective growth and diameter control are general parameters which play critical roles in the successful integration of nanostructures for the fabrication of bioelectronic sensing devices. In this review, we focus on different types and aspects of nanomaterials, including their synthesis, properties, conjugation with biomolecules and their application in the construction of immunosensing devices. Some key results from each cited article are summarized by relating the concept and mechanism behind each sensor, experimental conditions and the behavior of the sensor under different conditions, etc. The variety of nanomaterial-based bioelectronic devices exhibiting novel functions proves the unique properties of nanomaterials in such sensing devices, which will surely continue to expand in the future. Such nanomaterial based devices are expected to have a major impact in clinical immunodiagnostics, environmental monitoring, security surveillance and for ensuring food safety

Association Between Acid-Sensing Ion Channel 3 Gene Variants and Balance Impairment in People With Mild Traumatic Brain Injury

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown.Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test.Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01).Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe