Paper-Based Multiplex Surface-Enhanced Raman Scattering Detection Using Polymerase Chain Reaction Probe Codification.

We construct a multiplex surface-enhanced Raman scattering (SERS) platform based on a plasmonic paper substrate and a double-labeled probe for the detection of multiple fluorescent dyes at high sensitivity in a single-wavelength light source system. Plasmonic paper, made of silver nanodots on three-dimensional cellulose fibers, enables highly sensitive SERS biosensing based on localized surface plasmon resonance (LSPR). The proposed method enables the identification and quantification of a range of fluorescent dyes ranging from picomolar to millimolar concentrations. The use of 5' fluorescent dyes and 3' biotin-modified probes as SERS-coded probes renders possible the separation of fluorescent dyes with streptavidin-coated magnetic beads (SMBs) and the sensitive detection of multiple dyes after the reverse transcription polymerase chain reaction (RT-PCR). This experimental study reveals the multiplex detection capability of PCR-based SERS under existing PCR conditions without modifying primer and probe sequences. The combination of magnetic bead-based separation and paper SERS platform is efficient, economical, and can be used for the simultaneous detection of two or more pathogens.

Baseline increased 18F-fluoride uptake lesions at vertebral corners on positron emission tomography predict new syndesmophyte development in ankylosing spondylitis: a 2-year longitudinal study.

The goal of this study was to demonstrate whether increased 18F-fluoride uptake lesions on positron emission tomography (PET) scan can predict new syndesmophyte development in patients with ankylosing spondylitis (AS). In 12 AS patients, 18F-fluoride PET and magnetic resonance imaging (MRI) was performed at baseline, and radiography was performed at baseline and the 2-year follow-up. The following data were recorded: the presence of increased 18F-fluoride uptake lesions on PET defined as an uptake greater than the uptake in the adjacent normal vertebral body; acute (type A) and advanced (type B) corner inflammatory lesions (CILs) and fat lesions on MRI; and syndesmophytes on radiography. Of 231 anterior vertebral corners without syndesmophyte at baseline, 13 type A CILs (5.5%), 2 type B CILs (0.9%), and 20 fat lesions (8.7%) on MRI and six increased fluoride uptake lesions (2.6%) on PET were observed. At the 2-year follow-up, 16 new syndesmophytes (6.9%) in eight AS patients (66.7%) occurred. New syndesmophytes developed significantly more frequently in anterior vertebral corners with increased 18F-fluoride uptake lesions (50%) or fat lesions (25%) at baseline than in those without such lesions (5.8 and 5.2%; p = 0.005 and p = 0.007, respectively). After adjusting confounding factors, baseline increased 18F-fluoride uptake lesions was independently associated with new syndesmophytes development (OR 13.8, 95% CI 1.5-124.3, p = 0.019). Fat lesions were also associated with new syndesmophytes formation. Our data suggest that 18F-fluoride PET may be applied to identify AS patients with high risk of future syndesmophyte formation.

Compliance and persistence with oral bisphosphonates for the treatment of osteoporosis in female patients with rheumatoid arthritis.

BACKGROUND: Poor adherence with oral bisphosphonates (BPs) can mitigate their therapeutic benefit for osteoporosis and is a significant clinical burden. Most previous studies regarding adherence with oral BPs have focused on postmenopausal osteoporosis, but little attention has been given to patients with rheumatoid arthritis (RA). Thus, we investigated compliance and persistence with oral BPs in the treatment of osteoporosis and analyzed risk factors for poor adherence in female patients with (RA) in real setting. METHODS: This is a retrospective longitudinal study including 396 female patients with RA in whom oral BPs were newly initiated from Aug 2004 to Aug 2014 at a university rheumatology center in South Korea. Compliance was quantified using the 1-year medication possession ratio (MPR), while persistence was defined as duration from the initiation to the end of BPs therapy without interruption exceeding 56 days. Seropositve RA was defined as having a positive test result for the presence of either rheumatoid factor or anti-cyclic citrullinated peptide antibody. RESULTS: Of 396 RA patients, 221 (55.8%) were prescribed risedronate 35 mg weekly; 17 (4.3%) received alendronate 70 mg weekly; and 158 (39.9%) received ibandronate 150 mg monthly. The 1-year MPR was 70.1% and the proportion of RA patients with the 1-year MPR ≥ 0.8 was 60.1%. A total of 274 (69.2%) patients discontinued oral BPs during the study period and persistence with BPs was 63.3% at 1 year, 50.7% at 2 years and 33.3% at 3 years. The most common cause of non-persistence was adverse events (47.5%), followed by poor health literacy (40.5%) and cost (12%). Both compliance and persistence with monthly oral BPs were significantly lower than those with weekly regimens (OR: 2.48, 95% CI: 1.59-3.89, P < 0.001 and HR: 2.19, 95% CI: 1.69-2.83, P < 0.001, respectively). Additionally, patients with seropositive RA showed better compliance and persistence with BPs compared with their seronegative counterparts. CONCLUSIONS: Compliance and persistence with oral BPs in RA patients were suboptimal in real practice, thereby limiting the efficacy of osteoporosis treatment. Extending the dosing interval of BPs may improve medication adherence in RA patients.

Insulin resistance is associated with digital ulcer in patients with systemic sclerosis.

OBJECTIVES: To investigate the relationship between insulin resistance and digital ulcers (DUs) in patients with systemic sclerosis (SSc). METHODS: Using a cross-sectional design, we recruited 73 consecutive female patients with SSc and 109 sex- and age-matched healthy controls in South Korea from July 2014 to June 2015. The magnitude of insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). DUs ever included active and healed DUs and the extent of skin fibrosis was evaluated using the modified Rodnan skin score (MRSS). RESULTS: The HOMA-IR in patients with SSc was significantly higher than that in healthy controls (median 1.18 vs. 0.71, p<0.001). In SSc patients, 7 (9.6%) had active DUs and 14 subjects (19.2%) had healed DUs; thus, DUs ever were observed in 21 cases (28.8%). SSc patients with DUs ever had significantly higher HOMA-IR and MRSS compared with those without this feature (median, 2.05 vs. 0.99, p=0.001 and 14 vs. 9.5, p=0.011, respectively). After adjustment for confounding factors using multivariable logistic regression analyses, the HOMA-IR showed a significant positive association with the presence of DUs ever in patients with SSc (OR=1.43, 95% CI=1.01-2.05, p=0.048). In addition, higher MRSS was significantly correlated with DUs ever (OR=1.11, 95% CI=1.02-1.21, p=0.015). CONCLUSIONS: Insulin resistance was independently associated with the presence of DUs in patients with SSc and may be a potential biomarker for SSc micro-vasculopathy. Moreover, our data also suggest a potential contribution of insulin resistance to the pathogenesis of DUs.

Assessment of bone synthetic activity in inflammatory lesions and syndesmophytes in patients with ankylosing spondylitis: the potential role of 18F-fluoride positron emission tomography-magnetic resonance imaging.

OBJECTIVES: 18F-fluoride uptake represents active osteoblastic bone synthesis. We assessed bone synthetic activity in inflammatory lesions and syndesmophytes in patients with ankylosing spondylitis (AS) using 18F-fluoride positron emission tomography-magnetic resonance imaging (PET-MRI, Philips Healthcare, Cleveland, OH, USA) and x-ray. METHODS: All images of 12 AS patients were recorded with the presence or absence of increased 18F-fluoride uptake lesions on PET, acute (type A) or advanced (type B) corner inflammatory lesions (CILs) on MRI, syndesmophytes on x-ray at the anterior vertebral corners. An increased 18F-fluoride uptake lesion was defined as an uptake which is greater than the uptake in the adjacent normal vertebral body. The association of a CIL or syndesmophyte with an increased 18F-fluoride uptake lesion was investigated by generalised linear latent mixed models analysis to adjust within-patient dependence for total numbers of vertebral corners. RESULTS: There were 67 type A CILs (12.1%), 37 type B CILs (6.7%) and 58 increased 18F-fluoride uptake lesion (10.4%) out of 552 vertebral corners and there were 57 syndesmophytes (19.8%) out of 288 vertebral corners. A type A CIL (OR=3.2, 95% CI=1.6-6.5, p=0.001), type B CIL (OR=59.9, 95% CI=23.5-151.5, p<0.001) and syndesmpophyte (OR=21.8, 95% CI=5.5-85.2, p<0.001) were significantly associated with an increased 18F-fluoride uptake lesion. CONCLUSIONS: Our data suggest that an inflammatory lesion as well as a syndesmophyte is associated with active bone synthesis assessed by 18F-fluoride uptake in the spine of AS patients. 18F-fluoride PET-MRI may have the potential for investigating the pathogenesis of structural damage in AS.

Carbopol-incorporated thermoreversible gel for intranasal drug delivery.

The present study describes the preparation and evaluation of a poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) for enhancing the aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD HCl). The prepared gels were characterized by gelation temperature, viscoelasticity, and drug release profile. Thermoreversibility of P407/C934P gel was demonstrated by rheological studies. The incorporation of carbopol into P407 gel also reduced the amounts of drug released from the gel formulations (p < 0.05). In vivo pharmacokinetic results of the prepared gel formulations in rabbits (at 0.5 mg/kg dose) showed that the relative bioavailability of drug from P407/C934P gel was 11.3 and 2.7-fold higher than those of drug solution and P407 gel group, respectively. These findings suggested that developed thermoreversible gels could be used as promising dosage forms to improve intranasal drug absorption.

Analysis of taVNS effects on autonomic and central nervous systems in healthy young adults based on HRV, EEG parameters.

Objective.Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method of stimulating the vagus nerve, simultaneously affects the autonomic nervous system (ANS) and central nervous system (CNS) through efferent and afferent pathways. The purpose of this study is to analyze the effect of taVNS on the ANS and CNS through heart rate variability (HRV) and electroencephalography (EEG) parameters of identified responders.Approach.Two sets of data were collected from each of 10 healthy adult male subjects in their 20 s, and five HRV parameters from the time domain (RMSSD, pNN50, pNN30, pNN20, ppNNx) and two EEG parameters (power of alpha band, power of delta band) were extracted.Main results.Based on pNN50, responders to taVNS were identified; among them, pNN50 (p= 0.0041) and ppNNx (p= 0.0037) showed significant differences before and after taVNS. At the same time, for alpha power and delta power of EEG, significant difference (p< 0.05) was observed in most channels after taVNS compared to before stimulation.Significance.This study demonstrated the validity of identifying responders using pNN50 and the influence of taVNS on both the ANS and CNS. We conclude that taVNS can be used to treat a variety of diseases and as a tool to help control the ANS and CNS.

Effects of Game-Related Tasks for the Diagnosis and Classification of Gaming Disorder.

Gaming disorder (GD) is an addictive behavior characterized by an insatiable need to play video games and shares similar symptoms with the failure of self-control due to a decline in cognitive function. Current GD diagnostic and screening tools rely on questionnaires and behavioral observations related to cognitive functions to assess an individual's capacity to maintain self-control in everyday life. However, current GD screening approaches rely on subjective symptoms, and a reliable diagnosis requires long-term clinical follow-up. Recent studies have measured biosignals along with cognitive functional tasks to provide objectivity to GD diagnosis and to acquire immediate results. However, people with GD are hypersensitive to game-related cues, so their responses may vary depending on the type of stimuli, and the difference in response to stimuli might manifest as a difference in the degree of change in the biosignal. Therefore, it is critical to choose the correct stimulus type when performing GD diagnostic tasks. In this study, we investigated the task dependence of cognitive decline in GD by comparing two cognitive functional tasks: a continuous performance task (CPT) and video game play. For this study, 69 young male adults were classified into either the gaming disorder group (GD, n = 39) or a healthy control group (HC, n = 30). CPT score, EEG signal (theta, alpha, and beta), and HRV-HF power were assessed. We observed differences in the left frontal region (LF) of the brain between the GD and HC groups during online video game play. The GD group also showed a significant difference in HF power of HRV between CPT and online video gaming. Furthermore, LF and HRV-HF significantly correlated with Young's Internet Addiction Test (Y-IAT) score, which is positively associated with impulsivity score. The amount of change in theta band activity in LF and HRV-HF-both biomarkers for changes in cognitive function-during online video game play suggests that people with GD express task-dependent cognitive decline compared with HC. Our results demonstrate the feasibility of quantifying individual self-regulation ability for gaming and underscore its importance for GD classification.

Quantitative analysis of pulse arrival time and PPG morphological features based cuffless blood pressure estimation: a comparative study between diabetic and non-diabetic groups.

Pulse arrival time (PAT) and PPG morphological features have attracted much interest in cuffless blood pressure (BP) estimation, but their effects are not clearly understood when vascular characteristics are affected by diseases such as diabetes. This work quantitatively analyzes the effect of diabetic disease on the PAT and PPG morphological features-based BP estimation. We selected 112 diabetic patients and 308 non-diabetic subjects from VitalDB, and extracted 16 features including PAT, PPG morphological features, and heart rate. BP estimation performance was statistically compared between groups using linear regression models with several feature sets, and the relative importance of each feature in the optimal feature set was extracted. As a result, the standard deviation of the error and mean absolute error of PAT-based BP estimation were significantly higher in the diabetic group than in the non-diabetic group (p < 0.01). A feature set containing PAT and PPG morphological features achieved the best performance in both groups. However, the relative importance of each feature for BP estimation differed notably between groups. The results indicate that different features are important depending on the vascular characteristics, which could help to construct different models to accommodate specific diseases.

Transcranial application of magnetic pulses for improving brain drug delivery efficiency via intranasal injection of magnetic nanoparticles.

As the blood-brain barrier (BBB) hinders efficient drug delivery to the brain, drug delivery via the intranasal pathway, bypassing the BBB, has received considerable attention. However, intranasal administration still has anatomical and physiological limitations, necessitating further solutions to enhance effectiveness. In this study, we used transcranial magnetic stimulation (TMS) on fluorescent magnetic nanoparticles (MNPs) of different sizes (50, 100, and 300 nm) to facilitate MNP's transportation and delivery to the brain parenchyma. To validate this concept, anesthetized rats were intranasally injected with the MNPs, and TMS was applied to the center of the head. As the result, a two-fold increase in brain MNP delivery was achieved using TMS compared with passive intranasal administration. In addition, histological analysis that was performed to investigate the safety revealed no gross or microscopic damages to major organs caused by the nanoparticles. While future studies should establish the delivery conditions in humans, we expect an easy clinical translation in terms of device safety, similar to the use of conventional TMS. The strategy reported herein is the first critical step towards effective drug transportation to the brain.

Wireless, Fully Implantable and Expandable Electronic System for Bidirectional Electrical Neuromodulation of the Urinary Bladder.

Current standard clinical options for patients with detrusor underactivity (DUA) or underactive bladder─the inability to release urine naturally─include the use of medications, voiding techniques, and intermittent catheterization, for which the patient inserts a tube directly into the urethra to eliminate urine. Although those are life-saving techniques, there are still unfavorable side effects, including urinary tract infection (UTI), urethritis, irritation, and discomfort. Here, we report a wireless, fully implantable, and expandable electronic complex that enables elaborate management of abnormal bladder function via seamless integrations with the urinary bladder. Such electronics can not only record multiple physiological parameters simultaneously but also provide direct electrical stimulation based on a feedback control system. Uniform distribution of multiple stimulation electrodes via mesh-type geometry realizes low-impedance characteristics, which improves voiding/urination efficiency at the desired times. In vivo evaluations using live, free-moving animal models demonstrate system-level functionality.

Frequency-dependent depression of the NTS synapse affects the temporal response of the antihypertensive effect of auricular vagus nerve stimulation (aVNS).

Objective. Auricular vagus nerve stimulation (aVNS) has recently emerged as a promising neuromodulation modality for blood pressure (BP) reduction due to its ease of use although its efficacy is still limited compared to direct baroreflex stimulation. Previous studies have also indicated that synaptic depression of nucleus tractus solitarius (NTS) in the baroreflex pathway depends on stimulus frequency. However, the nature of this frequency dependence phenomenon on antihypertensive effect has been unknown for aVNS. We aimed to investigate the antihypertensive effect of aVNS considering frequency-dependent depression characteristic in the NTS synapse. We explored NTS activation and BP reduction induced by aVNS and by direct secondary neuron stimulation (DS).Approach. Both protocols were performed with recording of NTS activation and BP response with stimulation for each frequency parameter (2, 4, 20, 50, and 80 Hz).Main results. The BP recovery time constant was significantly dependent on the frequency of DS and aVNS (DS-2 Hz: 8.17 ± 4.98; 4 Hz: 9.73 ± 6.3; 20 Hz: 6.61 ± 3.28; 50 Hz: 4.93 ± 1.65; 80 Hz: 4.00 ± 1.43,p< 0.001, Kruskal-Wallis (KW) H-test/aVNS-2 Hz: 4.02 ± 2.55; 4 Hz: 8.13 ± 4.05; 20 Hz: 6.40 ± 3.16; 50 Hz: 5.18 ± 2.37; 80 Hz: 3.13 ± 1.29,p< 0.05, KW H-test) despite no significant BP reduction at 2 Hz compared to sham groups (p> 0.05, Mann-Whitney U-test).Significance. Our observations suggest that the antihypertensive effect of aVNS is influenced by the characteristics of frequency-dependent synaptic depression in the NTS neuron in terms of the BP recovery time. These findings suggest that the antihypertensive effect of aVNS can be improved with further understanding of the neurological properties of the baroreflex associated with aVNS, which is critical to push this new modality for clinical interpretation.

A self-pressure-driven blood plasma-separation device for point-of-care diagnostics.

We aimed to develop a portable, simple-to-use, and self-pressure-driven blood plasma-separation device that can be combined with rapid diagnostic test kits. This simple, disposable, and electrical equipment-free apparatus has been designed to separate plasma from a few microliters of blood with only hand-powered operation. The refined plasma sample is then delivered to multiple lateral flow assay kits directly connected to the device for the detection of various serological markers. The required time for all steps was just 1 min. We validated the device through multifaceted experiments. The developed multifunctional device enables to perform all blood test steps of diagnostic medical examination at the point-of-care.

Multiplex Molecular Point-of-Care Test for Syndromic Infectious Diseases.

Point-of-care (POC) molecular diagnostics for clinical microbiology and virology has primarily focused on the detection of a single pathogen. More recently, it has transitioned into a comprehensive syndromic approach that employs multiplex capabilities, including the simultaneous detection of two or more pathogens. Multiplex POC tests provide higher accuracy to for actionable decisionmaking in critical care, which leads to pathogen-specific treatment and standardized usages of antibiotics that help prevent unnecessary processes. In addition, these tests can be simple enough to operate at the primary care level and in remote settings where there is no laboratory infrastructure. This review focuses on state-of-the-art multiplexed molecular point-of-care tests (POCT) for infectious diseases and efforts to overcome their limitations, especially related to inadequate throughput for the identification of syndromic diseases. We also discuss promising and imperative clinical POC approaches, as well as the possible hurdles of their practical applications as front-line diagnostic tests.

An Efficient Noninvasive Neuromodulation Modality for Overactive Bladder Using Time Interfering Current Method.

OBJECTIVE: The present study aimed to evaluate a new tibial nerve stimulation (TNS) modality, which uses interferential currents, in terms of the stimulation electric field penetration efficiency into the body and physiological effectiveness. METHODS: In silico experiments were performed to analyze the penetration efficiency of proposed interferential current therapy (ICT). Based on this, we performed in vivo experiments to measure excitation threshold of ICT for the tibial nerve, which is related to stimulation field near the nerve. Regarding analysis of the physiological effectiveness, in vivo ICT-TNS was performed, and changes in bladder contraction frequency and voiding volume were measured. The penetration efficiency and physiological effectiveness of ICT were evaluated by comparison with those of conventional TNS using transcutaneous electrical nerve stimulation (TENS). RESULTS: Simulation results showed that ICT has high penetration efficiency, thereby generating stronger field than TENS. These results are consistent with the in vivo results that nerve excitation threshold of ICT is lower than that of TENS. Moreover, ICT-TNS decreased contraction frequency and increased voiding volume, and its performance was profound compared with that of TENS-TNS. CONCLUSION: The proposed ICT is more efficient in inducing the stimulation field near the tibial nerve placed deep inside the body compared with conventional TENS and shows a good clinical effectiveness for TNS. SIGNIFICANCE: The high efficiency of ICT increases the safety of noninvasive neurostimulation; therefore, it has clinical potential to become a promising modality for TNS to treat OAB and other peripheral neurostimulations.

Biologically Safe, Degradable Self-Destruction System for On-Demand, Programmable Transient Electronics.

The lifetime of transient electronic components can be programmed via the use of encapsulation/passivation layers or of on-demand, stimuli-responsive polymers (heat, light, or chemicals), but yet most research is limited to slow dissolution rate, hazardous constituents, or byproducts, or complicated synthesis of reactants. Here we present a physicochemical destruction system with dissolvable, nontoxic materials as an efficient, multipurpose platform, where chemically produced bubbles rapidly collapse device structures and acidic molecules accelerate dissolution of functional traces. Extensive studies of composites based on biodegradable polymers (gelatin and poly(lactic-co-glycolic acid)) and harmless blowing agents (organic acid and bicarbonate salt) validate the capability for the desired system. Integration with wearable/recyclable electronic components, fast-degradable device layouts, and wireless microfluidic devices highlights potential applicability toward versatile/multifunctional transient systems. In vivo toxicity tests demonstrate biological safety of the proposed system.

Syndrome of inappropriate secretion of antidiuretic hormone as a leading cause of hyponatremia in children who underwent chemotherapy or stem cell transplantation.

BACKGROUND: Hyponatremia is a common metabolic disorder in cancer patients. However, little information is available for patients receiving chemotherapy or stem cell transplantation (SCT). We analyzed the frequency, characteristics, and various causes of hyponatremia including routine use of hypotonic fluids in children following chemotherapy or SCT. PROCEDURE: We reviewed the clinical and laboratory data of 63 children who received chemotherapy or SCT at the Department of Pediatrics, Hanyang University Medical Center from July 2005 to July 2008. RESULTS: All 63 patients at admission received routine parenteral fluids of 0.25% or 0.45% NaCl and 82 episodes of hyponatremia were observed in 40 (63.5%) patients. Of these 82 episodes, 50 episodes of hyponatremia developed in 29 children following chemotherapy and 32 episodes in 16 children following SCT. Seventy-six out of 82 episodes (92.7%) of hyponatremia developed in 37 patients receiving hypotonic fluids with NaCl concentrations between 30 and 150 mEq/L. The frequency of SIADH in the SCT setting was more frequent (14/21, 66.6%) than in the chemotherapy setting (18/58, 31.0%) (P = 0.02), even though the leading cause of hyponatremia was SIADH in both settings. CONCLUSIONS: SIADH is a leading cause of hyponatremia in children following chemotherapy or SCT, and more frequent in SCT settings than in chemotherapy settings. Furthermore, the routine use of hypotonic fluids which could aggravate the development of hyponatremia for these patients should be avoided and then switched to isotonic fluids.

The long-lasting post-stimulation inhibitory effects of bladder activity induced by posterior tibial nerve stimulation in unanesthetized rats.

Tibial nerve stimulation (TNS) is one of the neuromodulation methods used to treat an overactive bladder (OAB). However, the treatment mechanism is not accurately understood owing to significant differences in the results obtained from animal and clinical studies. Thus, this study was aimed to confirm the response of bladder activity to the different stimulation frequencies and to observe the duration of prolonged post-stimulation inhibitory effects following TNS. This study used unanesthetized rats to provide a closer approximation of the clinical setting and evaluated the changes in bladder activity in response to 30 min of TNS at different frequencies. Moreover, we observed the long-term changes of post-stimulation inhibitory effects. Our results showed that bladder response was immediately inhibited after 30 min of 10 Hz TNS, whereas it was excited at 50 Hz TNS. We also used the implantable stimulator to observe a change in duration of the prolonged post-stimulation inhibitory effects of the TNS and found large discrepancies in the time that the inhibitory effect lasted after stimulation between individual animals. This study provides important evidence that can be used to understand the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS as well as the long-lasting prolonged post-stimulation effect.

Effectiveness of electrical stimulation on nerve regeneration after crush injury: Comparison between invasive and non-invasive stimulation.

Several studies have investigated the use of invasive and non-invasive stimulation methods to enhance nerve regeneration, and varying degrees of effectiveness have been reported. However, due to the use of different parameters in these studies, a fair comparison between the effectiveness of invasive and non-invasive stimulation methods is not possible. The present study compared the effectiveness of invasive and non-invasive stimulation using similar parameters. Eighteen Sprague Dawley rats were classified into three groups: the iES group stimulated with fully implantable device, the tES group stimulated with transcutaneous electrical nerve stimulation (TENS), and the injury group (no stimulation). The iES and tES groups received stimulation for 6 weeks starting immediately after the injury. Motor function was evaluated using the sciatic functional index (SFI) every week. The SFI values increased over time in all groups; faster and superior functional recovery was observed in the iES group than in the tES group. Histological evaluation of the nerve sections and gastrocnemius muscle sections were performed every other week. The axon diameter and muscle fiber area in the iES group were larger, and the g-ratio in the iES group was closer to 0.6 than those in the tES group. To assess the cause of the difference in efficiency, a 3D rat anatomical model was used to simulate the induced electric fields in each group. A significantly higher concentration and intensity around the sciatic nerve was observed in the iES group than in the tES group. Vector field distribution showed that the field was orthogonal to the sciatic nerve spread in the tES group, whereas it was parallel in the iES group; this suggested that the tES group was less effective in nerve stimulation. The results indicated that even though rats in the TENS group showed better recovery than those in the injury group, it cannot replace direct stimulation yet because rats stimulated with the invasive method showed faster recovery and superior outcomes. This was likely attributable to the greater concentration and parallel distribution of electric field with respect to target nerve.

Expandable and implantable bioelectronic complex for analyzing and regulating real-time activity of the urinary bladder.

Underactive bladder or detrusor underactivity (DUA), that is, not being able to micturate, has received less attention with little research and remains unknown or limited on pathological causes and treatments as opposed to overactive bladder, although the syndrome may pose a risk of urinary infections or life-threatening kidney damage. Here, we present an integrated expandable electronic and optoelectronic complex that behaves as a single body with the elastic, time-dynamic urinary bladder with substantial volume changes up to ~300%. The system configuration of the electronics validated by the theoretical model allows conformal, seamless integration onto the urinary bladder without a glue or suture, enabling precise monitoring with various electrical components for real-time status and efficient optogenetic manipulation for urination at the desired time. In vivo experiments using diabetic DUA models demonstrate the possibility for practical uses of high-fidelity electronics in clinical trials associated with the bladder and other elastic organs.