AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin-based chemotherapy. As a plasma membrane adhesion molecule, amphoterin-induced gene and ORF-2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin-induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin-induced activation of (caspase-8 and caspase-9)/caspase-3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME-mediated pyroptosis.

Facile fabrication of ordered discontinuous nanotopography on photosensitive substrates for enhanced neuronal differentiation.

Controlling the development and morphology of neurons is important for basic neuroscience research as well as for applications in nerve regeneration and neural interfaces. Various studies have shown that nanoscale topographies can promote the development of neuronal cells and the differentiation of neural stem cells; however, the fabrication of these nanotopographical features often involves expensive and sophisticated techniques. Here, we employ nanosphere lens lithography combined with UV-LED technology to create nanopatterns on an SU-8 photoresist. We develop a facile method to create a reusable polystyrene nanosphere (PS-NS) lens array by the spontaneous formation of a hexagonal close-packed array of PS-NSs at a water-air interface and its subsequent transfer to a polydimethylsiloxane carrier film without using any special equipment. We show that this simple technique can create ordered arrays of nanodots on an SU-8 film, the dimensions of which can be controlled by the size of the PS-NSs. When used as a substrate for the neuronal differentiation of pheochromocytoma (PC12) cells, the nanopatterned SU-8 films exhibit enhanced differentiation parameters with respect to conventional tissue culture plastic as compared with their flat counterparts. The method proposed here can greatly facilitate the nanopatterning of various photosensitive substrates for the development of implants for nerve regeneration and neural interfacing.

Delayed grafting for banked skin graft in lymph node flap transfer.

Over the last decade, lymph node flap (LNF) transfer has turned out to be an effective method in the management of lymphoedema of extremities. Most of the time, the pockets created for LNF cannot be closed primarily and need to be resurfaced with split thickness skin grafts. Partial graft loss was frequently noted in these cases. The need to prevent graft loss on these iatrogenic wounds made us explore the possibility of attempting delayed skin grafting. We have herein reported our experience with delayed grafting with autologous banked split skin grafts in cases of LNF transfer for lymphoedema of the extremities. Ten patients with International Society of Lymphology stage II-III lymphoedema of upper or lower extremity were included in this study over an 8-month period. All patients were thoroughly evaluated and subjected to lymph node flap transfer. The split skin graft was harvested and banked at the donor site, avoiding immediate resurfacing over the flap. The same was carried out in an aseptic manner as a bedside procedure after confirming flap viability and allowing flap swelling to subside. Patients were followed up to evaluate long-term outcomes. Flap survival was 100%. Successful delayed skin grafting was done between the 4th and 6th post-operative day as a bedside procedure under local anaesthesia. The split thickness skin grafts (STSG) takes more than 97%. One patient needed additional medications during the bedside procedure. All patients had minimal post-operative pain and skin graft requirement. The patients were also reported to be satisfied with the final aesthetic results. There were no complications related to either the skin grafts or donor sites during the entire period of follow-up. Delayed split skin grafting is a reliable method of resurfacing lymph node flaps and has been shown to reduce the possibility of flap complications as well as the operative time and costs.

The combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap for breast reconstruction.

BACKGROUND: Surgical options for breast reconstruction include alloplastic and autogenous reconstructions. In autologous cases where the abdomen is not a suitable primary donor site, secondary donor sites such as the thigh or buttock are considered. The aim of this report is to describe a novel approach, the combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap, aimed at medium to large volume breast reconstruction, with a single donor site used per breast. METHODS: Between January 2011 and June 2013, 32 consecutive unilateral immediate breast reconstruction cases were performed using free flaps. In nine cases, patients had previously undergone abdominal surgery, therefore abdominal flaps were excluded and TUGPAP flaps were performed. The TUGPAP flap consisted of the combination of two well-described flaps: the transverse upper gracilis (TUG) and the profunda artery perforator (PAP) flap. All TUGPAP flaps were based on two pedicles: the ascending branch of the medial circumflex femoral artery (MCFA) for the TUG component, and the profunda artery perforator itself for the PAP component. RESULTS: The mean size of the harvested skin paddle was 28.6 × 8 cm2 (range, 27 × 7 cm2 to 30 × 9 cm2). The average length of the TUG flap pedicle was 7 cm (range, 6-8 cm) and the PAP flap pedicle was 9 cm (range, 8.5-10 cm). The flap survival rate was 100% with no re-exploration, and no partial flap loss. Post-operatively there was one case of persistent donor site seroma, which was managed conservatively. CONCLUSION: With appropriate patient selection and surgical technique the TUGPAP flap could be a valuable option as an alternative method for autologous breast reconstruction. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015.

Impedimetric monitoring of IGF-1 protection of in vitro cortical neurons under ischemic conditions.

Microelectrode arrays (MEAs) incorporated with the electric cell substrate impedance sensing (ECIS) technique provide a method for acquiring cellular electrophysiological information, which is useful for the time-course monitoring of cellular outgrowth and damage. This research utilizes the ECIS technique for monitoring the time-course impedimetric changes in normal and insulin-like growth factor 1 (IGF-1)-protected cortical neurons under the ischemic insult of oxygen glucose deprivation (OGD) created in a microperfusion environment. The neuronal apoptosis is reflected by the relatively low cell viability (28 ± 11.5 %) after 30-min OGD followed by 24 h of re-oxygenation. Also the hyperpolarization phase of mitochondrial membrane potential (MMP) occurs during 2 h of the re-oxygenation period. In contrast, cortical neurons treated with 50 and 100 ng/mL IGF-1 show higher survival rates of 45 ± 5.2 % and 49 ± 9.2 %, respectively, and no occurrence of the hyperpolarization of MMP during the re-oxygenation period. The ECIS results demonstrate that the measured impedance of cortical neurons decreased from 826 ± 86 kΩ to 224 ± 32 kΩ due to cell detachment under the insult of OGD. The measured impedance of IGF-1-protected cortical neurons slowly decreased to about 50 % of the original value (560 ± 45 kΩ for 50 ng/mL and 593 ± 44 kΩ for 100 ng/mL) compared to saline control of 232 ± 37 kΩ, which indicates improved cell adhesion under OGD conditions. The time-course impedimetric results show that the proposed ECIS-based MEAs platform incorporated with a microperfusion environment can be used for the real-time monitoring of cortical neurons under in vitro OGD and the IGF-1 protective effect against OGD-induced ischemic neuronal death.

Suppression and interpersonal harmony: a cross-cultural comparison between Chinese and European Americans.

Based on Markus and Kitayama's (1991) theory, this study was conducted to examine whether the association between emotional suppression and interpersonal harmony would be moderated by cultural group (i.e., Chinese and European Americans) and an Asian cultural value (i.e., emotional self-control). A total of 451 college students (205 Chinese and 246 European Americans) participated in this study. As expected, results indicated that the association between emotional suppression and interpersonal harmony was significantly positive for Chinese but not significant for European Americans. Similarly, when emotional self-control was examined as a moderator, the results still confirmed our hypotheses. That is, the association between emotional suppression and interpersonal harmony was significantly positive for those with stronger endorsement of emotional self-control but not for those with weaker endorsement of emotional self-control. Furthermore, we examined whether the above results could be replicated when forbearance (a construct similar to suppression) and distress disclosure (a construct opposite to suppression) were examined. The results showed the same pattern for forbearance and distress disclosure when cultural group or emotional self-control served as the moderator. The convergence of findings increased the robustness of our results. Finally, our data suggest that individuals from Eastern, interdependent cultures (e.g., Chinese) tend to value emotional suppression to preserve interpersonal harmony; individuals from Western, independent cultures may or may not necessarily suppress their emotions for this purpose. A comprehensive understanding of the different meanings of a specific strategy (i.e., emotional suppression) in different cultural contexts is important to promote effective cross-cultural counseling.

Hierarchically patterned polyurethane microgrooves featuring nanopillars or nanoholes for neurite elongation and alignment.

Surface micro- and nanostructures profoundly affect the functional performance of nerve regeneration implants by modulating neurite responses. However, few studies have investigated the impact of discrete nanostructures, such as nanopillars and nanoholes, and their combination with microgrooves on neurite outgrowth and alignment. Furthermore, numerous techniques have been developed for surface micro-/nanopatterning, but simple and low-cost approaches are quite limited. In this work, we show that nanopillars and nanoholes, and their combination with microgrooves, can be patterned on polyurethane (PU) films using a low-cost, reusable photoresist master mold prepared via nanosphere lens lithography and UV-LED photolithography, with specific "reinforcement" methods for overcoming the inherent drawbacks of using photoresist masters. We show that the PU nanopillars and nanoholes increase the neurite length of pheochromocytoma 12 (PC12) cells through unique growth cone interactions. Moreover, we demonstrate, for the first time, that hierarchically patterned nano-/microstructured PU films enhance both PC12 neurite elongation and alignment, showing the potential use of our proposed method for the micro-/nanopatterning of polymers for nerve tissue engineering.

Detection of lactate in human sweat via surface-modified, screen-printed carbon electrodes.

Real-time and continuous monitoring of lactate levels in sweat has been used as an indicator of physiological information to evaluate exercise outcomes and sports performance. We developed an optimal enzyme-based biosensor to detect the concentrations of lactate in different fluids (i.e., a buffer solution and human sweat). The surface of the screen-printed carbon electrode (SPCE) was first treated with oxygen plasma and then surface-modified by lactate dehydrogenase (LDH). The optimal sensing surface of the LDH-modified SPCE was identified by Fourier transform infrared spectroscopy and electron spectroscopy for chemical analysis. After connecting the LDH-modified SPCE to a benchtop E4980A precision LCR meter, our results showed that the measured response was dependent on the lactate concentration. The recorded data exhibited a broad dynamic range of 0.1-100 mM (R2 = 0.95) and a limit of detection of 0.1 mM, which was unachievable without the incorporation of redox species. A state-of-the-art electrochemical impedance spectroscopy (EIS) chip was developed to integrate the LDH-modified SPCE for a portable bioelectronic platform in the detection of lactate in human sweat. We believe the optimal sensing surface can improve the sensitivity of lactate sensing in a portable bioelectronic EIS platform for early diagnosis or real-time monitoring during different physical activities.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

A Multimodality Electrochemical and Impedance Spectroscopy System-on-a-Chip With Temperature Sensing and Impedance-Boosting Techniques.

This article presents a multimodal electrochemical sensing system-on-chip (SoC), including the functions of cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and temperature sensing. CV readout circuitry achieves an adaptive readout current range of 145.5 dB through an automatic range adjustment and resolution scaling technique. EIS has an impedance resolution of 9.2 m Ω/√ Hz at a sweep frequency of 10 kHz and an output current of up to 120 µA. With an impedance boost mechanism, the maximum detectable load impedance is extended to 22.95 k Ω, while the total harmonic distortion is less than 1%. A resistor-based temperature sensor using a swing-boosted relaxation oscillator can achieve a resolution of 31 mK in 0-85 °C. The design is implemented in a 0.18 µm CMOS process. The total power consumption is 1 mW.

Advisory working alliance, perceived English proficiency, and acculturative stress.

The aim of this study was to examine the moderators of (a) general or cross-cultural advisory working alliances and (b) perceived English proficiency on the association between acculturative stress and psychological distress. A total of 143 East Asian international students completed an online survey. Results from a hierarchical regression indicated significant three-way interactions of (a) General Advisory Working Alliances × Perceived English Proficiency × Acculturative Stress on Psychological Distress and (b) Cross-Cultural Advisory Working Alliances × Perceived English Proficiency × Acculturative Stress on Psychological Distress. Specifically, the present results indicated that acculturative stress was significantly associated with psychological distress only when students perceived lower English proficiency and had a stronger general or cross-cultural advisory working alliance. However, acculturative stress was not significantly related to psychological distress when these students perceived lower English proficiency and had a weaker advisory working alliance (i.e., general or cross-cultural). In addition, acculturative stress was also not significantly related to psychological distress when these students perceived higher English proficiency and had a stronger or weaker advisory working alliance (i.e., general or cross-cultural).

Investigation into the effect of varied functional biointerfaces on silicon nanowire MOSFETs.

A biocompatible and functional interface can improve the sensitivity of bioelectronics. Here, 3-aminopropyl trimethoxysilane (APTMS) and 3-mercaptopropyl trimethoxysilane (MPTMS) self-assembled monolayers (SAMs) were independently modified on the surface of silicon nanowire metal-oxide-semiconductor field effect transistors (NW-MOSFETs). Those SAMs-modified silicon NW-MOSFETs were used to discriminate various pH solutions and further verify which modified regime was capable of providing better electrical signals. The APTMS-SAM modified NW-MOSFETs showed better electrical responses in pH sensing. Biomolecules on APTMS-SAM modified NW-MOSFETs also gave better signals for the corresponding proteind in physiological buffer solutions. Atomic force microscopy (AFM) clarified those electrical phenomena and found biomolecules on APTMS-SAM were relatively uniformly modified on NW-MOSFETs. Our results showed that more uniform modification contributed to better signal response to protein interactions in physiological buffer solutions. It suggests that suitable surface modifications could profoundly affect the sensing response and sensitivity.

Wireless Multimodality Sensing System-on-a-Chip With Time-Based Resolution Scaling Technique and Analog Waveform Generator in 0.18 µm CMOS for Chronic Wound Care.

Multimodal sensing can provide a comprehensive and accurate diagnosis of biological information. This paper presents a fully integrated wireless multimodal sensing chip with voltammetric electrochemical sensing at a scanning rate range of 0.08-400 V/s, temperature monitoring, and bi-phasic electrical stimulation for wound healing progress monitoring. The time-based readout circuitry can achieve a 1-20X scalable resolution through dynamic threshold voltage adjustment. A low-noise analog waveform generator is designed using current reducer techniques to eliminate the large passive components. The chip is fabricated via a 0.18 µm CMOS process. The design achieves R2 linearity of 0.995 over a wide current detection range (2 pA-12 µA) while consuming 49 µW at 1.2 V supply. The temperature sensing circuit achieves a 43 mK resolution from 20 to 80 degrees. The current stimulator provides an output current ranging from 8 µA to 1 mA in an impedance range of up to 3 kΩ. A wakeup receiver with data correlators is used to control the operation modes. The sensing data are wirelessly transmitted to the external readers. The proposed sensing IC is verified for measuring critical biomarkers, including C-reactive protein, uric acid, and temperature.

A Two-Electrode, Double-Pulsed Sensor Readout Circuit for Cardiac Troponin I Measurement.

This paper presents a pulse-stimulus sensor readout circuit for use in cardiovascular disease examinations. The sensor is based on a gold nanoparticle plate with an antibody post-modification. The proposed system utilizes gated pulses to detect the biomarker Cardiac Troponin I in an ionic solution. The characteristic of the electrostatic double-layer capacitor generated by the analyte is related to the concentration of Cardiac Troponin I in the solvent. After sensing by the transistor, a current-to-frequency converter (I-to-F) and delay-line-based time-to-digital converter (TDC) convert the information into a series of digital codes for further analysis. The design is fabricated in a 0.18-µm standard CMOS process. The chip occupies an area of 0.92 mm2 and consumes 125 µW. In the measurements, the proposed circuit achieved a 1.77 Hz/pg-mL sensitivity and 72.43 dB dynamic range.

Delay QoS and MAC Aware Energy-Efficient Data-Aggregation Routing in Wireless Sensor Networks.

By eliminating redundant data flows, data aggregation capabilities in wireless sensor networks could transmit less data to reduce the total energy consumption. However, additional data collisions incur extra data retransmissions. These data retransmissions not only increase the system energy consumption, but also increase link transmission delays. The decision of when and where to aggregate data depends on the trade-off between data aggregation and data retransmission. The challenges of this problem need to address the routing (layer 3) and the MAC layer retransmissions (layer 2) at the same time to identify energy-efficient data-aggregation routing assignments, and in the meantime to meet the delay QoS. In this paper, for the first time, we study this cross-layer design problem by using optimization-based heuristics. We first model this problem as a non-convex mathematical programming problem where the objective is to minimize the total energy consumption subject to the data aggregation tree and the delay QoS constraints. The objective function includes the energy in the transmission mode (data transmissions and data retransmissions) and the energy in the idle mode (to wait for data from downstream nodes in the data aggregation tree). The proposed solution approach is based on Lagrangean relaxation in conjunction with a number of optimization-based heuristics. From the computational experiments, it is shown that the proposed algorithm outperforms existing heuristics that do not take MAC layer retransmissions and the energy consumption in the idle mode into account.

A Novel Energy-Efficient MAC Aware Data Aggregation Routing in Wireless Sensor Networks.

Embedding data-aggregation capabilities into sensor nodes of wireless networks could save energy by reducing redundant data flow transmissions. Existing research describes the construction of data aggregation trees to maximize data aggregation times in order to reduce data transmission of redundant data. However, aggregation of more nodes on the same node will incur significant collisions. These MAC (Media Access Control) layer collisions introduce additional data retransmissions that could jeopardize the advantages of data aggregation. This paper is the first to consider the energy consumption tradeoffs between data aggregation and retransmissions in a wireless sensor network. By using the existing CSMA/CA (Carrier Sense Multiple Access with Collision Avoidance) MAC protocol, the retransmission energy consumption function is well formulated. This paper proposes a novel non-linear mathematical formulation, whose function is to minimize the total energy consumption of data transmission subject to data aggregation trees and data retransmissions. This solution approach is based on Lagrangean relaxation, in conjunction with optimization-based heuristics. From the computational experiments, it is shown that the proposed algorithms could construct MAC aware data aggregation trees that are up to 59% more energy efficient than existing data aggregation algorithms.

Exploring key factors in the choice of e-health using an asthma care mobile service model.

Asthma care mobile service (ACMS) is a care platform for asthma patients using mobile phones to monitor asthma patients' real-time conditions. The anticipated benefits and development of the healthcare network platform rely on people's adoptive willingness and behavioral intention. The goal of this study is to understand and predict patients' acceptance behavior for ACMS as an application of e-health. The study is based on the technology acceptance model and integrates "subjective norm" and "innovativeness" to understand and predict the patient's attitude and behavioral intention. Employing a convenience sampling method, valid questionnaire responses were obtained from 229 patients. A confirmatory factor analysis examined the reliability and validity of the measurement model, while the structural equation modeling technique was employed to interpret the causal model. The model was used in the study to explain and predict the utilization of ACMS with a high explanatory power as a good-fit model. The results indicated the most critical factor that affects behavioral intentions related to ACMS is user attitude, followed by perceived usefulness, subjective norm, perceived ease of use, and innovativeness. The results provide the government developing high-tech, preventive medicine strategies the necessary data to define an appropriate policy to use in attracting greater participation in the effort.

Exploring the key factors in the choice of home telehealth by using the health belief model.

The health belief model (HBM) was used in this study to identify and explore key factors in home telehealth. This study interviewed 369 people in Taiwan. A confirmatory factor analysis examined the reliability and validity of the measurement model, while the structural equation modeling technique was used to interpret the causal model. Lastly, multivariate analysis of variance and Scheffe's test were used to find the relationship between demographic parameters and behavioral intention to use home telehealth. The results reveal that HBM can be considered a good-fit model. This study considers the critical factors related to home telehealth that affect users. It facilitates the formation of a more comprehensive overall evaluation system.

Demonstration of disinfection procedure for the development of accurate blood glucose meters in accordance with ISO 15197:2013.

Despite measures to reduce disease transmission, a risk can occur when blood glucose meters (BGMs) are used on multiple individuals or by caregivers assisting a patient. The laboratory and in-clinic performance of a BGM system before and after disinfection should be demonstrated to guarantee accurate readings and reliable control of blood glucose (BG) for patients. In this study, an effective disinfection procedure, conducting wiping 10 times to assure a one minute contact time of the disinfectant on contaminated surface, was first demonstrated using test samples of the meter housing materials, including acrylonitrile butadiene styrene (ABS), polymethyl methacrylate (PMMA), and polycarbonate (PC), in accordance with ISO 15197:2013. After bench studies comprising 10,000 disinfection cycles, the elemental compositions of the disinfected ABS, PMMA, and PC samples were almost the same as in the original samples, as indicated by electron spectroscopy for chemical analysis. Subsequently, the validated disinfection procedure was then directly applied to disinfect 5 commercial BGM systems composed of ABS, PMMA, or PC to observe the effect of the validated disinfection procedure on meter accuracy. The results of HBsAg values after treatment with HBV sera and disinfectant wipes for each material were less than the LoD of each material of 0.020 IU/mL. Before and after the multiple disinfection cycles, 900 of 900 samples (100%) were within the system accuracy requirements of ISO 15197:2013. All of the systems showed high performance before and after the series of disinfection cycles and met the ISO 15197:2013 requirements. In addition, our results demonstrated multiple cleaning and disinfection cycles that represented normal use over the lifetime of a meter of 3-5 years. Our validated cleaning and disinfection procedure can be directly applied to other registered disinfectants for cleaning commercial BGM products in the future.

A comparison of MICU survival prediction using the logistic regression model and artificial neural network model.

Under the policy of restraint in medical expenditure and with the dual pressures of medical technology development and population aging, the critical care services will exert even greater pressure on the limited medical resources. Therefore, the objective of this study is to compare the abilities of two models, the Logistic Regression Model and the Neural Network Model, to predict the survival of critical care patients, in order to provide a more ethical and objective survival prediction system, as well as to promote more effective management of the resources of the medical intensive care unit (MICU). The two models use the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) and Glasgow Coma Scale (GCS) scores of 1,496 patients stayed who in the MICU of a Taiwan medical center during January 2002-January 2004 to conduct the survival prediction. The study results show that the Neural Network Model has a better predictive ability than the Logistic Regression Model both with regard to the survivors (86.7%, n = 361) and with regard to the entire population of patients studied (74.7%, n = 498).