Application of Targeted Coronary Angiography in the Diagnosis of Sudden Cardiac Death.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS: Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.

Development of a Self-Viscosity and Temperature-Compensated Technique for Highly Stable and Highly Sensitive Bead-Based Diffusometry.

Brownian motion, which is a natural phenomenon, has attracted numerous researchers and received extensive studies over the past decades. The effort contributes to the discovery of optical diffusometry, which is commonly used for micro/nano particle sizing. However, the analysis uncertainty caused by the coupling relationship among particle diameter, temperature, and fluid viscosity usually poses a barrier to precise measurement. Preventing random background noise becomes the key to achieving a high level of accuracy in diffusometry detection. Recently, Janus particles have become known as an ideal tool for resolving the rotational Brownian motion. Followed by our previous study, the rotational Brownian motion and the translational Brownian motion can be separately measured using the Janus particles. Accordingly, a simple self-viscosity and temperature-compensated technique based on the delicate removal of temperature and fluid viscosity variations through particle tracking was first proposed in this study. Consequently, the translational Brownian motion was expressed in terms of particle trajectory, whereas the rotational Brownian motion was expressed in terms of the blinking signal from the Janus particles. The algorithm was verified simulatively and experimentally in temperature (10 °C to 40 °C) and viscosity-controlled (1 mPa·s to 5 mPa·s) fields. In an evaluation of biosensing for a target protein, IFN-γ, the limit of detection of the proposed self-compensated diffusometry reached 0.45 pg/mL, whereas its uncertainties of viscosity and temperature were 96 and 15-fold lower than the pure the rotational Brownian motion counterpart, respectively. The results indicated the low-uncertainty and high-accuracy biosensing capability resulting from the self-viscosity and temperature-compensated technique. This research will provide a potential alternative to future similar bead-based immunosensing, which requires ultra-high stability and sensitivity.

Study on the Strip Warpage Issues Encountered in the Flip-Chip Process.

This study successfully established a strip warpage simulation model of the flip-chip process and investigated the effects of structural design and process (molding, post-mold curing, pretreatment, and ball mounting) on strip warpage. The errors between simulated and experimental values were found to be less than 8%. Taguchi analysis was employed to identify the key factors affecting strip warpage, which were discovered to be die thickness and substrate thickness, followed by mold compound thickness and molding temperature. Although a greater die thickness and mold compound thickness reduce the strip warpage, they also substantially increase the overall strip thickness. To overcome this problem, design criteria are proposed, with the neutral axis of the strip structure located on the bump. The results obtained using the criteria revealed that the strip warpage and overall strip thickness are effectively reduced. In summary, the proposed model can be used to evaluate the effect of structural design and process parameters on strip warpage and can provide strip design guidelines for reducing the amount of strip warpage and meeting the requirements for light, thin, and short chips on the production line. In addition, the proposed guidelines can accelerate the product development cycle and improve product quality with reduced development costs.

Rapid and Sensitive Pathogen Detection by DNA Amplification Using Janus Particle-Enabled Rotational Diffusometry.

Rapid and sensitive detection of infectious bacteria is in all-time high demand to prevent the further spread of the infection and allow early medical intervention. In this study, we use rotational diffusometry (RD), a natural phenomenon characterized by Janus particles, to detect pathogens like Escherichia coli by performing amplification of specific genes. This biosensing method is used to measure the change in viscosity of the fluid in the presence and absence of DNA in the solution by capturing images of modified microbeads at 10 Hz by a CCD camera followed by cross-correlation algorithm analysis. Using rotational diffusometry, we have achieved E. coli detection with 50 pg/µL DNA with a measurement time of 30 s and a sample volume of 2 µL. This sensitivity was achieved with 30 thermal cycles for three different amplicons, viz., 84, 147, and 246 bp. Meanwhile, in the case of 10 and 20 thermal cycles, the detection sensitivity was achieved with 0.1 and 1 ng/µL DNA concentrations for a 246 bp amplicon. Compared with conventional PCR, this technique appears to improve the detection time, thereby reaching a turnaround time of less than 60 min. Other studies showed a successful identification of DNA amplification up to 10 thermal cycles with different sizes of amplicons. The effect of DNA concentration, amplicon size, and the number of thermal cycles on the detection of E. coli was examined in detail and represented in the form of three maps. These maps show the clear difference and the advantages of RD method in comparison with conventional PCR. This unconventional and rapid biosensing method can be used further for downstream application of nucleic acid amplification-based pathogen detection and early disease control.

Caenorhabditis elegans exhibits positive gravitaxis.

BACKGROUND: Gravity plays an important role in most life forms on Earth. Yet, a complete molecular understanding of sensing and responding to gravity is lacking. While there are anatomical differences among animals, there is a remarkable conservation across phylogeny at the molecular level. Caenorhabditis elegans is suitable for gene discovery approaches that may help identify molecular mechanisms of gravity sensing. It is unknown whether C. elegans can sense the direction of gravity. RESULTS: In aqueous solutions, motile C. elegans nematodes align their swimming direction with the gravity vector direction while immobile worms do not. The worms orient downward regardless of whether they are suspended in a solution less dense (downward sedimentation) or denser (upward sedimentation) than themselves. Gravitaxis is minimally affected by the animals' gait but requires sensory cilia and dopamine neurotransmission, as well as motility; it does not require genes that function in the body touch response. CONCLUSIONS: Gravitaxis is not mediated by passive forces such as non-uniform mass distribution or hydrodynamic effects. Rather, it is mediated by active neural processes that involve sensory cilia and dopamine. C. elegans provides a genetically tractable system to study molecular and neural mechanisms of gravity sensing.

Facile open-well immunofluorescence enhancement with coplanar-electrodes-enabled optoelectrokinetics and magnetic particles.

Electrokinetic manipulation has been proven powerful in enhancing the sensing capability of general-purpose biochips. However, the close-form configuration of biochips and the required use of low electric conductivity limit their practicability. In this study, an open-well microfluidic system facilitated with coplanar-electrodes-enabled optoelectrokinetic concentration and magnetic particles were therefore developed to overcome these challenges. The open side achieves optoelectrokinetic manipulation for biosignal enhancement, enabling free manual operations. Magnetic particles were employed in immunoassays to facilitate the rapid onsite separation of targets. A common cytokine biomarker found in many diseases, that is, tumor necrosis factor alpha (TNF-α), was used for assessing the immunosensing system. In addition to the benefits inherited from the immunoassays, the fluorescent signal enhanced by the optoelectrokinetic technique also featured rapid enhancement in 1 min and a limit of detection of as low as 2.9 pg/mL. The open-well architecture allowed the entire immunosensing process to be completed on site without frequent off-site washing. For a practical test, the TNF-α in human tear fluids was measured by the developed device and validated with a standard enzyme-linked immunosorbent assay (ELISA). The data show consistency in terms of trend. The developed open-well optoelectrokinetic device provides an insight into future facile clinical diagnoses. By simply modifying the surface linkers on the magnetic particles, the technique can be further extended to more other trace biomarker detections.

Multifactor study of efficacy and recurrence in laparoscopic surgery for inguinal hernia.

BACKGROUND: Inguinal hernia is a common clinical manifestation in children with a low self-healing rate. AIM: To determine the effect of laparoscopic surgery on indirect inguinal hernia and the risk factors for postoperative recurrence and to provide a reference for the clinical treatment and prevention of recurrence. METHODS: We selected 360 children who underwent laparoscopic high ligation in our hospital as the laparoscopic group and 120 patients treated for inguinal hernia with conventional surgery as the control group. The operation time, blood loss, incision length, hospitalization time, total hospitalization cost and surgical complications were compared between the two groups. According to telephone follow-up or return visits, the children who had recurrence within 2 years after the operation in the laparoscopic group were analyzed, and the laparoscopic high ligation hernia sac level was analyzed by the logistic multifactor method. Ligation was used to treat recurrence in children with inguinal hernia. RESULTS: The operation time, blood loss, length of incision, and length of hospital stay in the laparoscopic group were lower than those in the control group (P < 0.05). The total hospitalization cost in the laparoscopic group was higher than that in the control group (P < 0.05). The operative complication rate was 1.67% lower than that in the control group (12.50%) (P < 0.05). In 360 children with laparoscopic high ligation of the hernia sac, 14 patients had recurrence within 2 years after surgery. After analysis, 14 cases in the recurrence group did not recur. The preoperative incarceration rate, inner ring diameter, ligature use and age difference were statistically significant (P < 0.05). According to logistic regression multivariate analysis, an inner ring diameter ≥ 1.0 cm, the use of an absorbable ligature line and age > 3 years increased the risk of postoperative recurrence in children with inguinal hernia after laparoscopic high ligation of the hernia sac (P < 0.05). CONCLUSION: Laparoscopic surgery for indirect inguinal hernia in children has the advantages of low trauma and a rapid postoperative recovery. An inner ring diameter ≥ 1.0 cm, the use of absorbable ligature, and age > 3 years may increase the risk of recurrence after laparoscopic high ligation of the hernia sac.

TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways.

The exact mechanism by which knockout of Toll-like receptor 4 (TLR4) attenuates the liver injury remains unclear. The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation (BDL)-induced liver cholestatic injury and the underlying mechanism. Wild type (WT) mice and TLR4 knockout (TLR4-KO) mice were used for the establishment of the BDL model. Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups. The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice. The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids- and choline-related metabolites. After BDL, the amino acids- and choline-related metabolites, especially choline and 3-hydroxybutyrate, were significantly increased in WT mice (both in serum and liver), but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD. In conclusion, TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.

Trace Biomolecule Detection with Functionalized Janus Particles by Rotational Diffusion.

Cytokines are small proteins secreted by cells in innate and adaptive immune systems. Abnormal cytokine secretion is often regarded as an early cue of dysregulation of homeostasis due to diseases or infections. Early detection allows early medical intervention. In this study, a natural phenomenon called rotational Brownian motion was characterized by Janus particles and its potential use in detection of trace biomolecules explored. Through the functionalization of the Janus particles with an antibody, the target cytokine, that is, tumor necrosis factor-α, was measured in terms of rotational diffusion. Rotational diffusion is highly sensitive to the particle volume change according to the Stokes-Einstein-Debye relation and can be quantified by blinking signal. Accordingly, 1 µm half-gold and half-fluorescent microbeads were conjugated with 200 nm nanobeads through sandwiched immunocomplexes. The light source, lead time for stabilization, and purification were investigated for optimization. Particle images can be captured with green light at 5 Hz within 300 s. Under such conditions, the functionalized Janus particles eventually achieved a limit of detection of 1 pg/mL. The rotational diffusometry realized by Janus particles was power-free and feasible for ultrasensitive detection, such as early disease detection.

Investigation of Micro-volume Viscosity with Janus Microbeads Based on Rotational Brownian Motion.

Viscosity is an important property of liquids. A viscosity change of aqueous substances that deviates from their normal levels usually implies a compromise in quality due to degradation or microorganism proliferation. Monitoring of macro-scale viscosity can be simply realized by various conventional tools, such as rotational viscometers, capillary tubes, falling bodies, and so forth. Nevertheless, today, micro-volume viscosity measurement remains a challenging endeavor, resulting in rare, expensive, or difficult-to-obtain samples not very well studied. For this reason, a novel technique for micro-viscosity based on rotational Brownian motion is presented in this paper. Janus microbeads were made by coating fluorescent polystyrene beads with gold film. Taking advantage of the bead configuration of half gold/half fluorescence, the rotational Brownian signal was expressed in terms of blinking fluorescent intensity. The characteristic correlation time was derived from the blinking intensity of trace amounts of a selected medium over a certain time period, and results were correlated with viscosity. Given a volume of only 2 µL for each measurement, calibration of a series of glycerol⁻water mixtures (100%⁻1% (v/v) water content) yielded good agreement with the expected viscosity predictions over the range of 0.8⁻574.8 cP. Five common oil products, including lubricant oil, baby oil, food oil, olive oil, and motor oil, were further investigated to demonstrate the feasibility and practicability of the proposed technique. Data measured by the rotational Brownian motion-based diffusometer were comparable with those measured by a commercial rotational viscometer. The method also explicitly showed viscosity degradation after the oils were heated at a high temperature of over 100 °C for 10 min. Evaluation proved the proposed Janus microbead-enabled rotational diffusometric technique to be a promising approach for rapid and micro-scale viscosity measurement.

Detecting trypsin at liquid crystal/aqueous interface by using surface-immobilized bovine serum albumin.

We report a new mechanism for liquid crystal (LC)-based sensor system for trypsin detection. In this system, bovine serum albumin (BSA) was immobilized on gold grids as the enzymatic substrate. When the BSA-modified grid was filled with LC and immersed in the solution containing trypsin, the peptide bonds of BSA were hydrolyzed and peptide fragments were desorbed from the surface of gold grid, which disrupted the orientation of LC at the vicinity and resulted in a dark-to-bright transition of optical image of LCs. By using this mechanism, the limit of detection (LOD) of trypsin is 10 ng/mL, and it does not respond to thrombin and pepsin. Besides, the cleavage behavior on gold surfaces was directly visualized by the scanning photoelectron microscopy (SPEM), in particular for the chemical composition identification and element-resolved image. The loss of BSA fragments and the enhancement of Au photoelectron signal after trypsin cleavage were corresponding to the proposed mechanism of the LC-based sensor system. Because the signals reported by LC can be simply interpreted through the human naked-eye, it provides a simple method for fast-screening trypsin activity in aqueous solution.

Strengthening of back muscles using a module of flexible strain sensors.

This research aims at developing a flexible strain module applied to the strengthening of back muscles. Silver films were sputtered onto flexible substrates to produce a flexible sensor. Assuming that back muscle elongation is positively correlated with the variations in skin surface length, real-time resistance changes exhibited by the sensor during simulated training sessions were measured. The results were used to identify the relationship between resistance change of sensors and skin surface stretch. In addition, muscle length changes from ultrasound images were used to determine the feasibility of a proof of concept sensor. Furthermore, this module is capable of detecting large muscle contractions, some of which may be undesirable for the prescribed training strategy. Therefore, the developed module can facilitate real-time assessments of the movement accuracy of users during training, and the results are instantly displayed on a screen. People using the developed training system can immediately adjust their posture to the appropriate position. Thus, the training mechanism can be constructed to help user improve the efficiency of back muscle strengthening.

Identifying discriminative amino acids within the hemagglutinin of human influenza A H5N1 virus using a decision tree.

Recently, the H5N1 virus has had an increasingly important impact on human life. This is because more and more people are becoming infected with this virus, and the possibility of a serious pandemic with human to human transmission is looming. This might occur if the genome of this influenza virus mutates either by antigenic drift or by antigenic shift, especially if there is a mutation of the hemagglutinin (HA) glycoprotein. The HA is the surface glycoprotein, and it binds to sialic acid of the host cell surface receptor. Thus, the combination of HA and sialic acid are central to whether influenza virus infects humans. In this study, we selected 497 HA protein sequences from the National Center for Biotechnology Information (NCBI) Influenza Resource database, and used a decision tree method to identify discriminative amino acids in the HA protein sequences that may possibly influence the binding of HA to sialic acid. Four such amino acid positions at 54, 55, 241, and 281 were identified and these may play an important role in infection by H5N1 influenza virus.