Frequency and characteristics of patients with bispectral index values of 60 or higher during the induction and maintenance of general anesthesia with remimazolam.

In Korea, the approved anesthetic regimen of remimazolam starts with 6 mg/kg/h or 12 mg/kg/h until loss of consciousness, followed by maintenance at 1-2 mg/kg/h. Some patients receiving remimazolam for general anesthesia experience occasional difficulty maintaining bispectral index (BIS) value ˂ 60. This retrospective study aimed to analyze the data from patients undergoing elective surgery under remimazolam based-general anesthesia to determine the frequency and physical characteristics of patients with BIS values ˂ 60. The criterion was established for patients with a poorly maintained BIS value < 60. The frequency and physical characteristics of patients who satisfied this criterion were investigated through their medical records. The modified Brice interview was conducted within 24 h after surgery. Among the 1500 patients included in the analysis, 61 (4.1%) met the criteria for BIS ˂ 60. Based on the modified Brice interview, none of the patients with poorly maintained BIS ˂ 60 complained of intraoperative awareness based on the modified Brice interview or exhibit specific physical characteristics. These patients accounted for less than 5% of the total population studied. Notably, physical characteristics alone are insufficient to predict such patients before surgery.

Thermally Managed, Injectable Optoelectronic Probe with Heat Dissipation Guide for Photodynamic Therapy.

The development of fabrication technologies and appearance of new materials has resulted in dramatic increase in the performance of electronic devices, while the overall size has decreased. Recent electronic devices made of micro/nano-size components show high efficiency and outstanding performance with compact size, but these devices have revealed several fatal problems. In particular, the isolated heat that is generated by numerous components concentrated in a limited small area at high density, such as bio-integrated devices, is an issue that needs to be urgently addressed, because it is closely related to the performance and lifetime of electronic devices. To solve these problems, the microscale light emitting diode (µLED)-based neural probe is introduced on an injectable heat dissipation guide. The heat dissipation guide is made of boron nitride (BN) nanomaterials with high thermal conductivity. The heat management noticeably improves the optical output performance of the µLEDs, in which BN effectively dissipates heat, and allows enhanced lighting from the LEDs to be transmitted through brain tissue without thermal damage. Moreover, it shows remarkable improvement in the therapeutic effect of photodynamic therapy of mouse cancer cells.

Solvent-Assisted Filling of Liquid Metal and Its Selective Dewetting for the Multilayered 3D Interconnect in Stretchable Electronics.

As stretchable electronics are rapidly developing and becoming complex, the requirement for stretchable, multilayered, and large-area printed circuit boards (PCBs) is emerging. This demands a stretchable electrode and its vertical interconnect access (via) for 3-dimensional (3D) connectivity between layers. Here, we demonstrate solvent-assisted liquid metal (LM) filling into the submicrometer channel (∼400 nm), including via-hole filling and selective dewetting of LM. We provide the theoretical background of solvent-assisted LM filling and selective dewetting and reveal the osmotic pressure arising from anomalous mass transport phenomena, case II diffusion, which drives negative pressure, the spontaneous pulling of LM into the open channel. Also, we suggest design criteria for the geometry and dimension of LM interconnects to obtain structural stability without dewetting, based on the theoretical and computational background. We demonstrate a simple stretchable near-field communication (NFC) device including transferred micrometer-size light-emitting diodes (LEDs) with only 230 µm to the stretchable liquid metal PCB, without any soldering process. The device operates stably under repetitive stretching and releasing (∼50% uniaxial strain) due to the stable connection through the LM via between the upper and lower layers. Finally, we propose a concept for modular-type stretchable electronics, based on the cohesive liquid nature of LM. As a building block, the functional module can be easily removed from a mainframe, and replaced by another functional module, to suit user demand.

Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.

BACKGROUND: Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues. METHODS: Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in the body to potentiate antitumor immunity with mild visible light. RESULTS: The micro-LED is prepared by stacking one to four micro-scale LEDs (100 µm) on a needle-shape photonic device, which can be directly implanted into the core part of the tumor tissue. The photonic device with four LEDs efficiently elicits sufficient light output powers without thermal degradation and promotes reactive oxygen species (ROS) from a photosensitizer (verteporfin; VPF). After the intravenous injection of VPF in colon tumor-bearing mice, the tumor tissues are irradiated with optimal light intensity using an implanted micro-LED. While tumor tissues under intense visible light causes immunosuppression by severe inflammatory responses and regulatory T cell activation, mild visible light elicits potent ICD in tumor cells, which promotes dendritic cell (DC) maturation and T cell activation. The enhanced therapeutic efficacy and antitumor immunity by micro-LED guided PDT with mild visible light are assessed in colon tumor models. Finally, micro-LED guided PDT in combination with immune checkpoint blockade leads to 100% complete tumor regression and also establishes systemic immunological memory to prevent the recurrence of tumors. CONCLUSION: Collectively, this study demonstrates that micro-LED guided PDT with mild visible light is a promising strategy for cancer immunotherapy.

Antinociceptive and Anti-Inflammatory Effects of Recombinant Crotamine in Mouse Models of Pain.

Crotamine, a toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus, has been reported to have antinociceptive effects. We purified recombinant crotamine expressed in Escherichia coli and investigated its antinociceptive and anti-inflammatory effects using the hot-plate test, acetic-acid-induced writhing method, and formalin test in mice. Recombinant crotamine was administered intraperitoneally (0.04-1.2 mg kg-1) or intraplantarly (0.9-7.5 µg 10 µL-1) before the tests. The paw volume was measured with a plethysmometer. To evaluate the antagonistic and anti-inflammatory effects of naloxone, subcutaneous naloxone (4 mg kg-1) or intraplantar naloxone (5 µg 10 µL-1) was administered before recombinant crotamine. For tumor necrosis factor (TNF)-α assays, blood was drawn 3 h after formalin injection and measured using enzyme-linked immunosorbent assay. Intraperitoneal and intraplantar recombinant crotamine had antinociceptive and anti-inflammatory effects, neither of which were affected by pre-treatment with naloxone. The mean serum TNF-α levels were significantly lower in the intraperitoneal recombinant crotamine (0.4 and 1.2 mg kg-1) or intraplantar (2.5 and 7.5 µg 10 µL-1) recombinant crotamine groups than in the saline group and were not affected by naloxone pre-treatment. In conclusion, recombinant crotamine possesses significant antinociceptive and anti-inflammatory effects that do not appear to be related to the opioid receptor. The antinociceptive and anti-inflammatory effects of intraperitoneal or intraplantar recombinant crotamine are related to TNF-α.

Effects of Perioperative Inflammatory Response in Cervical Cancer: Laparoscopic versus Open Surgery.

There are few studies between postoperative neutrophil to lymphocyte ratio (NLR) and survival in cervical cancer. We compared postoperative changes in NLR according to surgical methods and analyzed the effect of these changes on 5-year mortality of cervical cancer patients. A total of 929 patients were assigned to either the laparoscopic radical hysterectomy (LRH) (n = 721) or open radical hysterectomy (ORH) (n = 208) group. Propensity score matching analysis compared the postoperative NLR changes between the two groups, and multivariate logistic regression analysis evaluated the association between NLR changes and 5-year mortality. Surgical outcomes between the two groups were also compared. In the LRH group, NLR changes at postoperative day (POD) 0 and POD 1 were significantly lower than in the ORH group after matching (NLR change at POD 0, 10.4 vs. 14.3, p < 0.001; NLR change at POD 1, 3.5 vs. 5.4, p < 0.001). In multivariate logistic regression analysis, postoperative NLR change was not associated with 5-year mortality (2nd quartile: OR 1.55, 95% CI 0.56-4.29, p = 0.401; 3rd quartile: OR 0.90, 95% CI 0.29-2.82, p = 0.869; 4th quartile: OR 1.40, 95% CI 0.48-3.61, p = 0.598), whereas preoperative NLR was associated with 5-year mortality (OR 1.23, 95% CI 1.06-1.43, p = 0.005). After matching, there were no significant differences in surgical outcomes between the two groups. There were significantly fewer postoperative changes of NLR in the LRH group. However, the extent of these NLR changes was not associated with 5-year mortality. By contrast, preoperative NLR was associated with 5-year mortality.

Association between Neutrophil-Lymphocyte Ratio and Herpes Zoster Infection in 1688 Living Donor Liver Transplantation Recipients at a Large Single Center.

Liver transplantation (LT) is closely associated with decreased immune function, a contributor to herpes zoster (HZ). However, risk factors for HZ in living donor LT (LDLT) remain unknown. Neutrophil-lymphocyte ratio (NLR) and immune system function are reportedly correlated. This study investigated the association between NLR and HZ in 1688 patients who underwent LDLT between January 2010 and July 2020 and evaluated risk factors for HZ and postherpetic neuralgia (PHN). The predictive power of NLR was assessed through the concordance index and an integrated discrimination improvement (IDI) analysis. Of the total cohort, 138 (8.2%) had HZ. The incidence of HZ after LT was 11.2 per 1000 person-years and 0.1%, 1.3%, 2.9%, and 13.5% at 1, 3, 5, and 10 years, respectively. In the Cox regression analysis, preoperative NLR was significantly associated with HZ (adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.09; p = 0.005) and PHN (HR, 1.08; 95% CI, 1.03-1.13; p = 0.001). Age, sex, mycophenolate mofetil use, and hepatitis B virus infection were risk factors for HZ versus age and sex for PHN. In the IDI analysis, NLR was discriminative for HZ and PHN (p = 0.020 and p = 0.047, respectively). Preoperative NLR might predict HZ and PHN in LDLT recipients.

Nanoscale-Dewetting-Based Direct Interconnection of Microelectronics for a Deterministic Assembly of Transfer Printing.

As electronics dramatically advance, their components should be fabricated for miniaturized scale, and integrated on limited-size substrates with extremely high density. Current technologies for the integration and interconnection of electronics show some critical limitations in the application of microscale electronics. To address these problems, herein, a new direct and vertical interconnection driven by selective dewetting of a polymer adhesive is introduced. The interconnection system consists of the polymer adhesive and nanosized metal particles, or structured electrodes. Nanoscale-dewetting windows formed by controlling the stability and wetting property of the adhesive polymer are controlled by the interfacial property of the coated polymer adhesive. The adhesive is coated on substrate by a simple spin-coating process, and its ultraviolet curable property allows only the device-mounted parts to be selectively conductive and sticky, while the other parts form insulation and protection layers. The interconnection of the electronics and substrate by adhesive makes it possible to apply the technique to various microsize electronics with electrode size and pitch of 20 µm or less, and endure dramatic temperature change and a long-term high humidity environment. Moreover, over display comprising over 10 000 microscale light-emitting diodes (micro-LEDs), and commercialized microchips are demonstrated with monolithic integration on flexible and transparent substrate.

Injectable Biomedical Devices for Sensing and Stimulating Internal Body Organs.

The rapid pace of progress in implantable electronics driven by novel technology has created devices with unconventional designs and features to reduce invasiveness and establish new sensing and stimulating techniques. Among the designs, injectable forms of biomedical electronics are explored for accurate and safe targeting of deep-seated body organs. Here, the classes of biomedical electronics and tools that have high aspect ratio structures designed to be injected or inserted into internal organs for minimally invasive monitoring and therapy are reviewed. Compared with devices in bulky or planar formats, the long shaft-like forms of implantable devices are easily placed in the organs with minimized outward protrusions via injection or insertion processes. Adding flexibility to the devices also enables effortless insertions through complex biological cavities, such as the cochlea, and enhances chronic reliability by complying with natural body movements, such as the heartbeat. Diverse types of such injectable implants developed for different organs are reviewed and the electronic, optoelectronic, piezoelectric, and microfluidic devices that enable stimulations and measurements of site-specific regions in the body are discussed. Noninvasive penetration strategies to deliver the miniscule devices are also considered. Finally, the challenges and future directions associated with deep body biomedical electronics are explained.

Controllable Configuration of Sensing Band in a Pressure Sensor by Lenticular Pattern Deformation on Designated Electrodes.

Resistive-type pressure sensor, which are mainly utilized in industry, are easy to manufacture and are not significantly affected by external electromagnetic fields, unlike capacitive type. However, the produce signal is not linear, and it is also difficult to measure a wide range of pressures using such a sensor. Therefore, before being utilized, the extracted nonlinear data from them need to be processed by. A resistive sensor that is capable of measuring a wide range of pressure of up to 4 MPa with constant linearity is presented. Moreover it can selectively control the sensing pressure band, or act as an on/off switch, without the need for any additional computer processing.

Chronic and acute stress monitoring by electrophysiological signals from adrenal gland.

We present electrophysiological (EP) signals correlated with cellular cell activities in the adrenal cortex and medulla using an adrenal gland implantable flexible EP probe. With such a probe, we could observe the EP signals from the adrenal cortex and medulla in response to various stress stimuli, such as enhanced hormone activity with adrenocorticotropic hormone, a biomarker for chronic stress response, and an actual stress environment, like a forced swimming test. This technique could be useful to continuously monitor the elevation of cortisol level, a useful indicator of chronic stress that potentially causes various diseases.

Biosafe, Eco-Friendly Levan Polysaccharide toward Transient Electronics.

New options in the material context of transient electronics are essential to create or expand potential applications and to progress in the face of technological challenges. A soft, transparent, and cost-effective polymer of levan polysaccharide that is capable of complete, programmable dissolution is described when immersed in water and implanted in an animal model. The results include chemical analysis, the kinetics of hydrolysis, and adjustable dissolution rates of levan, and a simple theoretical model of reactive diffusion governed by temperature. In vivo experiments of the levan represent nontoxicity and biocompatibility without any adverse reactions. On-demand, selective control of dissolution behaviors with an animal model demonstrates an effective triggering strategy to program the system's lifetime, providing the possibility of potential applications in envisioned areas such as bioresorbable electronic implants and drug release systems.