Impact of various anesthetic regimens on motor-evoked potentials in infants undergoing spinal surgery: A case series.

Motor-evoked potential (MEP) monitoring is commonly used in children. MEP monitoring in infants is difficult due to smaller signals requiring higher stimulation voltages. There is limited information on the effect of different anesthetics on MEP monitoring in this age group. This case series describes the effect of different anesthetic regimens on MEP monitoring in infants. Patients <1 year of age who underwent spinal surgery with MEP monitoring between February 2022 and July 2023 at a single tertiary care children hospital were reviewed. The motor-evoked potential amplitudes were classified into 4 levels based on the voltage in the upper and lower limbs (none, responded, acceptable, sufficient). "Acceptable" or "sufficient" levels were defined as successful monitoring. A total of 19 infants were identified, involving 3 anesthesia regimens: 4/19 (21.1%) cases were anesthetized with propofol/remifentanil total intravenous anesthesia (TIVA), 3/19 (15.8%) with propofol/remifentanil/low-dose sevoflurane and another 12/19 (63.2%) cases who initially received propofol/remifentanil/sevoflurane and were converted to propofol/remifentanil anesthesia intraoperatively. The 4 cases with propofol/remifentanil showed 20/32 (62.5%) successful monitoring points. In contrast, 6/24 (25%) successful points were achieved with propofol/remifentanil intravenous anesthesia/0.5 age-adjusted minimum alveolar concentration sevoflurane. In 12 cases converted from propofol/remifentanil/low-dose inhalational anesthetics to TIVA alone, successful MEP monitoring points increased from 46/96 (47.9%) to 81/96 (84.4%). Adding low-dose inhalation anesthetic to propofol-based TIVA suppresses MEP amplitudes in infants. The optimal anesthetic regimen for infants requires further investigation.

Vibegron inhibits enhanced spontaneous contractions induced by anoxia/reoxygenation in isolated whole bladder from rats.

It has been recently proposed that repeated bladder ischemia/reperfusion induced by chronic pelvic ischemia may lead to detrusor overactivity, followed by lower urinary tract symptoms. Vibegron is a selective ß3-adrenoceptor agonist approved for the treatment of overactive bladder. Several studies have tested ß3-adrenoceptor agonists using animal models with detrusor overactivity related to bladder ischemia/reperfusion. However, whether ß3-adrenoceptor agonists directly affect ischemia/reperfusion-evoked detrusor overactivity is unclear. Therefore, we examined whether bladder anoxia/reoxygenation could enhance spontaneous bladder contractions (SBCs) and investigated the effect of vibegron on enhanced SBCs. Isolated whole bladders from rats were incubated with Krebs solution aerated with 95% N2 + 5% CO2 for 5 h (anoxia). Subsequently, the bathing solution was replaced with an oxygen-saturated solution (reoxygenation). Anoxia/reoxygenation caused enhancement of the amplitude but not the frequency of SBC compared with that before reoxygenation. Vibegron (0.3-30 µM) inhibited this increase in SBC amplitude, but not the frequency, in a dose-dependent manner. The inhibitory effect of vibegron was not affected by pretreatment with the adenylyl cyclase inhibitor SQ22536 (100 µM) or protein kinase A inhibitor KT5720 (1 µM) and was not accompanied by considerable changes in cyclic adenosine monophosphate (cAMP) content in the bladder. In contrast, the large conductance potassium channel inhibitor iberiotoxin (100 nM) suppressed the inhibitory effect of vibegron. These results suggest that bladder ischemia/reperfusion induces SBC enhancement and vibegron directly inhibits detrusor overactivity via the large conductance potassium channel, which involves ß3-adrenoceptor, rather than the cAMP signaling pathway.

An Intelligent Approach for Cloud-Fog-Edge Computing SDN-VANETs Based on Fuzzy Logic: Effect of Different Parameters on Coordination and Management of Resources.

The integration of cloud-fog-edge computing in Software-Defined Vehicular Ad hoc Networks (SDN-VANETs) brings a new paradigm that provides the needed resources for supporting a myriad of emerging applications. While an abundance of resources may offer many benefits, it also causes management problems. In this work, we propose an intelligent approach to flexibly and efficiently manage resources in these networks. The proposed approach makes use of an integrated fuzzy logic system that determines the most appropriate resources that vehicles should use when set under various circumstances. These circumstances cover the quality of the network created between the vehicles, its size and longevity, the number of available resources, and the requirements of applications. We evaluated the proposed approach by computer simulations. The results demonstrate the feasibility of the proposed approach in coordinating and managing the available SDN-VANETs resources.

A Study of Terahertz-Wave Cylindrical Super-Oscillatory Lens for Industrial Applications.

This paper describes the design and development of a cylindrical super-oscillatory lens (CSOL) for applications in the sub-terahertz frequency range, which are especially ideal for industrial inspection of films using terahertz (THz) and millimeter waves. Product inspections require high resolution (same as inspection with visible light), long working distance, and long depth of focus (DOF). However, these are difficult to achieve using conventional THz components due to diffraction limits. Here, we present a numerical approach in designing a 100 mm × 100 mm CSOL with optimum properties and performance for 0.1 THz (wavelength λ = 3 mm). Simulations show that, at a focal length of 70 mm (23.3λ), the focused beam by the optimized CSOL is a thin line with a width of 2.5 mm (0.84λ), which is 0.79 times the diffraction limit. The DOF of 10 mm (3.3λ) is longer than that of conventional lenses. The results also indicate that the generation of thin line-shaped focal beam is dominantly influenced by the outer part of the lens.

Subdiffraction focusing with a long focal length using a terahertz-wave super-oscillatory lens.

This Letter describes a super-oscillatory lens (SOL), with concentric ring-type metallic slits photolithographically fabricated on a glass substrate, that can function at subterahertz frequencies. The SOL has been investigated both experimentally and theoretically and demonstrates a spatial resolution of 1.5 mm (0.5λ), which is 0.45 times the diffraction limit, with a focal length of 75 mm (25λ) at 100 GHz (λ=3mm). Furthermore, the depth of focus of the lens was measured to be 47 mm, which is 10.8 times larger than that of a conventional lens. This type of SOL, with subdiffraction focusing, is thus highly effective for use in industrial inspections with millimeter and terahertz waves.

Performance Evaluation of an Integrated Fuzzy-Based Driving-Support System for Real-Time Risk Management in VANETs.

The highly competitive and rapidly advancing autonomous vehicle race has been on for several years now, and it has made the driver-assistance systems a shadow of their former self. Nevertheless, automated vehicles have many obstacles on the way, and until we have them on the roads, promising solutions that can be achievable in the near future should be sought-after. Driving-support technologies have proven themselves to be effective in the battle against car crashes, and with Vehicular Ad hoc Networks (VANETs) supporting them, their efficiency is expected to rise steeply. In this work, we propose and implement a driving-support system which, on the one hand, could immensely benefit from major advancement of VANETs, but on the other hand can effectively be implemented as a stand-alone system. The proposed system consists of a non-intrusive integrated fuzzy-based system able to detect a risky situation in real time and alert the driver about the danger. It makes use of the information acquired from various in-car sensors as well as from communications with other vehicles and infrastructure to evaluate the condition of the considered parameters. The parameters include factors that affect the driver's ability to drive, such as his/her current health condition and the inside environment in which he/she is driving, the vehicle speed, and factors related to the outside environment such as the weather and road condition. We show the effect of these parameters on the determination of the driving risk level through simulations and experiments and explain how these risk levels are translated into actions that can help the driver to manage certain risky situations, thus improving the driving safety.

Application of Fuzzy Logic for Selection of Actor Nodes in WSANs -Implementation of Two Fuzzy-Based Systems and a Testbed.

The development of sensor networks and the importance of smart devices in the physical world has brought attention to Wireless Sensor and Actor Networks (WSANs). They consist of a large number of static sensors and also a few other smart devices, such as different types of robots. Sensor nodes have responsibility for sensing and sending information towards an actor node any time there is an event that needs immediate intervention such as natural disasters or malicious attacks in the network. The actor node is responsible for processing and taking prompt action accordingly. But in order to select an appropriate actor to do one task, we need to consider different parameters, which make the problem NP-hard. For this reason, we consider Fuzzy Logic and propose two Fuzzy Based Simulation Systems (FBSS). FBSS1 has three input parameters such as Number of Sensors per Actor (NSA), Remaining Energy (RE) and Distance to Event (DE). On the other hand, FBSS2 has one new parameter-Transmission Range (TR)-and for this reason it is more complex. We will explain in detail the differences between these two systems. We also implement a testbed and compare simulation results with experimental results.

Short DNA Probes Developed for Sample Tracking and Quality Assurance in Gene Panel Testing.

Both multiplexing and target-enrichment technologies are key to reducing the cost of genetic testing using next-generation sequencing (NGS). Many diagnostic laboratories routinely handle thousands of targeted resequencing samples, leading to an increased risk of accidental sample mix-ups and cross contamination. Herein, we present a short DNA fragment that can be spiked into the original genomic DNA (gDNA) or whole blood sample and tracked through to the final targeted resequencing data. This DNA fragment comprises a 15-bp unique index sequence assembled with a 120-bp fixed sequence designed for recovery in a hybridization capture reaction. In a pilot study, the yield of the recovered probe was examined in a step-by-step genetic testing procedure, involving gDNA isolation from whole blood, library preparation for NGS, and capture hybridization. On the basis of the results, 10 fmol (6 × 109 molecules) and 10 amol (6 × 106 molecules) of the spike-in probe were estimated to be suitable for DNA and RNA probe-based library preparation and target enrichment from 200 ng (6.5 × 104 copies) gDNA, respectively. In fact, the number of NGS reads corresponding to the spike-in probe was almost equal to that corresponding to the genomic target regions and was sufficient for evaluating sample identification and cross-contamination events. Hence, this method may be useful for enhancing quality assurance in clinical genetic testing.

Assessing the Accuracy of Variant Detection in Cost-Effective Gene Panel Testing by Next-Generation Sequencing.

There is significant debate within the diagnostics community regarding the accuracy of variant identification by next-generation sequencing and the necessity of confirmatory testing of detected variants. Because the quality threshold to discriminate false positives depends on the workflow, no regulatory standard regarding this matter has yet been published. The goal of this study was to empirically determine the threshold to perform additional Sanger sequencing and to reduce the experimental cost to a practical level. Using 278 model genes, a hybridization capture-based protocol was examined to meet the clinical requirements of low cost, high efficiency, and high-quality data. To reduce excessive false-positive detection, filtering processes were introduced to remove mismapped reads and strand-biased detection to a published best-practices pipeline. With seven samples from the 1000 Genomes Project, 2750 single-nucleotide polymorphisms and 142 insertions/deletions were identified by our designed workflow. Compared with variants registered in the single nucleotide polymorphism database (dbSNP), a zero false-positive threshold value was determined (quality score > 1000). The variants satisfying these criteria accounted for 95.6% of single-nucleotide polymorphisms and 50.7% of insertions/deletions. Except for deletions located within the highly repeated sequences, the workflow achieved 100% sensitivity. The established threshold allowed us to discriminate between convincing variants and those requiring validation, a design that reconciles the competing objectives of cost minimization and quality maximization of clinical gene panel testing.

Generation of safe and therapeutically effective human induced pluripotent stem cell-derived hepatocyte-like cells for regenerative medicine.

Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS-HLCs for hepatocyte transplantation. First, human iPS-HLCs were generated from a human leukocyte antigen-homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder-free condition using human recombinant laminin 111, laminin 511, and type IV collagen. The percentage of asialoglycoprotein receptor 1-positive cells was greater than 80%, while the percentage of residual undifferentiated cells was approximately 0.003%. In addition, no teratoma formation was observed even at 16 weeks after human iPS-HLC transplantation. Furthermore, harmful genetic somatic single-nucleotide substitutions were not observed during the hepatocyte differentiation process. We also developed a cryopreservation protocol for hepatoblast-like cells without negatively affecting their hepatocyte differentiation potential by programming the freezing temperature. To evaluate the therapeutic potential of human iPS-HLCs, these cells (1 × 106 cells/mouse) were intrasplenically transplanted into acute liver injury mice treated with 3 mL/kg CCl4 only once and chronic liver injury mice treated with 0.6 mL/kg CCl4 twice weekly for 8 weeks. By human iPS-HLC transplantation, the survival rate of the acute liver injury mice was significantly increased and the liver fibrosis level of chronic liver injury mice was significantly decreased. Conclusion: We were able to generate safe and therapeutically effective human iPS-HLCs for hepatocyte transplantation. (Hepatology Communications 2017;1:1058-1069).

Selective photocatalytic oxidation of alcohols to aldehydes in water by TiO2 partially coated with WO3.

Semiconductor TiO(2) particles loaded with WO(3) (WO(3)/TiO(2)), synthesized by impregnation of tungstic acid followed by calcination, were used for photocatalytic oxidation of alcohols in water with molecular oxygen under irradiation at λ>350 nm. The WO(3)/TiO(2) catalysts promote selective oxidation of alcohols to aldehydes and show higher catalytic activity than pure TiO(2). In particular, a catalyst loading 7.6 wt % WO(3) led to higher aldehyde selectivity than previously reported photocatalytic systems. The high aldehyde selectivity arises because subsequent photocatalytic decomposition of the formed aldehyde is suppressed on the catalyst. The TiO(2) surface of the catalyst, which is active for oxidation, is partially coated by the WO(3) layer, which leads to a decrease in the amount of formed aldehyde adsorbed on the TiO(2) surface. This suppresses subsequent decomposition of the aldehyde on the TiO(2) surface and results in high aldehyde selectivity. The WO(3)/TiO(2) catalyst can selectively oxidize various aromatic alcohols and is reusable without loss of catalytic activity or selectivity.

One-pot synthesis of imines from alcohols and amines with TiO2 loading Pt nanoparticles under UV irradiation.

TiO(2) loading Pt nanoparticles (Pt@TiO(2)) promote one-pot synthesis of imines from alcohols and amines under UV irradiation at room temperature. This is achieved via a Pt-assisted photocatalytic oxidation of alcohols and a catalytic condensation of the formed aldehydes with amines on the TiO(2) surface.

Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery.

There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. New bidirectional chemotherapy (neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)) was developed. The aim of the present study was to assess the safety and efficacy of NIPS and to show the selection for cytoreductive surgery on PC from gastric cancer. Seventy-nine patients with PC from gastric cancer were treated with NIPS. A peritoneal port system was introduced into the abdominal cavity. The peritoneal wash cytological examination through a port was done before and after NIPS. The patients were treated with oral TS-1 twice a daily for 21 days, followed by a 1-week rest. On day 1, 8, and 15 from the start of oral TS-1 administration, 30 mg/m(2) of Docetaxel and 30 mg/m(2) of cisplatinum with 500 ml of saline were introduced into the peritoneal cavity through the port. A median course of oral TS-1 was 2.1 course and a median time of IP chemoterapy was 5.8. Peritoneal free cancer cells (PFCCs) had been detected in 65 (82.2%) patients before NIPS, and the positive cytology changed to be negative in 41 (63.0%) patients after NIPS. After NIPS, 41 patients underwent laparotomy, and complete cytoreduction was done in 32 (78%) patients. Complete cytoreduction was done in 27 (51.9%) of 52 patients with negative cytology but in only 4 (14.8%) of 27 patients with positive cytology (P < 0.001). Patients with negative cytology after NIPS survived significantly longer than those with positive cytology. The adverse effects after NIPS were mild and there was no treatment-related deaths. The grade 3/4 hematological adverse effects were found in 2 (2.6%) patients. Grade 3 renal toxicity and port site infection was found in three patients, respectively. NIPS using a port system is a safe and effective treatment for PC. Peritoneal wash cytology through a port system is a good indicator to select the patients to perform cytoreductive surgery.

Two cases of refractory Wegener's granulomatosis successfully treated with rituximab.

Conventional therapy for Wegener's granulomatosis, steroid and cyclophosphamide, fails to control disease activity in some refractory patients and has treatment-related toxicity. B cell depletion therapy using rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for certain autoimmune diseases including antineutrophil cytoplasmic antibody (ANCA) -associated systemic vasculitis. We report two refractory cases of Wegener's granulomatosis: one with bronchial and pulmonary involvement and retroorbital granuloma, the other with retroorbital granuloma and hypertrophic pachymeningitis causing severe headache. Rituximab was effective in both cases, with diminished granuloma and reduced ANCA titers, allowing steroids to be tapered. No adverse effects were detected.

Prostaglandin facilitates afferent nerve activity via EP1 receptors during urinary bladder inflammation in rats.

We examined the effects of loxoprofen, a cyclooxygenase inhibitor, and ONO-8711, an EP1-receptor antagonist, on afferent nerve activity during acetic acid (AA, 0.1% v/v)-induced inflammation of the rat urinary bladder. Distension stimulation was performed (vesical pressure of 30 cm H2O) for 2 min. The neuronal discharge was recorded from L6 dorsal root filaments. The discharge was observed just after the beginning of distension and increased gradually thereafter. When the vesical pressure returned to control value, the discharge diminished abruptly. AA infusion increased the total number of spikes to 198 +/- 38.8% of control values. AA infusion also produced asynchronous discharge in 39% of the animals. Loxoprofen administration (1 mg/kg, i.v.) reduced the number of spikes to 40.3 +/- 14.8% of control values. ONO-8711 administration (1 and 3 mg/kg, i.v.) reduced the number of spikes to 81.6 +/- 1.6% and 32.2 +/- 7.4% of control values, respectively. These data indicate that loxoprofen or EP1-receptor antagonist inhibit the inflammation-related neuronal activity. EP1 receptors in the peripheral afferent nerve terminal and/or urothelium may facilitate the primary afferent nerve activity, which elicits the inflammation-induced micturition reflex.

Design, synthesis, and evaluation of novel 2-substituted-4-aryl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-ones as NK1 antagonists.

A series of novel bicyclic pyrimidine derivatives was prepared as part of a search for NK1 antagonist aimed at the treatment of urinary incontinence. Among them, 3g, a pyrimido[4,5-b][1,5]oxazocine derivative, bearing a 4-acetylpiperazinyl group and a 2-methylphenyl group, was shown to have potent NK1 antagonist activity with a K(B) value of 0.105 nM and markedly increased the effective bladder capacity of guinea pigs (59.4% at 0.3 mg/kg iv and 62.8% at 3 mg/kg id). Furthermore, the effect of 3g on bladder function appeared to differ from that of tolterodine, another classical anti-pollakiuria agent, as determined by the distention-induced rhythmic bladder contraction assay using a urethane-anesthetized guinea pig model. Compound 3g is expected to be a promising agent for the treatment of urinary incontinence.

Design and synthesis of novel 9-substituted-7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,3-b]- and [2,3-b]-1,5-oxazocin-6-ones as NK(1) antagonists.

Novel 9-substituted-7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,3-b]- and [2,3-b]-1,5-oxazocin-6-ones were designed and prepared as part of a search for NK1 antagonists. Structure-activity relationship studies indicated that the conformational restriction resulting from the incorporation of an oxazocine ring and the presence of a terminal heteroatom on the cyclic amino group at the C-9 position play important roles in NK1, receptor recognition.

2-substituted-4-aryl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one as a structurally new NK1 antagonist.

The structurally novel pyrimido[4,5-b][1,5]oxazocine derivative 3, a hybrid compound of pyrido[4,3-b]- and [2,3-b]-1,5-oxazocine (1 and 2, respectively), was designed and synthesized. We examined the atropisomeric property and the NK1 antagonist activity of 3. Compound 3 was found to possess both a feature of 1, free rotation about the biaryl bond, and a feature of 2, potent in vivo activity.

Inhibitory effect of mizoribine on matrix metalloproteinase-1 production in synovial fibroblasts and THP-1 macrophages.

To investigate the mechanism of antirheumatic action of mizoribine (MZR), we examined the expression of matrix metalloproteinase-1 (MMP-1) and MMP-3 utilizing THP-1 derived macrophage-like cells (THP-1 macrophages) and human synovial fibroblasts (SFs). The cells were respectively stimulated with lipopolysaccharide (LPS) and interleukin-1beta in the presence or absence of MZR in vitro. The concentrations of MMP-1 and MMP-3 in the supernatant were measured by enzyme-linked immunosorbent assay. The secretion of MMP-1 from SFs, as well as THP-1 macrophages, was inhibited by MZR in a dose-dependent manner. Furthermore, a quantitative real-time polymerase chain reaction revealed that MZR decreased the expression of MMP-1 messenger RNA. These findings may be an explanation for the clinical effect of MZR in patients with rheumatoid arthritis.

Supplementation of antioxidants prevents oxidative stress during a deep saturation dive.

Conflicting views exist at the present regarding the influences of a deep saturation dive on liver function in divers. Therefore, we first reevaluated whether a deep saturation dive (400 msw) induces a hepatic disturbance. As the result, plasma activities of both transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) increased significantly, whereas cholinesterase (Ch-E) activity decreased markedly, being highly suggestive of liver dysfunction. Assuming that the liver dysfunction was attributable to oxidative stress, we next examined the effects of supplementation of antioxidants (600 mg of vitamin C, 150 mg of alpha-tocopherol, and 600 mg of tea catechins per day) on liver function in saturation divers. As was anticipated, the antioxidants taken appeared to prevent a hepatic disturbance, indicating that a deep saturation dive provokes liver dysfunction probably due to oxidative stress. Thus, we recommend that saturation divers should take supplements of antioxidants.