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Abstract Background Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. Methods An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. Results Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. Conclusions The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with “undruggability.” Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses. Graphical Abstract The current investigation introduces an innovative conceptualization of bispecific short hairpin RNA (bs_shRNA) tailored for the equilibrated modulation of dual genes within a singular cellular context. This novel bs_shRNA was loaded into the genome of an oncolytic adenovirus to augment the therapeutic efficacy of oncolytic viral interventions via the targeted inhibition of mTOR and STAT3 pathways. In addition, the administration of BSV significantly reduced the volume of bladder cancer tumors, concomitantly facilitating an enhanced recruitment of CD8+T lymphocytes in vivo.

Abstract Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.

Plasmonic nanostructures, which exhibit notable localized surface plasmon resonance (LSPR) properties, are a promising approach for improving the efficiency of fiber‐shaped dye‐sensitized solar cells (FDSSCs) and flexible organic light‐emitting diodes (FOLEDs). Herein, novel plasmonic nanostructure is successfully synthesized via the self‐densification of gold nanoparticles (Au NPs) onto a genetically engineered M13 bacteriophage template. The synthesized Au NP‐M13 bio‐nanostructure show extraordinary gap‐plasmon effects and significantly enhanced LSPR properties compared to randomly dispersed Au NPs for both solid‐state FDSSCs (SS‐FDSSCs) and FOLEDs. Briefly, a power conversion efficiency (PCE) increment of 40.7% is recorded for the Au metallic NPs‐anchored M13 bacteriophage (Au NPs‐M13) enhanced SS‐FDSSCs; whereas an external quantum efficiency (EQE) increment of 47.2% is achieved for the Au NPs‐M13 enhanced FOLEDs.

Abstract Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N6-methyladenosine (m6A) RNA methylation is associated with organ fibrosis. We investigated m6A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m6A levels. In the UUO model, METTL3 expression and m6A levels were significantly increased. Transcriptomic and m6A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m6A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-β-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.

Abstract Background Parthanatos represents a critical molecular aspect of Parkinson's disease, wherein AIMP2 aberrantly activates PARP-1 through direct physical interaction. Although AIMP2 ought to be a therapeutic target for the disease, regrettably, it is deemed undruggable due to its non-enzymatic nature and predominant localization within the tRNA synthetase multi-complex. Instead, AIMP2 possesses an antagonistic splice variant, designated DX2, which counteracts AIMP2-induced apoptosis in the p53 or inflammatory pathway. Consequently, we examined whether DX2 competes with AIMP2 for PARP-1 activation and is therapeutically effective in Parkinson’s disease. Methods The binding affinity of AIMP2 and DX2 to PARP-1 was contrasted through immunoprecipitation. The efficacy of DX2 in neuronal cell death was assessed under 6-OHDA and H2O2 in vitro conditions. Additionally, endosomal and exosomal activity of synaptic vesicles was gauged in AIMP2 or DX2 overexpressed hippocampal primary neurons utilizing optical live imaging with VAMP-vGlut1 probes. To ascertain the role of DX2 in vivo, rotenone-induced behavioral alterations were compared between wild-type and DX2 transgenic animals. A DX2-encoding self-complementary adeno-associated virus (scAAV) was intracranially injected into 6-OHDA induced in vivo animal models, and their mobility was examined. Subsequently, the isolated brain tissues were analyzed. Results DX2 translocates into the nucleus upon ROS stress more rapidly than AIMP2. The binding affinity of DX2 to PARP-1 appeared to be more robust compared to that of AIMP2, resulting in the inhibition of PARP-1 induced neuronal cell death. DX2 transgenic animals exhibited neuroprotective behavior in rotenone-induced neuronal damage conditions. Following a single intracranial injection of AAV-DX2, both behavior and mobility were consistently ameliorated in neurodegenerative animal models induced by 6-OHDA. Conclusion AIMP2 and DX2 are proposed to engage in bidirectional regulation of parthanatos. They physically interact with PARP-1. Notably, DX2's cell survival properties manifest exclusively in the context of abnormal AIMP2 accumulation, devoid of any tumorigenic effects. This suggests that DX2 could represent a distinctive therapeutic target for addressing Parkinson's disease in patients.

Abstract Background Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells. Methods To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson’s disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector. Results This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson’s disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals. Conclusions Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Abstract This study was conducted to identify risk factors affecting overall survival (OS) and provide prognostication for patients with hepatocellular carcinoma (HCC) using nationwide big data. Between January 2008 and December 2014, 10,573 adult patients with new HCC were registered in a nationwide database. Among them, 6830 patients without missing data were analyzed to construct a prognostication system. A validation cohort of 4580 patients was obtained from a tertiary hospital. All patients were assumed to have received the best treatment. A conditional inference tree analysis was performed to establish a prognostic system. The C-index and calibration plot for 5-year survival were estimated for validation. As a result, the tumor burden (TB) grade was the most significant factor in determining OS, and the cutoff was TB3 (TB1‒3 versus TB4). The patients were ultimately divided into 13 prognosis groups. The C-indexes were 0.714 and 0.737 (95% confidence interval, 0.733–0.742) in the nationwide (derivation) and hospital (validation) cohorts, respectively. In the calibration plot, the 5-year survival of the validation cohort largely matched the 45-degree line. In conclusion, the proposed prognostication system with a simple tree structure enabled the detailed stratification of patient prognosis and visualized the strata of risk factors affecting OS.

Recent advancements in immersive virtual reality head-mounted displays allowed users to better engage with simulated graphical environments. Having the screen egocentrically stabilized in a way such that the users may freely rotate their heads to observe virtual surroundings, head-mounted displays present virtual scenarios with rich immersion. With such an enhanced degree of freedom, immersive virtual reality displays have also been integrated with electroencephalograms, which make it possible to study and utilize brain signals non-invasively, to analyze and apply their capabilities. In this review, we introduce recent progress that utilized immersive head-mounted displays along with electroencephalograms across various fields, focusing on the purposes and experimental designs of their studies. The paper also highlights the effects of using immersive virtual reality discovered through the electroencephalogram analysis and discusses existing limitations, current trends as well as future research opportunities that may hopefully act as a useful source of information for further improvement of electroencephalogram-based immersive virtual reality applications.

PURPOSEWe aimed to determine the safety and feasibility of transradial access (TRA) in bronchial artery and non-bronchial systemic artery (NBSA) embolization in patients with non-massive hemoptysis.METHODSThis retrospective study was approved by the Institutional Review Board. Among the 300 patients treated for hemoptysis with bronchial artery and NBSA embolization between April 2018 and July 2019, 19 procedures in 19 patients were conducted by TRA and were retrospectively analyzed. TRA was considered when the bronchial artery or NBSA originated from the arch vessel or its tributaries. The exclusion criteria of TRA included Barbeau C or D waveform and a radial artery diameter of less than 1.8 mm on ultrasound. TRA was also avoided in cases of the high-origin bronchial artery (i.e., T4 or higher level of the aorta). The hemoptysis-free time was estimated using the Kaplan–Meier method.RESULTSThe technical success (i.e., embolization of all target artery with TRA) rate was 94.7% (18 out of 19 patients). In terms of the target arteries, embolization with TRA was technically successful in treating 47 out of 48 arteries (97.9%). The 1-month and 6-month hemoptysis-free rates were 89.5% (17/19) and 73.7% (14/19), respectively. The only adverse event was iatrogenic dissection of the bronchial artery with little clinical significance in 1 patient. No access site complications were identified on post-procedure day 1 ultrasonography.CONCLUSIONWith proper patient selection, TRA offers a safe and effective approach to embolize the bronchial arteries and NBSAs in patients with hemoptysis.

Transarterial radioembolization (TARE) with yttrium 90 (90Y) has been used in the management of hepatocellular carcinoma (HCC) for more than 10 years in Korea. There are two types of 90Y radioactive microspheres available, namely, glass and resin microspheres, with comparable clinical outcomes. In general, TARE outperforms transarterial chemoembolization regarding post-embolization syndrome, time to progression, tumor downsizing for liver transplantation, and hospitalization stay. Although TARE is commonly recommended for patients with unresectable large HCCs, it can be an alternative to or performed in combination with ablation, surgical resection, and systemic treatment. This review aimed to address 90Y radioactive microspheres, patient selection, clinical outcomes, simulation tests, radioembolization procedures, follow-up imaging, and complications.

Abstract To determine the value of susceptibility-weighted imaging (SWI) for collateral estimation and for predicting functional outcomes after acute ischemic stroke. To identify independent predictors of favorable functional outcomes, age, sex, risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline diffusion-weighted imaging (DWI) lesion volume, site of steno-occlusion, SWI collateral grade, mode of treatment, and successful reperfusion were evaluated by multiple logistic regression analyses. A total of 152 participants were evaluated. A younger age (adjusted odds ratio (aOR), 0.42; 95% confidence interval (CI) 0.34 to 0.77; P

Abstract Microfluidics offers promising methods for aligning cells in physiologically relevant configurations to recapitulate human organ functionality. Specifically, microstructures within microfluidic devices facilitate 3D cell culture by guiding hydrogel precursors containing cells. Conventional approaches utilize capillary forces of hydrogel precursors to guide fluid flow into desired areas of high wettability. These methods, however, require complicated fabrication processes and subtle loading protocols, thus limiting device throughput and experimental yield. Here, we present a swift and robust hydrogel patterning technique for 3D cell culture, where preloaded hydrogel solution in a microfluidic device is aspirated while only leaving a portion of the solution in desired channels. The device is designed such that differing critical capillary pressure conditions are established over the interfaces of the loaded hydrogel solution, which leads to controlled removal of the solution during aspiration. A proposed theoretical model of capillary pressure conditions provides physical insights to inform generalized design rules for device structures. We demonstrate formation of multiple, discontinuous hollow channels with a single aspiration. Then we test vasculogenic capacity of various cell types using a microfluidic device obtained by our technique to illustrate its capabilities as a viable micro-manufacturing scheme for high-throughput cellular co-culture.

BackgroundA diverse clinical course after the spontaneous rupture of hepatocellular carcinoma (HCC) renders nonstandardized treatment protocols.PurposeTo evaluate clinical course and role of transcatheter arterial embolization (TAE) in patients with rupture of HCC.Materials and methodsThis retrospective study included 127 patients who were treated for ruptured HCC at single institution between 2005 and 2014. After multidisciplinary discussion, patients underwent medical management, TAE, emergency surgery or staged surgery. Patients were retrospectively divided into two groups based on the intent of treatment: curative and palliative. The rebleeding rate and 1-month and overall survival (OS) were compared between two groups. The incidence and survival of patients with intraperitoneal drop metastasis (IPDM) were also analyzed.ResultsThe overall rebleeding rate in patients who underwent TAE was 3.1% (3/96). One-month mortality rate was 6.3% (8/127). The rebleeding and 1-month mortality rates were not significantly different between two groups. OS was significantly higher in the curative treatment group (median: 12.0 vs 2.2 months, p

ObjectiveTo show the effective and successful technical approach of percutaneous embolization for persistent urine leakage that occurred after orthotopic neobladder formation.Materials and MethodsWe retrospectively reviewed patients who underwent percutaneous embolization of N-butyl cyanoacrylate (NBCA) and lipiodol mixture after orthotopic neobladder formation at the Seoul National University Hospital (Seoul, Korea) from 1 January 2018 to 31 December 2020.ResultsAmong total of 182 patients of neobladder formation, five patients (four males and one female) were enrolled in this study, and their median age was 61.0 years (interquartile range (IQR): 42.5–69.5 years). All the patients showed persistent urine leakage at the neobladder-urethral anastomosis site and percutaneous drainage was primarily performed. The median time to perform percutaneous embolization was 40 days (IQR: 31.5–71.5 days) postoperatively. Elective two-staged embolization was performed in three cases for large diameter with a large fluid-filled cavity, while re-embolization was needed for delayed recurrence of urine leakage in two cases. Complete resolution of urine leakage was seen in all the cases and the median time to leakage closure was 55 days (IQR: 27.5–82.5 days). The median follow-up period after leakage closure was 26 months (IQR: 15.5–36.4 months), and embolization material-related bladder stone was a noticeable complication (two cases) during follow-up, which was removed endoscopically within 1 year after embolization. All patients' quality of life (EQ-5D-5L score) was well-maintained during the entire period.ConclusionsPersistent urine leakage after neobladder formation can be effectively managed with percutaneous embolization of “dumbbell technique” by reinforcing the closure of leakage tract from inner opening to the outer opening even for large diameter (>1 cm).

Abstract This study aimed to investigate the incidence of mastoid effusion on temporal bone magnetic resonance imaging (MRI) in patients with Bell’s palsy (BP) and Ramsay Hunt syndrome (RHS), and evaluate the usefulness of mastoid effusion in early differential diagnosis between BP and RHS. The incidence of mastoid effusion on 3.0 T—temporal bone MRI, which was conducted within 10 days after the onset of acute facial nerve palsy, was compared between 131 patients with BP and 33 patients with RHS. Findings of mastoid cavity on temporal bone MRI were classified into three groups as normal mastoid, mastoid effusion, and sclerotic change, and the incidence of ipsilesional mastoid effusion was significantly higher in RHS than BP (P

Decisions of the design speed, MCR, and engine capacity have been empirically made by assuming the value termed the sea margin. Due to ambiguity regarding the effect of some factors on the sea margin, the value has been commonly decided based on experience. To evaluate the value from a new viewpoint, it is necessary to construct an approach to estimate the sea margin through an objective procedure based on a physical and mathematical model.In this paper, a framework to estimate the actual sea margin of an LNGC based on the maneuvering equations of motion is suggested by considering the hull, propeller, rudder, and given sea route under wind and waves. The fouling effect is additionally quantified as the increase of total resistance by considering the re-docking period. The operation data is reviewed to amend the increase of the total resistance considering the speed loss of a ship. Finally, the factor of how much the resistance increases due to fouling is newly obtained for the vessel. Based on the comparison of the estimated sea margin with the empirical range of the sea margin, the constructed framework is regarded as feasible.

Herpes zoster oticus (HZO) is characterized by otalgia and erythematous vesicles in the auricle or external auditory canal. Ramsay Hunt syndrome (RHS) can be diagnosed when facial nerve palsy is accompanied by these symptoms of HZO, and in this case, audio-vestibular symptoms such as hearing loss or dizziness often develop. Recently, 3D-fluid-attenuated inversion recovery sequence (3D-FLAIR) magnetic resonance imaging (MRI) has been introduced in order to evaluate the inner ear structure pathology. The purpose of this study was to investigate the audio-vestibular characteristics in correlation with temporal bone MRI findings in HZO patients. From September 2018 to June 2022, 18 patients with HZO participated in the study. Thirteen patients (77%) showed high-signal intensity in the inner ear structures in 4 h post-contrast 3D-FLAIR images. In a bithermal caloric test, the lateral semicircular canal showed high signal intensity in 4 h post-contrast 3D-FLAIR images in 75% of patients with abnormal canal paresis. While the cochlea showed high signal intensity in 4 h post-contrast 3D-FLAIR images in 75% of patients with hearing loss, the vestibulo-cochlear nerve showed enhancement in post-contrast T1-weighted images in only 33% of patients with hearing loss. The present study demonstrates that audio-vestibular deficits are well-correlated with increased signal intensity of the inner ear endorgans in 4 h post contrast 3D-FLAIR MRI.

Objective To investigate the ability of kobusone to reduce high glucose levels and promote β-cell proliferation. Methods Four-week-old female db/db mice were assigned to the kobusone (25 mg/kg body weight, intraperitoneally twice a day) or control group (same volume of PBS). Glucose levels and body weight were measured twice a week. After 6 weeks, intraperitoneal glucose tolerance tests and immunohistochemical studies were performed, and insulin levels were determined. The expression of mRNAs involved in cell proliferation, such as PI3K, Akt, cyclin D3 and p57 Kip 2 , was measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results Kobusone reduced blood glucose levels after 3 weeks and more strongly increased serum insulin levels than the vehicle. Immunohistochemistry illustrated that kobusone increased 5-bromo-2′-deoxyuridine incorporation into islet β-cells, suggesting that it can stimulate islet β-cell replication in vivo . RT-qPCR indicated that kobusone upregulated the mRNA expression of PI3K, Akt, and cyclin D3 and downregulated that of p57 Kip2 . Conclusion Our findings suggest that kobusone is a potent pancreatic islet β-cell inducer that has the potential to be developed as an anti-diabetic agent.

Fiber-shaped dye-sensitized solar cells (FDSSCs) with flexibility, weavablity, and wearability have attracted intense scientific interest and development in recent years due to their low cost, simple fabrication, and environmentally friendly operation. Since the Grätzel group used the organic radical 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as the redox system in dye-sensitized solar cells (DSSCs) in 2008, TEMPO has been utilized as an electrolyte to further improve power conversion efficiency (PCE) of solar cells. Hence, the TEMPO with high catalyst oxidant characteristics was developed as a hybrid solid-state electrolyte having high conductivity and stability structure by being integrated with a lithium bis(trifluoromethanesulfonyl)imide (Li-TFSI) film for FDSSCs. The optimized 4-Oxo TEMPO (OX) based solid-state FDSSC (SS-FDSSC) showed the PCE of up to 6%, which was improved by 34.2% compared to that of the reference device with 4.47%. The OX-enhanced SS-FDSSCs reduced a series resistance (Rs) resulting in effective electron extraction with improved short-circuit current density (JSC), while increasing a shunt resistance (Rsh) to prevent the recombination of photo-excited electrons. The result is an improvement in a fill factor (FF) and consequently a higher value for the PCE.

A 75-year-old patient complained of mastication-induced clicking tinnitus on the left side, and otoendoscopic examination revealed that the left tympanic membraneTM was outwardly bulged by clenching her teeth. Temporal bone computed tomography demonstrated that the posteromedial bony wall of the glenoid was partially dehiscent, allowing herniation of soft tissue contents of temporomandibular joint into the middle ear. Increased middle ear pressure due to soft tissue herniation can induce left tympanic membrane bulging and accompanying clicking tinnitus. Herniation of temporomandibular joint soft tissue into the middle ear should be considered as a differential diagnosis when clicking tinnitus is evoked by mastication. Keywords: Tinnitus, Mastication, Temporomandibular joint, Middle ear, Foramen of Huschke

Background The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. Methods Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. Results Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. Conclusions The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.

An uninterruptible power supply (UPS) is a device that can continuously supply power for a certain period when a power outage occurs. UPS devices are used by national institutions, hospitals, and servers, and are located in numerous public places that require continuous power. However, maintaining such devices in good condition requires periodic maintenance at specific time points. Efficient monitoring can currently be achieved using a battery management system (BMS). However, most BMSs are administrator-centered. If the administrator is not careful, it becomes difficult to accurately grasp the data trend of each battery cell, which in turn can lead to a leakage or heat explosion of the cell. In this study, a deep-learning-based intelligent model that can predict battery life, known as the state of health (SoH), is investigated for the efficient operation of a BMS applied to a lithium-based UPS device.

Aging is a multifactorial process that involves numerous genetic changes, so identifying anti-aging agents is quite challenging. Age-associated genetic factors must be better understood to search appropriately for anti-aging agents. We utilized an aging-related gene expression pattern-trained machine learning system that can implement reversible changes in aging by linking combinatory drugs. In silico gene expression pattern-based drug repositioning strategies, such as connectivity map, have been developed as a method for unique drug discovery. However, these strategies have limitations such as lists that differ for input and drug-inducing genes or constraints to compare experimental cell lines to target diseases. To address this issue and improve the prediction success rate, we modified the original version of expression profiles with a stepwise-filtered method. We utilized a machine learning system called deep-neural network (DNN). Here we report that combinational drug pairs using differential expressed genes (DEG) had a more enhanced anti-aging effect compared with single independent treatments on leukemia cells. This study shows potential drug combinations to retard the effects of aging with higher efficacy using innovative machine learning techniques.

Background: NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2), which is upregulated by a variety of neurodegenerative factors, is neuroprotective and capable of reducing detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. The purpose of this study was to investigate NOX2 expression and the degree of functional recovery following different types of facial nerve injury and assess the effects of antioxidant intervention on nerve regeneration. Methods: A total of 40 mature (6-week-old) male Sprague-Dawley (SD) rats were used. After inducing facial injury (compression injury or cutting injury), we randomized rats into four groups: A, crushing injury only; B, crushing injury with alpha lipoic acid (ALA); C, axotomy only; and D, axotomy with ALA. Recovery from facial nerve injury was evaluated 4 and 14 days after injury by performing behavioral assessments (observational scale of vibrissae movement, modified scale of eye closing and blinking reflex) and measuring changes in NOX2 experimental/control ratio in the injured (left, experimental) facial nerve relative to that in the uninjured (right, control) facial nerve. Results: A comparison between groups according to the type of injury showed a higher NOX2 expression ratio in the axotomy group than in the crushing group (p < 0.001). Regardless of injury type, both groups that received an injection of ALA exhibited a trend toward a higher NOX2 expression ratio, although this difference reached statistical significance only in the axotomy group (p < 0.001). In behavioral assessments, overall behavioral test scores were significantly higher in the crushing injury group immediately after the injury compared with that in the axotomy group. Additionally, in behavioral tests conducted 4 days after the crushing injury, the group injected with ALA showed better results than the group without injection of ALA (p = 0.031). Conclusions: Our study showed that NOX2 expression trended higher with facial nerve injury, exhibiting a significant increase with cutting-type injury. Furthermore, intraperitoneally injection with ALA may be an efficient strategy for accelerating peripheral facial nerve recovery after a crushing injury.

Abstract Distant metastasis is initiated by circulating tumor cells (CTCs), which are considered to be a determining factor for the degree of metastasis and the survival of cancer patients. Although CTC-based diagnostic approaches are being rapidly developed, limited studies have proven the benefits of CTC elimination, with most studies providing only hypothetical inference because of the technical difficulty in examining the effects of CTC elimination in vivo. We modified photodynamic therapy to specifically eliminate green fluorescent protein (GFP)-expressing CTCs and evaluated the therapeutic efficacy of CTC elimination. When circulating blood is illuminated with a blue laser (λ = 473 nm), the combination of GFP and photosensitizers induces a selective elimination of GFP-expressing CTCs, with limited effect on normal cells. In GFP-expressing cancer cell-infused or transplanted mice models, the treatment suppressed distant metastasis and extended the survival of the tumor-bearing mice. Taken together, CTCs are a core seed to be metastasized into secondary organs and elimination of CTCs may improve the survival of cancer patients.

Doxorubicin (DOX)-loaded, hyaluronic acid-ceramide (HACE) nanoassembly-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were developed for transarterial chemoembolization (TACE) therapy of liver cancer. DOX/HACE MSs with a mean diameter of 27 μm and a spherical shape were prepared based on the modified emulsification method. Their in vitro biodegradability in artificial biological fluids was observed. A more sustained drug release pattern was observed from DOX/HACE MS than from DOX MS at pH 7.4. The cellular internalization efficiency of DOX of the DOX/HACE MS group was higher than that of the DOX MS group in liver cancer cells (HepG2 and McA-RH7777 cells), mainly due to CD44 receptor-mediated endocytosis of the released DOX/HACE nanoassembly. In both HepG2 and McA-RH7777 cells, the antiproliferation and apoptotic potentials of the DOX/HACE MS were significantly higher than those of the DOX MS (p

Fiber-shaped solar cells (FSCs) with flexibility, wearability, and wearability have emerged as a topic of intensive interest and development in recent years. Although the development of this material is still in its early stages, bacteriophage-metallic nanostructures, which exhibit prominent localized surface plasmon resonance (LSPR) properties, are one such material that has been utilized to further improve the power conversion efficiency (PCE) of solar cells. This study confirmed that fiber-shaped dye-sensitized solar cells (FDSSCs) enhanced by silver nanoparticles-embedded M13 bacteriophage (Ag@M13) can be developed as solar cell devices with better PCE than the solar cells without them. The PCE of FDSSCs was improved by adding the Ag@M13 into an iodine species (I−/I3−) based electrolyte, which is used for redox couple reactions. The optimized Ag@M13 enhanced FDSSC showed a PCE of up to 5.80%, which was improved by 16.7% compared to that of the reference device with 4.97%.

Background/Aims: Recently, the eradication rate of Helicobacter pylori (H. pylori) infection has decreased to less than 80% worldwide with the use of clarithromycin-based triple therapy owing to the increased resistance of H. pylori to antibiotics, especially clarithromycin and metronidazole. This prospective study aimed to determine eradication rate of H. pylori following high and frequent doses of extended-release dexlansoprazole and amoxicillin, as a dual therapy in a region with high clarithromycin resistance rate. Methods: A total of 50 treatment-naïve patients with active H. pylori infections, who were confirmed through via rapid urease test or histology and serology between November 2015 and February 2016 at our hospital, were included for analysis. All enrolled patients were treated with 750 mg amoxicillin and 30 mg dexlansoprazole, four times a day for a total duration of 14 days. Treatment success was determined using urea breath test four weeks after treatment completion. Results: Seven out of the 50 patients (29 men and 21 women; mean age, 57 years) dropped out during the study. The total eradication rate was 52% (26/50), and that for those with a compliance rate of over 90% was 68.4% (26/38). H. pylori infections were not successfully eradicated in patients with a compliance rate of less than 90%. Nine patients (18%) reported side effects, such as mild diarrhea and abdominal fullness. No significant factors, such as smoking and alcohol consumption, affected the infection the eradication rate. Conclusions: High and frequent doses of proton pump inhibitor–amoxicillin dual therapy were not effective in eradicating H. pylori infection in a province with high clarithromycin resistance rate.

The use of tissue adhesives for the closure of wounds is of growing interest for surgery and trauma management. Here, the authors develop an adhesive that is biocompatible, enables tissue adhesion and also permits real-time imaging due to the presence of contrast agents for multiple modalities.

Abstract Sorafenib (SOF; an angiogenesis inhibitor) and 2,3,5-triiodobenzoic acid (TIBA; a contrast agent for computed tomography imaging)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated. Embolization, drug delivery, and tracing the distribution of MSs for liver cancer therapy were accomplished with the developed MSs after their intra-arterial (IA) administration. SOF/TIBA/PLGA MSs with 24.8–28.5 µm mean diameters were prepared, and the sustained release of SOF from MSs was observed. Lower systemic exposure (represented as the area under the curve [AUC]) and maximum drug concentration in plasma (Cmax) values of the SOF/TIBA/PLGA MSs group (IA administration, 1 mg/kg) in the results of the pharmacokinetic study imply alleviated unwanted systemic effects (e.g., hand and foot syndrome), compared to the SOF solution group (oral administration, 10 mg/kg). In a rat hepatoma model, the increase of microvessel density (MVD) following arterial embolization (i.e., reactive angiogenesis) was partially limited by SOF/TIBA/PLGA MSs. This resulted in the SOF/TIBA/PLGA MSs group (IA administration, single dosing, 1 mg/kg) showing a smaller tumor size increase and viable tumor portion compared to the TIBA/PLGA MSs group. These findings suggest that a developed SOF/TIBA/PLGA MS can be a promising therapeutic system for liver cancer using a transarterial embolization strategy.

This special report aimed to document our experiences in implementing the Central Imaging Archiving and Management System (CIAMS) for a multicenter clinical trial, Low-dose CT for Appendicitis Trial (LOCAT), supported by the Korean Society of Radiology and Radiology Imaging Network of Korea for Clinical Research. LOCAT was a randomized controlled trial to determine whether low-dose CT is non-inferior to standard-dose CT with respect to the negative appendectomy rate in patients aged from 15 to 44 years. Site investigators downloaded the CT images from the site picture archiving and communication system servers, and uploaded the anonymized images to the primary server. CIAMS administrators inspected the images routed to the secondary server by a cross-check against image submission worksheets provided by the site investigators. The secondary server was automatically synchronized to the tertiary backup server. Up to June 2016, 2715 patients from 20 sites participated in LOCAT for 30 months. A total of 2539 patients' images (93.5%, 2539/2715) were uploaded to the primary server, 2193 patients' worksheets (80.8%, 2193/2715) were submitted, and 2163 patients' data (79.7%, 2163/2715) were finally monitored. No data error occurred.

Ultra-thin and large-area silicon wafers with a thickness in the range of 20–70 μm, were produced by spalling using a nickel stressor layer. A new equation for predicting the thickness of the spalled silicon was derived from the Suo–Hutchinson mechanical model and the kinking mechanism. To confirm the reliability of the new equation, the proportional factor of stress induced by the nickel on the silicon wafer, was calculated. The calculated proportional factor of λ = 0.99 indicates that the thickness of the spalled silicon wafer is proportional to that of the nickel layer. A similar relationship was observed in the experimental data obtained in this study. In addition, the thickness of the stressor layer was converted to a value of stress as a guide when using other deposition conditions and materials. A silicon wafer with a predicted thickness of 50 μm was exfoliated for further analysis. In order to spall a large-area (150 × 150 mm2 or 6 × 6 in2) silicon wafer without kerf loss, initial cracks were formed by a laser pretreatment at a proper depth (50 μm) inside the exfoliated silicon wafer, which reduced the area of edge slope (kerf loss) from 33 to 3 mm2. The variations in thickness of the spalled wafer remained under 4%. Moreover, we checked the probability of degradation of the spalled wafers by using them to fabricate solar cells; the efficiency and ideality factor of the spalled silicon wafers were found to be 14.23%and 1.35, respectively.

Cost-effective, abundant, and non-toxic SnS nanosheet semiconductors can be used as water-splitting cells. Herein, a photoanode based on high-purity and highly crystalline SnS nanosheets was fabricated. We used sodium thiosulfate (Na2S2O3·5H2O) and stannous chloride (SnCl2·2H2O) as the tin and sulfur source materials, in place of SnCl4 and H2S gas, respectively, which have been used in previous studies. This gas-free fabrication process represents a new, environment-friendly fabrication method that can reduce the manufacturing cost of SnS nanosheets. The fabricated samples were characterized via X-ray diffraction, ultraviolet-visible spectroscopy, XPS, scanning electron microscopy, and Raman analyses. The XPS result indicated no Sn0 or Sn4+ in the S3 nanosheet; the nanosheet was SnS. These results with XRD show that the SnS nanosheet has high phase purity and crystallinity. Its direct optical band gap is 1.31 eV, and its lattice parameters are similar to those of standard SnS. The SnS nanosheet-based photoanode exhibited a maximum saturation photocurrent of 6.86 mA cm−2 at 0.57 V versus Ag/AgCl, with high stability. The most effective photocurrent for the photocatalytic water-splitting cell is attained with an increase in the surface area and developed electrical conduction. This is attributed to thermal annealing, which eliminates nanoparticle imperfections. This study confirms that SnS nanosheets are excellent candidates for water-splitting applications.

This paper presents a hybrid intelligent control method that enables frequency support control for permanent magnet synchronous generators (PMSGs) wind turbines. The proposed method for a wind energy conversion system (WECS) is designed to have PMSG modeling and full-scale back-to-back insulated-gate bipolar transistor (IGBT) converters comprising the machine and grid side. The controller of the machine side converter (MSC) and the grid side converter (GSC) are designed to achieve maximum power point tracking (MPPT) based on an improved hill climb searching (IHCS) control algorithm and de-loaded (DL) operation to obtain a power margin. Along with this comprehensive control of maximum power tracking mode based on the IHCS, a method for kinetic energy (KE) discharge control of the supporting primary frequency control scheme with DL operation is developed to regulate the short-term frequency response and maintain reliable operation of the power system. The effectiveness of the hybrid intelligent control method is verified by a numerical simulation in PSCAD/EMTDC. Simulation results show that the proposed approach can improve the frequency regulation capability in the power system.

We determine the influence of substitutional defects on perovskite quantum dots through experimental and theoretical investigations. Substitutional defects were introduced by trivalent dopants (In, Sb, and Bi) in CsPbBr3 by ligand-assisted reprecipitation. We show that the photoluminescence (PL) emission peak shifts toward shorter wavelengths when doping concentrations are increased. Trivalent metal-doped CsPbBr3 enhanced the PL quantum yield (~10%) and air stability (over 10 days). Our findings provide new insights into the influence of substitutional defects on substituted CsPbBr3 that underpin their physical properties.

Targeting cancer stem cells (CSCs) without damaging normal stem cells could contribute to the development of novel radical cancer therapies. Cells expressing leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) constitute a cancer-causing population in the colon; therefore, targeting of Lgr5+ cells is expected to provide an opportunity to mitigate colon cancer. However, the expression of Lgr5 in normal stem cells makes it difficult to prove the efficacy of therapies targeted exclusively at Lgr5+ cancer cells. We used a modified photodynamic therapy technique involving cellular radiative transfer between green fluorescent protein (GFP)-expressing cells and a rose bengal photosensitizer. After treatment, tumors containing GFP-Lgr5+ cells were observed to be significantly suppressed or retarded with little effect on GFP-Lgr5+ stem cells at the crypt bottom. Lgr5+ CSCs were specifically eradicated in situ, when localized based on the depth from the colon lumen, revealing the potential preventive efficacy of Lgr5-targeted therapy on tumor growth. This study supports the idea that Lgr5+ cells localized near the colon luminal surface are central to colorectal cancer. With further development, the targeting of localized Lgr5+ cancer stem cells, which this study demonstrates in concept, may be feasible for prevention of colon cancer in high-risk populations.

Emerging evidence suggests that diabetes mellitus (DM) is associated with iron and calcium metabolism. However, few studies have investigated the presence of DM in cognitively impaired patients and its effect on brain iron and calcium accumulation. Therefore, we assessed the effects of DM on cognitively impaired patients using quantitative susceptibility mapping (QSM). From June 2012 to Feb 2014, 92 eligible cognitively impaired patients underwent 3T magnetic resonance imaging (MRI). There were 46 patients with DM (DM+) and 46 aged matched patients without DM (DM-). QSM was obtained from gradient echo data and analyzed by drawing regions of interest around relevant anatomical structures. Clinical factors and vascular pathology were also evaluated. Measurement differences between DM+ and DM- patients were assessed by t tests. A multiple regression analysis was performed to identify independent predictors of magnetic susceptibility. DM+ patients showed lower susceptibility values, indicative of lower brain iron content, than DM- patients, which was significant in the hippocampus (4.80 ± 8.31 ppb versus 0.22 ± 10.60 ppb, p = 0.024) and pulvinar of the thalamus (36.30 ± 19.88 ppb versus 45.90 ± 20.02 ppb, p = 0.023). On multiple regression analysis, microbleed number was a predictor of susceptibility change in the hippocampus (F = 4.291, beta = 0.236, p = 0.042) and DM was a predictor of susceptibility change in the pulvinar of the thalamus (F = 4.900, beta = - 0.251, p = 0.030). In cognitively impaired patients, presence of DM was associated with lower susceptibility change in the pulvinar of the thalamus and hippocampus. This suggests that there may be region-specific alterations of calcium deposition in cognitively impaired subjects with DM.

Although human papillomavirus (HPV) positive oral and oropharyngeal cancers have distinct epidemiologic and molecular characteristics compared to HPV-negative cancers, all patients with oral and oropharyngeal cancers received same standard regimen regardless of HPV status. For these reasons, specific regimens for patients with HPV-positive oral and oropharyngeal cancer are needed. Differentially expressed genes (DEG) between HPV-positive and HPV-negative oropharyngeal cancers were re-analyzed and categorized from public database. Then, druggable targets to HPV-positive oral and oropharyngeal cancer were identified and were validated with E6/E7, which is oncogene of HPV, transfected oral and oropharyngeal cancer cell lines and HPV infected cell lines. In DEG analysis, HPV-positive oral and oropharyngeal cancer showed distinct disease entity from HPV-negative cancers. Unlike HPV-negative oral and oropharyngeal cancer, thymidylate synthase (TS) and topoisomerase II (Topo II) were overexpressed in HPV-positive cancers. Transfection of Lenti-virus containing E6/ E7 to HPV-negative oral and oropharyngeal cancer cells induced upregulation of TS and Topo II in those cells. Although cisplatin, which is standard regimen in head and neck cancers, showed more effectiveness in HPV-negative cells, 5-FU and pemetrexed, which are TS inhibitors, or etoposide, which is Topo II inhibitors, worked more effectively in HPV-positive cells. In addition, cisplatin/etoposide and cisplatin/pemetrexed combination regimens showed synergic effects in HPV-positive cells. Pemetrexed or etoposide alone, or in combination with other chemotherapeutic agents such as cisplatin, can be used as novel substitutes in a regimen of concurrent chemoradiotherapy or a palliative regimen for HPV-positive oral and oropharyngeal cancer patients. However, a well-designed clinical trial is needed.

This study was designed to identify potential radiosensitizing (RS) agents for combined radio- and chemotherapy in a murine model of human lung carcinoma, and to evaluate the in vivo effect of the RS agents using diffusion-weighted magnetic resonance imaging (DW-MRI). Radioresistance-associated genes in A549 and H460 cells were isolated on the basis of their gene expression profiles. Celastrol was selected as a candidate RS by using connectivity mapping, and its efficacy in lung cancer radiotherapy was tested. Mice inoculated with A549 carcinoma cells were treated with single ionizing radiation (SIR), single celastrol (SC), or celastrol-combined ionizing radiation (CCIR). Changes in radiosensitization over time were assessed using DW-MRI before and at 3, 6, and 12 days after therapy initiation. The tumors were stained with hematoxylin and eosin at 6 and 12 days after therapy. The percentage change in the apparent diffusion coefficient (ADC) value in the CCIR group was significantly higher than that in the SC and SIR group on the 12th day (Mann-Whitney U-test, p = 0.05; Kruskal-Wallis test, p < 0.05). A significant correlation (Spearman's rho correlation coefficient of 0.713, p = 0.001) was observed between the mean percentage tumor necrotic area and the mean ADC values after therapy initiation. These results suggest that the novel radiosensitizing agent celastrol has therapeutic effects when combined with ionizing radiation (IR), thereby maximizing the therapeutic effect of radiation in non-small cell lung carcinoma. In addition, DW-MRI is a useful noninvasive tool to monitor the effects of RS agents by assessing cellularity changes and sequential therapeutic responses.

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method as an automated white blood cell differential count system.

Purpose: The aim of this study was to evaluate the safety and accuracy of a new portable ultrasonography-guided high-intensity focused ultrasound (USg-HIFU) system with a 3-dimensional (3D) electronic steering transducer, a simultaneous ablation and imaging module, real-time cavitation monitoring, and 3D image reconstruction algorithms. Methods: To address the accuracy of the transducer, hydrophones in a water chamber were used to assess the generation of sonic fields. An animal study was also performed in five pigs by ablating in vivo thighs by single-point sonication (n=10) or volume sonication (n=10) and ex vivo kidneys by single-point sonication (n=10). Histological and statistical analyses were performed. Results: In the hydrophone study, peak voltages were detected within 1.0 mm from the targets on the y- and z-axes and within 2.0-mm intervals along the x-axis (z-axis, direction of ultrasound propagation; y- and x-axes, perpendicular to the direction of ultrasound propagation). Twenty-nine of 30 HIFU sessions successfully created ablations at the target. The in vivo porcine thigh study showed only a small discrepancy (width, 0.5-1.1 mm; length, 3.0 mm) between the planning ultrasonograms and the pathological specimens. Inordinate thermal damage was not observed in the adjacent tissues or sonic pathways in the in vivo thigh and ex vivo kidney studies. Conclusion: Our study suggests that this new USg-HIFU system may be a safe and accurate technique for ablating soft tissues and encapsulated organs.

BackgroundMilrinone increases intracellular adenosine 3',5'-cyclic monophosphate concentration and enhances vascular relaxation. Nuclear factor-kappa B (NF-kB) plays a key role in inflammatory responses during ischemia-reperfusion (I/R) injury. We aimed to investigate the effect of milrinone on the inflammatory responses and NF-kB activation in renal I/R injury in mice.MethodsThirty C57BL/6 mice were allocated into 3 groups. In group S (n = 10), only right nephrectomy was done. In group C (n = 10), the left kidney was subjected to 30 min of ischemia after right nephrectomy. In group M (n = 10), milrinone (5 µg/kg) was administered before ischemia. After 24 hours of reperfusion, the serum creatinine was measured, kidney samples were obtained for histology, and expressions of NF-kB and proinflammatory cytokines were analyzed.ResultsIn group C, the serum creatinine concentration was markedly elevated, compared with group S. Creatinine concentration in group M was also elevated, but it was significantly lower than that in group C. Histologic evidence of renal damage was severe in group C, but it was improved in group M. In groups C and M, expression of NF-kB, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) mRNA increased significantly compared with group S (P < 0.05). But group M showed a lower expression of NF-kB, TNF-α, ICAM-1, MCP-1 and MIP-2 mRNA than group C (P < 0.05).ConclusionsMilrinone treatment attenuates the renal inflammatory response and activation of NF-kB, resulting in improvement of renal function and tissue injury.

Purpose: To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. Methods: This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. Results: CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (Ptotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P Conclusion: Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

The original article [1] contains an inadvertent omission in the Funding declaration.

We propose a novel method to pattern the charge recombination layer (CRL) with a low-temperature solution-processable ZnO layer (under 150 °C) for organic solar cell applications. Due to the optimal drying process and thermal annealing condition, ZnO sol-gel particles formed a three-Dimensional (3D) structure without using a high temperature or ramping method. The generated 3D nano-ripple pattern showed a height of around 120 nm, and a valley-to-valley distance of about 500 nm. Based on this newly developed ZnO nano-ripple patterning technique, it was possible to pattern the CRL without damaging the underneath layers in tandem structure. The use of nano-ripple patterned ZnO as the part of CRL, led to the concomitant improvement of the power conversion efficiency (PCE) of about 30%, compared with non-patterned CRL device.

BackgroundThe patient-controlled sedation (PCS) allows for rapid individualized titration of sedative drugs. Propofol has been the most widely used IV adjuvant, during the monitored anesthesia care (MAC). This study was designed to compare the sedation quality, side effect and recovery of the propofol alone, and propofol-remifentanil combination, using PCS for breast biopsy.MethodsSeventy five outpatients, undergoing breast biopsy procedures with local anesthesia, were randomly assigned to receive propofol alone (group P), propofol-25 ug/ml of remifentanil (group PR25), and propofol-50 ug/ml of remifentanil (group PR50), using PCS. Pain visual analogue scores (VAS) and digit symbol substitution test (DSST), Vital signs, bi-spectral index (BIS) and observer assessment of alertness and sedation (OAA/S) score were recorded.ResultsApply/Demand ratio in the group PR50 had a significant increase over the other groups (P < 0.05). The incidence of excessive sedation and dizziness were significantly more frequent in the group PR50 (P < 0.05). BIS and OAA/S score significantly decreased in the group PR25, PR50 at 15 min after the operation, the end of surgery (P < 0.05). At 5 min after the start of PCS, patients in the group PR25 and PR50 gave significantly less correct responses on the DSST than that of the group P (P < 0.05).ConclusionsCompared with the propofol alone, intermittent bolus injection of propofol-remifentanil mixture could be used, appropriately, for the sedation and analgesia during MAC. The group PR25 in a low dose of remifentanil has more advantages in terms of sedation and satisfaction because of the group PR50's side effects.

This study was conducted to evaluate the outcomes of multi-channel switching RFA using a separable cluster electrode in patients with HCC.From November 2011 to July 2013, 79 patients with 98 HCCs < 5 cm were enrolled and treated with RFA using a multi-channel switching radiofrequency system and a separable cluster electrode under the guidance of a real-time fusion imaging system. The primary and secondary endpoints were the 3-year local tumor progression (LTP) rate and recurrence-free survival (RFS) rate, respectively. For post hoc analyses, LTP, RFS, and major complication rates were retrospectively compared with a historical control group treated with RFA using the same radiofrequency system but with multiple internally-cooled electrodes.The technique success rate of the 98 tumors was 100%. Cumulative 1-year, 2-year, and 3-year LTP rates were 3.4%, 6.9%, and 12.4%, respectively. For patient-level data, cumulative 1-year, 2-year, and 3-year RFS rates were 83.9%, 68.6%, and 45.4%, respectively. On post hoc analyses, none of the baseline characteristics showed a significant difference between the separable cluster electrode and multiple internally-cooled electrodes group. Cumulative LTP and RFS rates of the two groups also showed no significant difference (p = 0.401 and p = 0.881, respectively). Finally, major complication rates of the separable cluster electrode group (5.0%, 4/79) and multiple internally-cooled electrodes group (5.9%, 4/74) were also comparable (p = 1.000).Switching monopolar RFA using a separable cluster electrode is a feasible and efficient technique for the treatment of HCCs smaller than 5 cm, providing comparable local tumor control to multiple internally-cooled electrodes.ClinicalTrials.gov NCT02745483.

PurposeThe in-stent signal reduction of the stented artery caused by susceptibility artifact or radiofrequency shielding artifact limited the use of time-of-flight MR angiography (TOF-MRA) as a follow-up tool after intracranial stenting. We showed the degree of an artifact according to different stent types, and optimized MR parameters for TOF-MRA in patients with intracranial stent on 3.0 T MRI.Materials and MethodsFour stents (Neuroform, Wingspan, Solitaire, and Enterprise) were placed in a vascular flow phantom and imaged by changing flip angle (FA; 20°,30°,40°,50° and 60°) and bandwidth (BW; 31, 42 and 62.5 KHz) using TOF-MRA. Source data of each image set with different FA and BW were reconstructed with the maximal intensity projection (MIP) technique, and MIP images were used to evaluate the in-stent signal reduction of each stent according to the change of MR parameters. The in-stent signal reduction was assessed by calculating the relative in-stent signal (RIS) inside the stent as compared with background and signal intensity of the tube outside the stent. The optimal FA and BW of each stent were determined by comparing the RIS in each stent by one-sample t test. Finally, one neuroradiologist chose one image set with the best image quality.ResultsThe mean RIS for Neuroform, Wingspan, Solitaire and Enterprise stent was 66.3 ± 6.0, 44.2 ± 5.8, 22.8 ± 3.3 and 8.2 ± 2.9, respectively. The significantly high RIS of each stent was obtained with FA/BW value of 20°/31 KHz (Neuroform), 20°/31 KHz and 30°/42 KHz (Wingspan), 40°/42 KHz and 50°/31 KHz (Solitaire) and 40°/31 KHz and 50°/31 KHz (Enterprise). Among these MIP images with significantly high RIS, images with FA/BW value of 20°/31 KHz (Neuroform and Wingspan) and 50°/31 KHz (Solitaire and Enterprise) had the best image quality.ConclusionThe degree of artifact was variable according to the design of each intracranial stent. The luminal visualization of closed-cell design stents such as Solitaire and Enterprise can be improved by higher FA. Thus, MR parameter should be adjusted according to the type of intracranial stents.

PurposeCerebral arterial dissections are recognized as a common cause of stroke. However, few studies have reported on the distribution of cerebral arterial dissection and angiographic pattern related to the presenting clinical symptom pattern. We analyzed the distribution of cerebral artery dissection along with angiographic and clinical presenting a pattern as depicted on angiograms.Materials and MethodsFrom January 2000 to January 2007, 133 arterial dissection patients admitted to our institutes were retrospectively reviewed. The characteristic angiographic findings of all cerebral arteries were carefully evaluated on 4-vessel angiograms. The male-female ratio was 77: 56 and the mean age was 51 years. According to the angiographic finding depicting the location of the dissection plane in the arterial wall, we categorized to steno-occlusive, aneurysmal, combined and unclassifiable pattern. In each dissection pattern, we evaluated presenting symptoms and presence of infarction or hemorrhage.ResultsThe most common symptom on presentation was headache (47%), followed by motor weakness of arm or leg (31%), dysarthria/aphasia (19%) and vertigo (16%). The most common angiographic pattern was steno-occlusive (46%), followed by combined (steno-occlusive and aneurismal) (27%) and aneurysmal (22%) patterns. Steno-occlusive pattern was most commonly related to infarction (33/61, 54%) in contrast that aneurysmal pattern was most frequently related to subarachnoid hemorrhage (SAH) (7/29, 24%). The most frequent abnormality in patients with dissection of the intradural vertebral arteries including posterior cerebral artery (PCA) was SAH (23/70, 33%), followed by infarction. Infarction was the most common abnormality in patients with the extradural and intradural carotid arteries, and the extradural vertebral artery.ConclusionIn contrast that the extradural arterial dissections tended to result in ischemia with steno-occlusive pattern, the intradural arterial dissections tended to result in SAH with aneurysmal type, especially in the vertebral artery. Dissection requires combined analysis of angiographic pattern and type of stroke depending on the location.