Bioinspired Nanotopography for Combinatory Osseointegration and Antibacterial Therapy.

The ongoing global health has highlighted the critical issue of secondary infections, particularly antibiotic-resistant bacterial infections, which have been significant contributors to mortality rates. Orthopedic implants, while essential for trauma and orthopedic surgeries, are particularly susceptible to these infections, leading to severe complications and economic burdens. The traditional use of antibiotics in treating these infections poses further challenges including the risk of developing antibiotic-resistant bacteria. This study introduces a novel approach to combat this issue by developing nanostructured surfaces for orthopedic implants using target ion-induced plasma sputtering. Inspired by the natural design of dragonfly wings, these surfaces aim to prevent bacterial adhesion while promoting preosteoblast activity, offering a dual-function solution to the problems of bacterial infection and implant integration without relying on antibiotics. The in vitro results demonstrate the effectiveness of these bioinspired surfaces in eradicating bacteria and supporting cell proliferation and differentiation, presenting a promising alternative for the development of biomedical implants.

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological method-ologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics monitoring in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally specific drug delivery while recording activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors GRAB NE and GRAB DA , and neuropeptide sensors. We demonstrate the performance this platform for investigating neuropharmacological mechanisms in vivo and characterize its efficacy in probing precise mechanistic actions of neuroactive compounds across several rapidly evolving neuroscience domains.

Remote optogenetic control of the enteric nervous system and brain-gut axis in freely-behaving mice enabled by a wireless, battery-free optoelectronic device.

Wireless activation of the enteric nervous system (ENS) in freely moving animals with implantable optogenetic devices offers a unique and exciting opportunity to selectively control gastrointestinal (GI) transit in vivo, including the gut-brain axis. Programmed delivery of light to targeted locations in the GI-tract, however, poses many challenges not encountered within the central nervous system (CNS). We report here the development of a fully implantable, battery-free wireless device specifically designed for optogenetic control of the GI-tract, capable of generating sufficient light over large areas to robustly activate the ENS, potently inducing colonic motility ex vivo and increased propulsion in vivo. Use in in vivo studies reveals unique stimulation patterns that increase expulsion of colonic content, likely mediated in part by activation of an extrinsic brain-gut motor pathway, via pelvic nerves. This technology overcomes major limitations of conventional wireless optogenetic hardware designed for the CNS, providing targeted control of specific neurochemical classes of neurons in the ENS and brain-gut axis, for direct modulation of GI-transit and associated behaviours in freely moving animals.

Improvement of morning headache in adults with obstructive sleep apnea after positive airway pressure therapy.

The aim of this study was to evaluate the association between obstructive sleep apnea and morning headache and to assess the improvement of morning headache following positive airway pressure therapy. One hundred and sixteen participants were enrolled in this study; all of them received positive airway pressure therapy for at least 3 months. We checked the differences in various sleep apnea-related parameters according to the presence of morning headache and evaluated the improvement of morning headache following positive airway pressure therapy. Among the 116 study participants, 103 were men, with a mean age and body mass index of 50.34 ± 10.23 years and 28.00 ± 4.21 kg/m2, respectively. The severity of morning headache was higher in the severe obstructive sleep apnea group than in the mild to moderate group (2.16 ± 1.70 vs. 1.50 ± 1.57, P = 0.027). However, the various polysomnographic parameters did not significantly differ according to the presence of headache. The Epworth sleepiness scale score was significantly higher in the morning headache presence group than in the absence group (10.90 ± 5.45 vs. 8.13 ± 4.27, P = 0.003). Furthermore, a notable correlation was observed between the reduction in daytime sleepiness and the improvement in morning headache following PAP treatment (r = 0.503, P < 0.001). Morning headache significantly improved following positive airway pressure therapy (prevalence: 53.4-16.4%; severity: 1.92 ± 1.67 vs. 0.86 ± 0.80, all P < 0.001), especially in the patients with morning headache before positive airway pressure therapy. Morning headache is significantly associated with daytime sleepiness and positive airway pressure therapy improves morning headache.

A Miniaturized, Battery-Free, Wireless Wound Monitor That Predicts Wound Closure Rate Early.

Diabetic foot ulcers are chronic wounds that affect millions and increase the risk of amputation and mortality, highlighting the critical need for their early detection. Recent demonstrations of wearable sensors enable real-time wound assessment, but they rely on bulky electronics, making them difficult to interface with wounds. Herein, a miniaturized, wireless, battery-free wound monitor that measures lactate in real-time and seamlessly integrates with bandages for conformal attachment to the wound bed is introduced. Lactate is selected due to its multifaceted role in initiating healing. Studies in healthy and diabetic mice reveal distinct lactate profiles for normal and impaired healing wounds. A mathematical model based on the sensor data predicts wound closure rate within the first 3 days post-injury with ≈76% accuracy, which increases to ≈83% when pH is included. These studies underscore the significance of monitoring biomarkers during the inflammation phase, which can offer several benefits, including short-term use of wound monitors and their easy removal, resulting in lower risks of injury and infection at the wound site. Improvements in prediction accuracy can be achieved by designing mathematical models that build on multiple wound parameters such as pro-inflammatory and metabolic markers. Achieving this goal will require designing multi-analyte wound monitors.

Review of the Oscillation of Research Regulations for Bioethics in the Republic of Korea: Comparison with Japan.

The Bioethics Act in the Republic of Korea has undergone great fluctuations akin to the pendulum of a clock. Since Professor Hwang's research ethics issue, domestic embryonic stem cell research has lost its vitality. This study argues that the Republic of Korea needs a reference point that does not waiver. This study examined the characteristics of life science- and ethics-related systems in the Republic of Korea and Japan. It also examined the pendulum-like policy changes in the Republic of Korea. It then compared the strengths and weaknesses between the Republic of Korea and Japan. Finally, we proposed a system improvement strategy for the development of bioethics research in Asian countries. In particular, this study argues that the advantages of Japan's slow but stable system should be introduced.

The theoretical systems of OFDI location determinants in global north and global south economies.

With economic transformation and industrial development, Outward Foreign Direct Investment (OFDI) from southern countries has increased rapidly. The theoretical system established by global north countries with their dominant position in the international investment market has been impacted by global south countries. The existing OFDI theory has always been based on developed countries and can only explain some international investment behavior of southern countries. The Vector Error Correction Model (VECM) is applied to conduct empirical analysis for the impact of the target country's investment climate on the location determinants of OFDI, by applying China and the United States as example which is focusing on 172 countries from 2005 to 2019. The results reveal significant differences in the theoretical system of foreign investment between China and the United States. For China, investment climate factors such as energy, logistics infrastructure, and politics are discover as the main drivers of China's OFDI. However, USA's OFDI is a corporate behavior aimed at economic interests. The differences in OFDI theoretical systems and provides policy advice for northern and southern countries and departments is the major contribution of this research.

Bioresorbable, wireless, and battery-free system for electrotherapy and impedance sensing at wound sites.

Chronic wounds, particularly those associated with diabetes mellitus, represent a growing threat to public health, with additional notable economic impacts. Inflammation associated with these wounds leads to abnormalities in endogenous electrical signals that impede the migration of keratinocytes needed to support the healing process. This observation motivates the treatment of chronic wounds with electrical stimulation therapy, but practical engineering challenges, difficulties in removing stimulation hardware from the wound site, and absence of means to monitor the healing process create barriers to widespread clinical use. Here, we demonstrate a miniaturized wireless, battery-free bioresorbable electrotherapy system that overcomes these challenges. Studies based on a splinted diabetic mouse wound model confirm the efficacy for accelerated wound closure by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis. Changes in the impedance provide means for tracking the healing process. The results demonstrate a simple and effective platform for wound site electrotherapy.

Management of symptomatic cervical facet cyst with cervical interlaminar epidural block: A case report.

BACKGROUND: Symptomatic cervical facet cysts are relatively rare compared to those in the lumbar region. These cysts are usually located in the 7th cervical and 1st thoracic vertebral (C7/T1) area, and surgical excision is performed in most cases. However, facet cysts are associated with degenerative conditions, and elderly patients are often ineligible for surgical procedures. Cervical interlaminar epidural block has been used in patients with cervical radiating symptoms and achieved good results. Therefore, cervical interlaminar epidural block may be the first-choice treatment for symptomatic cervical facet cysts. CASE SUMMARY: A 70-year-old man complained of a tingling sensation in the left hand, focused on the 4th and 5th fingers, for 1 year, and posterior neck pain for over 5 mo. The patient's numeric rating scale (NRS) score was 5/10. The patient was diagnosed with symptomatic cervical facet cyst at the left C7/T1 facet joint. Fluoroscopy-guided cervical interlaminar epidural block at the C7/T1 level with 20 mg triamcinolone and 5 mL of 0.5% lidocaine was administered. The patient's symptoms improved immediately after the block, with an NRS score of 3 points. After 3 mo, his left posterior neck pain and tingling along the left 8th cervical dermatome were relieved, with an NRS score of 2. CONCLUSION: A cervical interlaminar epidural block is a good alternative for managing symptomatic cervical facet cysts.

A bioresorbable peripheral nerve stimulator for electronic pain block.

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, or biochemical effects. Optimized designs ensure that the device disappears harmlessly in the body after a desired period of use. Studies in live animal models illustrate capabilities for complete nerve block and other key features of the technology. In certain clinically relevant scenarios, such approaches may reduce or eliminate the need for use of highly addictive drugs such as opioids.

Prediction of hearing recovery in unilateral sudden sensorineural hearing loss using artificial intelligence.

Despite the significance of predicting the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL), no predictive models have been established. This study used artificial intelligence to develop prognosis models to predict recovery from ISSNHL. We retrospectively reviewed the medical data of 453 patients with ISSNHL (men, 220; women, 233; mean age, 50.3 years) who underwent treatment at a tertiary hospital between January 2021 and December 2019 and were followed up after 1 month. According to Siegel's criteria, 203 patients recovered in 1 month. Demographic characteristics, clinical and laboratory data, and pure-tone audiometry were analyzed. Logistic regression (baseline), a support vector machine, extreme gradient boosting, a light gradient boosting machine, and multilayer perceptron were used. The outcomes were the area under the receiver operating characteristic curve (AUROC) primarily, area under the precision-recall curve, Brier score, balanced accuracy, and F1 score. The light gradient boosting machine model had the best AUROC and balanced accuracy. Together with multilayer perceptron, it was also significantly superior to logistic regression in terms of AUROC. Using the SHapley Additive exPlanation method, we found that the initial audiogram shape is the most important prognostic factor. Machine/deep learning methods were successfully established to predict the prognosis of ISSNHL.

Effect of intravascular dexamethasone injection after powered intracapsular tonsillectomy and adenoidectomy in children.

PURPOSE: To compare postoperative pain, nausea and vomiting, and bleeding between intravascular dexamethasone injection group and control group among children undergoing powered intracapsular tonsillectomy and adenoidectomy (PITA). MATERIALS AND METHODS: Retrospective review of medical records was performed for pediatric patients who underwent PITA from March 1, 2017, to February 28, 2021, at a tertiary referral medical center in South Korea. Postoperative pain and nausea were measured using the visual analogue scale (VAS) from the postoperative day (POD) 0 to POD 6. The number of analgesics administered and the number of vomiting episodes were recorded in the same period. The repeatedly measured parameters were statistically analyzed between the dexamethasone group and control group. RESULTS: A total of 71 children with complete questionnaires including 44 boys and 27 girls were included, and the mean age was 7.49 ± 2.44 years. There were 33 patients in the dexamethasone group and 38 in the control group. Postoperative pain (p = 0.169) or nausea (p = 0.460) on the VAS showed no statistically significant difference between the two groups. Postoperative analgesics showed no difference between the groups (p = 0.398), and neither did postoperative vomiting (p = 0.270). In both groups, no child showed signs of postoperative bleeding. CONCLUSIONS: This study indicates that the beneficial effects of intravascular dexamethasone administration in PITA may not be evident. This might be due to the superior outcome of the PITA technique compared to total extracapsular tonsillectomy. Therefore, otolaryngologists performing PITA may not necessarily need to administer dexamethasone in children before surgery.

Accelerated biodegradation of iron-based implants via tantalum-implanted surface nanostructures.

In recent years, pure iron (Fe) has attracted significant attention as a promising biodegradable orthopedic implant material due to its excellent mechanical and biological properties. However, in physiological conditions, Fe has an extremely slow degradation rate with localized and irregular degradation, which is problematic for practical applications. In this study, we developed a novel combination of a nanostructured surface topography and galvanic reaction to achieve uniform and accelerated degradation of an Fe implant. The target-ion induced plasma sputtering (TIPS) technique was applied on the Fe implant to introduce biologically compatible and electrochemically noble tantalum (Ta) onto its surface and develop surface nano-galvanic couples. Electrochemical tests revealed that the uniformly distributed nano-galvanic corrosion cells of the TIPS-treated sample (nano Ta-Fe) led to relatively uniform and accelerated surface degradation compared to that of bare Fe. Furthermore, the mechanical properties of nano Ta-Fe remained almost constant during a long-term in vitro immersion test (~40 weeks). Biocompatibility was also assessed on surfaces of bare Fe and nano Ta-Fe using in vitro osteoblast responses through direct and indirect contact assays and an in vivo rabbit femur medullary cavity implantation model. The results revealed that nano Ta-Fe not only enhanced cell adhesion and spreading on its surface, but also exhibited no signs of cellular or tissue toxicity. These results demonstrate the immense potential of Ta-implanted surface nanostructures as an effective solution for the practical application of Fe-based orthopedic implants, ensuring long-term biosafety and clinical efficacy.

Nano-Topographical Control of Ti-Nb-Zr Alloy Surfaces for Enhanced Osteoblastic Response.

Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10-210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants.

The impact of surface treatment in 3-dimensional printed implants for early osseointegration: a comparison study of three different surfaces.

3D printing technology has been gradually applied to various areas. In the present study, 3D-printed implants were fabricated with direct metal laser sintering technique for a dental single root with titanium. The 3D implants were allocated into following groups: not treated (3D-None), sandblasted with a large grit and acid-etched (3D-SLA), and target-ion-induced plasma-sputtered surface (3D-TIPS). Two holes were drilled in each tibia of rabbit, and the three groups of implants were randomly placed with a mallet. Rabbits were sacrificed at two, four, and twelve weeks after the surgery. Histologic and histomorphometric analyses were performed for the evaluation of mineralized bone-to-implant contact (mBIC), osteoid-to-implant contact (OIC), total bone-to-implant contact (tBIC), mineralized bone area fraction occupancy (mBAFO), osteoid area fraction occupancy (OAFO), and total bone area fraction occupancy (tBAFO) in the inner and outer areas of lattice structure. At two weeks, 3D-TIPS showed significantly higher inner and outer tBIC and inner tBAFO compared with other groups. At four weeks, 3D-TIPS showed significantly higher outer OIC than 3D-SLA, but there were no significant differences in other variables. At twelve weeks, there were no significant differences. The surface treatment with TIPS in 3D-printed implants could enhance the osseointegration process in the rabbit tibia model, meaning that earlier osseointegration could be achieved.

Variation in Sleep Stability with Differences in Severity of Sleep-Disordered Breathing in Children.

OBJECTIVES: The aim of this study was to analyze the association between obstructive sleep apnea (OSA) severity and various cardiopulmonary coupling (CPC) parameters in children with OSA. STUDY DESIGN: Retrospective cross-sectional study. METHODS: A cross-sectional study was conducted among 117 children (aged 7.96 ± 3.54 years, 86 male) who underwent both full-night polysomnography (PSG) and CPC for suspicion of sleep-disordered breathing (SDB). We analyzed the association between various CPC and PSG findings. RESULTS: The apnea-hypopnea index (AHI) was negatively correlated with high frequency coupling (HFC, r = -0.374, P < .001) and very low frequency coupling (VLFC, r = -0.192, P = .038) and positively correlated with low frequency coupling (LFC, r = 0.503, P < .001), elevated low frequency coupling (e-LFC, r = 0.475, P < .001), and narrow and broad band e-LFC (e-LFCNB and e-LFCBB ; r = 0.221, P = .016 and r = 0.468, P < .001, respectively). The arousal index was negatively correlated with HFC (r = - 0.466, P < .001) and positively correlated with LFC, e-LFC, e-LFCNB , and e-LFCBB (r = 0.543, r = 0.460, r = 0.239, and r = 0.445, respectively; all P < .001). In addition, we also found a significant difference in various CPC values according to OSA severity. CONCLUSION: CPC parameters accurately reflect sleep fragmentation and OSA severity in children. Thus, we can verify objective sleep quality using CPC analysis, which is a simple method of analyzing sleep stability in children with SDB. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:435-439, 2021.

Construction of tantalum/poly(ether imide) coatings on magnesium implants with both corrosion protection and osseointegration properties.

Poly(ether imide) (PEI) has shown satisfactory corrosion protection capability with good adhesion strength as a coating for magnesium (Mg), a potential candidate of biodegradable orthopedic implant material. However, its innate hydrophobic property causes insufficient osteoblast affinity and a lack of osseointegration. Herein, we modify the physical and chemical properties of a PEI-coated Mg implant. A plasma immersion ion implantation technique is combined with direct current (DC) magnetron sputtering to introduce biologically compatible tantalum (Ta) onto the surface of the PEI coating. The PEI-coating layer is not damaged during this process owing to the extremely short processing time (30 s), retaining its high corrosion protection property and adhesion stability. The Ta-implanted layer (roughly 10-nm-thick) on the topmost PEI surface generates long-term surface hydrophilicity and favorable surface conditions for pre-osteoblasts to adhere, proliferate, and differentiate. Furthermore, in a rabbit femur study, the Ta/PEI-coated Mg implant demonstrates significantly enhanced bone tissue affinity and osseointegration capability. These results indicate that Ta/PEI-coated Mg is promising for achieving early mechanical fixation and long-term success in biodegradable orthopedic implant applications.

Comparing hemostatic resuscitation management of intraoperative massive bleeding with traumatic massive bleeding: a computer simulation.

BACKGROUND: Appropriate blood component transfusion might differ between intraoperative massive bleeding and traumatic massive bleeding in the emergency department because trauma patients initially bleed undiluted blood and replacement typically lags behind blood loss. We compared these two blood loss scenarios, intraoperative and traumatic, using a computer simulation. METHODS: We modified the multi-compartment dynamic model developed by Hirshberg and implemented it using STELLA 9.0. In this model, blood pressure changes as blood volume fluctuates as bleeding rate and transcapillary refill rate are controlled by blood pressure. Using this simulation, we compared the intraoperative bleeding scenario with the traumatic bleeding scenario. In both scenarios, patients started to bleed at a rate of 50 ml/min. In the intraoperative bleeding scenario, fluid was administered to maintain isovolemic status; however, in the traumatic bleeding scenario, no fluid was supplied for up to 30 min and no blood was supplied for up to 50 min. Each unit of packed red blood cells (PRBC) was given when the hematocrit decreased to 27%, fresh frozen plasma (FFP) was transfused when plasma was diluted to 30%, and platelet concentrate (PC) was transfused when platelet count became 50,000/ml. RESULTS: In both scenarios, the appropriate ratio of PRBC:FFP was 1:0.47 before PC transfusion, and the ratio of PRBC:FFP:platelets was 1:0.35:0.39 after initiation of PC transfusion. CONCLUSION: The ratio of transfused blood component did not differ between the intraoperative bleeding and traumatic bleeding scenarios.

Association between the severity of hearing loss and the risk of dementia within the 2010-2017 national insurance service survey in South Korea.

Hearing loss and dementia are highly prevalent neurologic conditions in older adults that can considerably impact the quality of life and create social and familial burdens. To investigate the impact of hearing loss on the risk of developing dementia in a nationwide long-term follow-up study using data obtained from the South Korean National Health Information Database. Retrospective medical data for patients of all ages were extracted from the database between January 2010 and December 2017. According to the national disability registry, the degree of severe-profound hearing loss is classified into six grades. We categorized hearing loss into three groups based on the disability registry severity: (1) severe hearing disability (HD), defined as 1st to 3rd grade disabling hearing loss; (2) non-severe HD, 4th and 5th grade disabling hearing loss; and (3) ipsilateral HD, 6th grade disabling hearing loss. After adjusting for potential confounding variables, the hazard ratio (HR) for all dementia types was 1.336 (95% CI 1.306-1.367) in the severe HD group, 1.312 (95% CI 1.286-1.338) in the non-severe HD group, and 1.257 (95% CI 1.217-1.299) in the ipsilateral HD group. On assessing by the age group, the risk of all dementia types in patients younger than 65 years was as follows: HR 1.933 (95% CI 1.779-2.101), 1.880 (95% CI 1.732-2.041), and 1.601 (95% CI 1.435-1.787) in the severe, non-severe, and ipsilateral HD groups, respectively. This study demonstrates that the impact of hearing loss on dementia incidence is severity-dependent, and the risk increases in patients younger than 65 years of age.

Visual Scene-Aware Hybrid and Multi-Modal Feature Aggregation for Facial Expression Recognition.

Facial expression recognition (FER) technology has made considerable progress with the rapid development of deep learning. However, conventional FER techniques are mainly designed and trained for videos that are artificially acquired in a limited environment, so they may not operate robustly on videos acquired in a wild environment suffering from varying illuminations and head poses. In order to solve this problem and improve the ultimate performance of FER, this paper proposes a new architecture that extends a state-of-the-art FER scheme and a multi-modal neural network that can effectively fuse image and landmark information. To this end, we propose three methods. To maximize the performance of the recurrent neural network (RNN) in the previous scheme, we first propose a frame substitution module that replaces the latent features of less important frames with those of important frames based on inter-frame correlation. Second, we propose a method for extracting facial landmark features based on the correlation between frames. Third, we propose a new multi-modal fusion method that effectively fuses video and facial landmark information at the feature level. By applying attention based on the characteristics of each modality to the features of the modality, novel fusion is achieved. Experimental results show that the proposed method provides remarkable performance, with 51.4% accuracy for the wild AFEW dataset, 98.5% accuracy for the CK+ dataset and 81.9% accuracy for the MMI dataset, outperforming the state-of-the-art networks.