Search

Background: As drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity.Methods: Iodine-123- and 125-labeled 4-iodobenzylmequitazine (123/125I-BMQ) was synthesized with high labeling and purity. CYP isozymes involved in the metabolism of 125I-BMQ in mouse liver microsomes were evaluated, and the utility of 123/125I-was assessed from biological distribution and SPECT imaging evaluation in normal and CYP2D-inhibited mice.Results:In vitro metabolite analysis using mouse liver microsomes showed that 125I-BMQ is specifically metabolized by CYP2D. Biological distribution and SPECT imaging of 123/125I-BMQ in normal mice showed that injection 123/125I-BMQ accumulated early in the liver and was excreted into the gallbladder and intestines. In CYP2D-inhibited mice, accumulation in the liver was increased, but accumulation in the gallbladder and intestines, the excretory organ, was delayed. Since only metabolites of 125I-BMQ are detected in bile, visualization and measuring of the accumulation of metabolites over time in the intestine, where bile is excreted, could predict the amount of metabolites produced in the body and evaluate CYP2D activity, which would be useful in determining the dosage of various drugs metabolized by CYP2D.Conclusion:123/125I-BMQ is useful as a SPECT imaging probe for comprehensive and direct assessment of hepatic CYP2D activity in a minimally invasive and simple approach.

Objective: This study explores safety, feasibility, and potential improvement in functional status after intravenous infusion of mesenchymal stem cells (MSCs) in chronic severe brain injury (BI) patients. Methods: An intravenous infusion of autologous MSCs in autoserum cultured under Good Manufacturing Practice was delivered to four chronic patients with BI. In addition to assessing feasibility and safety, neurological function was evaluated using the National Institutes of Health Stroke Scale, Fugl-Meyer Assessment, Barthel Index, and cognitive-related behavioral assessment. Imaging studies with 18F-FDG-PETCT and 11C-methionine-PETCT (METPET) were carried out to evaluate brain metabolic activity. Results: No serious adverse events were recorded. None of the patients developed CNS tumors, abnormal cell growth, or neurological deterioration. While this initial case series was not blinded, gradual functional improvement was observed after MSC infusion. Serial 11C-METPETs displayed a statistically significant increase in methionine uptake, primarily in the thalamus and pons. Conclusion: We emphasize that this study was unblinded and did not exclude placebo effects, the contribution of endogenous recovery, or observer bias; however, our observations support feasibility and safety. No adverse events were observed. The data suggests improved quality of life after infused MSCs; however, a blinded, larger-scale study will be necessary to fully address this possibility.

Disasters disrupt lives and necessitate quick location of affected areas for rescue efforts. The application of computer vision has enhanced disaster detection, such as landslides and floods; however traditional computer vision methods often overlook smaller, critical details in favor of prominent objects. This research introduces the Retarget Network (RetNet), a novel framework aimed at improving image captioning techniques to identify and prioritize these less evident, yet crucial, objects in disaster scenarios, enhancing scene recognition and aiding in more effective disaster response. By masking images, we direct the model’s focus towards additional significant areas within the image. RetNet employs anchor boxes to refine the targeting of specific areas and, optimize their center positions, heights, and widths. Additionally, RetNet determines which anchors to mask prior to captioning, facilitating the identification of challenging objects such as boulders, soil, and water, which are indicative of natural disasters. We validated RetNet across multiple disaster scenarios—landslides, floods, and wildfires—using images taken from various perspectives, including side-view, aerial and shipborne views. Our findings reveal an accuracy of 91.60% in landslide detection from side-view image captions and 87.50% for detections from shipborne views. These results underscore RetNet’s effectiveness in enhancing the identification of disaster-affefted regions.

Near-infrared photoimmunotherapy (NIR-PIT) is a recently described method for cancer treatment that utilizes an antibody-conjugated phthalocyanine photosensitizer and NIR light. In NIR-PIT, light of 690 nm wavelength is used to activate a photosensitizer, IR700, while longer-wavelength light penetrates deeper into tissues. Thus, more effective NIR-PIT would be achieved by using photosensitizers that are activated by longer-wavelength light. The absorption wavelength would be red-shifted by destabilizing the highest occupied molecular orbital (HOMO) energy level by introducing electron donating groups at the α positions of a phthalocyanine ring. In this study, we developed a red-shifted photosensitizer for NIR-PIT, KA800, whose absorption wavelength was red-shifted by the introduction of ethoxy groups to IR700. As intended, the absorption maximum of KA800 was red-shifted compared to IR700 by 84 nm. Although phototoxicity of the antibody-KA800 (Ab-KA800) conjugate was observed in cultured cancer cells, no therapeutic effect was observed in mice. This is because the cytotoxicity of Ab-KA800 was mainly due to singlet oxygen, which can be quenched by abundant antioxidants in vivo. KA800 had low reactivity with respect to axial ligand cleavage required for inducing cell death via aggregate formation, a unique cytotoxic mechanism in NIR-PIT. The axial ligand cleavage proceeds via the anion radical formation of the photosensitizer, and KA800 was found to be less likely to receive an electron than IR700. This may be due to the destabilization of the HOMO energy level of KA800. Therefore, our findings suggest that stabilizing the lowest unoccupied molecular orbital (LUMO) energy level would be better than destabilizing the HOMO energy level for developing a red-shifted photosensitizer for NIR-PIT.

Abstract Caged compounds are frequently used in life science research. However, the light used to activate them is commonly absorbed and scattered by biological materials, limiting their use to basic research in cells or small animals. In contrast, hard X‐rays exhibit high bio‐permeability due to the difficulty of interacting with biological molecules. With the main goal of developing X‐ray activatable caged compounds, azo compounds are designed and synthesized with a positive charge and long π‐conjugated system to increase the reaction efficiency with hydrated electrons. The azo bonds in the designed compounds are selectively cleaved by X‐ray, and the fluorescent substance Diethyl Rhodamine is released. Based on the results of experiments and quantum chemical calculations, azo bond cleavage is assumed to occur via a two‐step process: a two‐electron reduction of the azo bond followed by N─N bond cleavage. Cellular experiments also demonstrate that the azo bonds can be cleaved intracellularly. Thus, caged compounds that can be activated by an azo bond cleavage reaction promoted by X‐ray are successfully generated.

Abstract The linkage between environmental conditions in the coastal ocean and the open sea varies greatly by region. It is important to clarify, on an area-by-area basis, what coastal monitoring information reveals about the open ocean and how much predictive information for the open ocean may be applicable to the coastal ocean. The Pacific Ocean off the coast of Peru is a monitoring area for the El Niño/La Niña, an oceanic–atmospheric phenomenon of global importance. However, there are not many reliable data along the Peruvian coast. We deployed a network of 6 logger sites along the Peruvian coast during 2017–2020 and compiled a useful, high-resolution dataset of water temperatures. We examined a possible link between temperatures in the coastal waters of Peru and the open sea by comparing the new dataset with historical temperatures in the open ocean. We confirmed that monthly mean anomalies of seashore water temperatures in coastal Peru were strongly correlated with those of open ocean sea surface temperatures. With one exception, the correlation coefficients ranged from 0.80 to 0.92 and were significant at p

Pseudomonas aeruginosa infection is an infectious disease that must be controlled because it becomes chronic and difficult to treat, owing to its unique system of toxin production/injection and elimination of other bacteria. Here, we noninvasively monitored P. aeruginosa using single-photon emission computed tomography (SPECT) imaging. Determining the amount and localization of the P. aeruginosa will enable making faster clinical diagnoses and selecting the most appropriate therapeutic agents and methods. Nonclinically, this information can be used for imaging in combination with biofilms and toxin probes and will be useful for discovering drugs targeting P. aeruginosa. To study P. aeruginosa accumulation, we conducted in vitro and in vivo studies using iodine-123 β-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP), which we previously reported using for Escherichia coli. In vitro, 123I-BMIPP accumulated in P. aeruginosa by being taken up into the bacteria and adsorbing to the bacterial surface. In vivo, 123I-BMIPP accumulated significantly more in infected sites than in noninfected sites and could be quantified by SPECT. These results suggest that 123I-BMIPP can be used as a probe for P. aeruginosa for SPECT. Establishing a noninvasive monitoring method using SPECT will allow further progress in studying P. aeruginosa.

Background: Management of docetaxel-induced edema is important as severe edema may lead to discontinuation of chemotherapy. Patients with stage IV breast cancer (BC) treated with docetaxel have shown lower limb edema; however, details of its developmental and healing processes are unknown, and thus management strategies have not been established. The aim of this study was to investigate the characteristics of the development and healing process of docetaxel-induced lower limb edema in stage IV BC patients. Methods: This prospective observational study was conducted on patients with BC who were administered docetaxel between September 2020 and September 2021 at a National Hospital in Japan. Skin changes such as pitting test, circumference, along with ultrasound images and subjective symptom changes were evaluated. The progression of these changes was compared between patients with stage IV and non-stage IV disease. Results: Five patients were enrolled in the study, of which two and one patients with stage IV and non-stage IV disease, respectively, developed lower limb edema. Early signs of lower limb edema were observed in ultrasound images, 15?cm below the peroneal head, before edema was confirmed by the pitting test and subjective symptoms. In patients with stage IV disease, edema worsened to Grade 3, and reduced four months after the end of drug administration. Conclusion: For patients with stage IV disease, care should be initiated from the time the early signs are observed using ultrasound and continued for up to four months after the end of docetaxel administration.

In recent years, autonomous mobile robots have significantly increased in prevalence due to their ability to augment and diversify the workforce. One critical aspect of their operation is effective local path planning, which considers dynamic constraints. In this context, the Dynamic Window Approach (DWA) has been widely recognized as a robust local path planning. DWA produces a set of path candidates derived from velocity space subject to dynamic constraints. An optimal path is selected from path candidates through an evaluation function guided by fixed weight coefficients. However, fixed weight coefficients are typically designed for a specific environmental context. Consequently, changes in environmental conditions such as congestion levels, road width, and obstacle density could potentially lead the evaluation function to select inefficient paths or even result in collisions. To overcome this challenge, this paper proposes the dynamic weight coefficients based on Q-learning for DWA (DQDWA). The proposed method uses a pre-learned Q-table that comprises robot states, environmental conditions, and actions of weight coefficients. DQDWA can use the pre-learned Q-table to dynamically select optimal paths and weight coefficients that better adapt to varying environmental conditions. The performance of DQDWA was validated through extensive simulations and real experiments to confirm its ability to enhance the effectiveness of local path planning.

This paper proposes a path planning method for a nonholonomic mobile robot that takes turnabouts on a narrow road. A narrow road is any space in which the robot cannot move without turning around. Conventional path planning techniques ignore turnabout points and directions determined by environmental data, which might result in collisions or deadlocks on a narrow road. The proposed method uses the Deep Q-network (DQN) to obtain a control strategy for path planning on narrow roads. In the simulation, the robot learned the optimal velocity commands that maximized the long-term reward. The reward is designed to reach a target with a smaller change in robot velocity and fewer turnabouts. The success rate and the number of turnabouts in the simulation and experiment were used to evaluate the trained model. According to simulation and environmental data, the proposed strategy enables the robot to travel on narrow roads. Additionally, these outcomes demonstrate comparable performance on a number of roadways that are not part of the learning environments, supporting the robustness of the trained model.

The aim of the current study was to determine the effects of cerebral contusion injury with purinergic adenosine triphosphate Y1 (P2Y1) receptor blockers on postinjury inflammatory responses. Adenosine triphosphate (ATP) is released into the extracellular space in several in vivo models, including traumatic brain injury. Released ATP triggers neuroinflammation via activation of microglial cells. P2Y1 receptor blockers were reported to suppress extracellular ATP elevation in several disease models through inhibition of cellular ATP release. In addition to the beneficial effects of inflammation, excess inflammatory reactions cause secondary damage and aggravate outcomes. Here, we assessed the effect of the selective P2Y1 receptor blocker MRS2179 on its potential to prevent posttraumatic inflammation in a rat cerebral contusion model. Cerebral contusion injury was induced in the rat cerebral cortex. Either MRS2179 or artificial cerebral spinal fluid as a control was administered in situ into the center of contused tissue via a subcutaneously implanted osmotic pump. Galectin 3, a marker of microglia and proinflammatory cytokines, was measured 1, 3 and 7 days following injury. Another group of rats was assessed for behavioral performance up to 28 days after injury, including the beam walk test, neurological response test and plus maze test. The Galectin 3 levels in the cortex around the contusion cavity and in the cortex far from the contusion cavity were significantly suppressed by MRS2179 administration on postinjury Days 1 and 3 (p

Abstract Background Coronavirus disease 2019 (COVID‐19) is known to cause not only respiratory but also neuropsychiatric symptoms, which are assumed to be derived from a cytokine storm and its effects on the central nervous systems. Patients with COVID‐19 who develop severe respiratory symptoms are known to show severe neuropsychiatric symptoms such as cerebrovascular disease and encephalopathy. However, the detailed clinical courses of patients with neuropsychiatric symptoms caused by mild or asymptomatic COVID‐19 remain poorly understood. Here, we present a case of COVID‐19 who presented with severe and prolonged neuropsychiatric symptoms subsequent to mild respiratory symptoms. Case presentation A 55‐year‐old female with COVID‐19 accompanied by mild respiratory symptoms showed delusion, psychomotor excitement, and poor communication ability during quarantine outside the hospital. Considering her diminished respiratory symptoms, her neuropsychiatric symptoms were initially regarded as psychogenic reactions. However, as she showed progressive disturbance of consciousness accompanied by an abnormal electroencephalogram, she was diagnosed with post‐COVID‐19 encephalopathy. Although her impaired consciousness and elevated cytokine level improved after steroid pulse therapy, several neuropsychiatric symptoms, including a loss of concentration, unsteadiness while walking, and fatigue, remained. Conclusions This case suggests the importance of both recognizing that even apparently mild COVID‐19‐related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms, and elucidating the mechanisms, treatment, and long‐term course of COVID‐19‐related neuropsychiatric symptoms in the future.

Local path planning considering static and dynamic obstacles for a mobile robot is one of challenging research topics. Conventional local path planning methods generate path candidates by assuming constant velocities for a certain period time. Therefore, path candidates consist of straight line and arc paths. These path candidates are not suitable for dynamic environments and narrow spaces. This paper proposes a novel local path planning method based on dynamic window approach with virtual manipulators (DWV). DWV consists of dynamic window approach (DWA) and virtual manipulator (VM). DWA is the local path planning method that performs obstacle avoidance for static obstacles under robot constraints. DWA also generates straight line and arc path candidates by assuming constant velocities. VM generates velocities of reflective motion by using virtual manipulators and environmental information. DWV generates path candidates by variable velocities modified by VM and predicted positions of static and dynamic obstacles. Therefore, in an environment with dynamic obstacles, the obstacle-avoidable paths which include non-straight line and non-arc paths are generated. The effectiveness of the proposed method was confirmed from simulation and experimental results.

Chemoradiotherapy is frequently used to treat cancer. Stereotactic body radiotherapy (SBRT) is a single high-dose radiotherapy used to treat a variety of cancers. The anticancer drug methotrexate (MTX) shows affinity for solute carrier (SLC) and ATP-binding cassette (ABC) transporters. This study investigated relationships between accumulation of methotrexate and gene expression levels of solute carrier and ATP-binding cassette transporters in cancer cells after a single and high-dose X-ray irradiation. Cancer cell lines were selected from lung and cervical cancer cell line that are commonly used for stereotactic body radiotherapy and effective with methotrexate. We examined expression levels of organic anion-transporting polypeptide (OATP)1B1, OATP1B3, OATP1B7, and organic anion transporter (OAT)1 as solute carrier transporters and multidrug resistance-associated protein (MRP)1 and MRP2 as ATP-binding cassette transporters, using real-time polymerase chain reaction and accumulation of 3H-MTX in cancer cells after 10-Gy irradiation, assuming stereotactic body radiotherapy. Cells were divided into three groups: Control without irradiation; 4 h after irradiation; and 24 h after irradiation. In control, gene expression levels of OAT1 in all cells was below the limit of measurement. After irradiation, gene expression levels of OATP1B1/1B3/1B7 showed changes in each cell line. Gene expression levels of MRP1/2 tended to increase after irradiation. Gene expression levels of OATP1B1/1B3/1B7 were much lower than those of MRP1/2. Accumulation of 3H-MTX tended to decrease over time after irradiation. Irradiation of cancer cells thus alters gene expression levels of both solute carrier transporters (OATP1B1/1B3/1B7) and ABC transporters (MRP1/2) and decreases accumulation of 3H-MTX in cancer cells over time due to elevated expression of MRP1/2.

Introduction: Gout is a chronic metabolic disorder secondary to hyperuricemia and is typically characterized initially by monoarticular arthritis starting at the distal extremities and may progress to tophaceous gout after several years of acute attacks of painful inflammatory arthropathy. Case presentation: We present a case of erosive polyarticular tophaceous gout with an atypical presentation of painless masses of both hands and severe osteolysis without periarticular osteopenia on radiographs. Laboratory examinations were requested, and the diagnosis was confirmed with a biopsy. She was started with pharmacologic therapy but due to the severity of the joint destruction and deformities, surgical debridement and arthrodesis was done for the distal interphalangeal joints of the right middle and ring finger, along with the metacarpophalangeal joint of the right thumb. Non-union and implant failure of the metacarpophalangeal arthrodesis occurred but there was noted improvement of her hand function. Conclusion: This case should be differentiated from multicentric reticular histiocytosis, rheumatoid arthritis, and psoriatic arthritis. Surgical treatment, such as joint fusion, may be effective in some cases of gouty nodules.

Abstract The differentiation of non-small cell lung cancer (NSCLC) and radiation pneumonitis (RP) is critically essential for selecting optimal clinical therapeutic strategies to manage post carbon-ion radiotherapy (CIRT) in patients with NSCLC. The aim of this study was to assess the ability of 18F-FDG PET/CT metabolic parameters and its textural image features to differentiate NSCLC from RP after CIRT to develop a differential diagnosis of malignancy and benign lesion. We retrospectively analyzed 18F-FDG PET/CT image data from 32 patients with histopathologically proven NSCLC who were scheduled to undergo CIRT and 31 patients diagnosed with RP after CIRT. The SUV parameters, metabolic tumor volume (MTV), total lesion glycolysis (TLG) as well as fifty-six texture parameters derived from seven matrices were determined using PETSTAT image-analysis software. Data were statistically compared between NSCLC and RP using Wilcoxon rank-sum tests. Diagnostic accuracy was assessed using receiver operating characteristics (ROC) curves. Several texture parameters significantly differed between NSCLC and RP (p

Abstract Background Patient participation is a key foundation of advance care planning (ACP). However, a patient himself/herself may be left out from sensitive conversations such as end-of-life (EOL) care discussions. The objectives of this study were to investigate patients’ participation rate in the discussion of Cardiopulmonary Resuscitation (CPR) / Do-Not-Attempt-Resuscitation (DNAR) order, and in the discussion that the patient is at his/her EOL stage (EOL disclosure), and to explore their associated factors. Methods This is a retrospective chart review study. The participants were all the patients who were hospitalized and died in a university-affiliated teaching hospital (tertiary medical facility) in central Tokyo, Japan during the period from April 2018 to March 2019. The following patients were excluded: (1) cardiopulmonary arrest on arrival; (2) stillbirth; (3) under 18 years old at the time of death; and (4) refusal by their bereaved family. Presence or absence of CPR/DNAR discussion and EOL disclosure, patients’ involvement in those discussions, and their associated factors were investigated. Results CPR/DNAR discussions were observed in 336 out of the 358 patients (93.9%). However, 224 of these discussions were carried out without a patient (patient participation rate 33.3%). Male gender (odds ratio (OR) = 2.37 [95% confidence interval (CI) 1.32–4.25]), living alone (OR = 2.51 [1.34–4.71]), and 1 year or more from the date of diagnosis (OR = 1.78 [1.03–3.10]) were associated with higher patient’s participation in CPR/DNAR discussions. The EOL disclosure was observed in 341 out of the 358 patients (95.3%). However, 170 of the discussions were carried out without the patient (patient participation rate 50.1%). Patients who died of cancer (OR = 2.41[1.45–4.03]) and patients without mental illness (OR=2.41 [1.11–5.25]) were more likely to participate in EOL disclosure. Conclusions In this clinical sample, only up to half of the patients participated in CPR/DNAR discussions and EOL disclosure. Female, living with family, a shorter period from the diagnosis, non-cancer, and mental illness presence are risk factors for lack of patients’ participation in CPR/DNAR or EOL discussions. Further attempts to facilitate patients’ participation, based on their preference, are warranted.

Abstract Background Meningiomas are the most common benign intracranial tumors, and commonly comprise high-vascularizing but slow-growing tumors. On the other hand, meningiomas arising from the ventricular system are of rare occurrence, and spontaneous hemorrhage is an infrequent event. Case presentation We describe here the rare clinical manifestations of a 28-year-old female with acute intracranial hemorrhage located in the trigone of the lateral ventricle who was initially thought to have suffered an acute cerebrovascular accident, but was subsequently confirmed to have a benign intraventricular meningioma. To clarify the clinical features of such a rare course of meningioma, we also present a short literature review of acute intracranial hemorrhage caused by intraventricular meningioma. Conclusions Ventricular meningioma presenting with hemorrhage such as acute stroke is a rare event, but recognition of such a pathogenesis is important. Although further accumulation of clinical data is needed, we suggest that early surgery should be undertaken in patients with lateral ventricular meningioma, even if it is not so large or asymptomatic.

Abstract Purpose Chondrocyte -based tissue engineering has been a promising option for the treatment of cartilage lesions. In previous literature, TD198946 has been shown to promote chondrogenic differentiation which could prove useful in cartilage regeneration therapies. Our study aimed to investigate the effects of TD198946 in generating engineered cartilage using dedifferentiated chondrocyte-seeded collagen scaffolds treated with TD198946. Methods Articular chondrocytes were isolated from mini pig knees and expanded in 2-dimensional cell culture and subsequently used in the experiments. 3-D pellets were then cultured for two weeks. Cells were also cultured in a type I collagen scaffolds for four weeks. Specimens were cultured with TD198946, BMP-2, or both in combination. Outcomes were determined by gene expression levels of RUNX1, SOX9, ACAN, COL1A1, COL2A1 and COL10A1, the glycosaminoglycan content, and characteristics of histology and immunohistochemistry. Furthermore, the maturity of the engineered cartilage cultured for two weeks was evaluated through subcutaneous implantation in nude mice for four weeks. Results Addition of TD198946 demonstrated the upregulation of gene expression level except for ACAN, type II collagen and glycosaminoglycan synthesis in both pellet and 3D scaffold cultures. TD198946 and BMP-2 combination cultures showed higher chondrogenic differentiation than TD198946 or BMP-2 alone. The engineered cartilage maintained its extracellular matrices for four weeks post implantation. In contrast, engineered cartilage treated with either TD198946 or BMP-2 alone was mostly absorbed. Conclusions Our results indicate that TD198946 could improve quality of engineered cartilage by redifferentiation of dedifferentiated chondrocytes pre-implantation and promoting collagen and glycosaminoglycan synthesis.

We evaluated the whole-body distribution of orally-administered radioiodine-125 labeled acetaminophen (125I-AP) to estimate gastrointestinal absorption of anionic drugs. 125I-AP was added to human embryonic kidney (HEK)293 and Flp293 cells expressing human organic anion transporting polypeptide (OATP)1B1/3, OATP2B1, organic anion transporter (OAT)1/2/3, or carnitine/organic cation transporter (OCTN)2, with and without bromosulfalein (OATP and multidrug resistance-associated protein (MRP) inhibitor) and probenecid (OAT and MRP inhibitor). The biological distribution in mice was determined by oral administration of 125I-AP with and without bromosulfalein and by intravenous administration of 125I-AP. The uptake of 125I-AP was significantly higher in HEK293/OATP1B1, OATP1B3, OATP2B1, OAT1, and OAT2 cells than that in mock cells. Bromosulfalein and probenecid inhibited OATP- and OAT-mediated uptake, respectively. Moreover, 125I-AP was easily excreted in the urine when administered intravenously. The accumulation of 125I-AP was significantly lower in the blood and urinary bladder of mice receiving oral administration of both 125I-AP and bromosulfalein than those receiving only 125I-AP, but significantly higher in the small intestine due to inhibition of OATPs and/or MRPs. This study indicates that whole-body distribution after oral 125I-AP administration can be used to estimate gastrointestinal absorption in the small intestine via OATPs, OATs, and/or MRPs by measuring radioactivity in the urinary bladder.

Central dural tenting sutures are surgical routine procedure in craniotomy which requires passing the thread through a small bone hole, which is time consuming and both physically and mentally stressful. We have developed a novel surgical device to easily perform these procedures and to reduce stress. This study evaluated the convenience, ease, and accuracy compared to conventional methods. We evaluated the time taken using the bone hole threader with an artificial bone model with 10 bone holes. The time required to pass the sutures through the bone hole was compared after 11 neurosurgeons performed using each of three methods twice: one surgeon and another assistant using the conventional method, one surgeon using the bone hole threader, and one surgeon and another assistant using the bone hole threader. These results were statistically analyzed using SPSS. Mean time reduction of 15.9 s was obtained for the bone threader use by one surgeon compared with conventional method by two operators (p = 0.03). Mean time reduction of 24 s was obtained for the bone threader use by two operators compared with one operator (p

In order to improve the treatment outcome of endoscopic transsphenoidal surgery (eTSS), it is important to identify the factors that contribute to the tumor resection rate and/or post-operative complications, and to devise a surgical strategy for each case. In the present study, we retrospectively evaluated our own experience of eTSS for primary pituitary adenoma (PA), and sought the factors that are related to patients’ surgical outcomes. Thirty-three cases of primary PA operated on by eTSS at our institution in a recent 5-year period were investigated. The patients’ data for age, sex, Knosp grade, operating time, sellar floor opening rate, tumor resection rate and post-operative complications were evaluated. The median rate of tumor resection was 91.3%, and the tumor resection rate demonstrated significant linear relationships with age (Z = −0.41, p = 0.02), sex (Z = −0.42, p = 0.01) and sellar floor opening rate (Z = 0.47, p = 0.01). A significant linear relationship was also found between sex and sellar floor opening rate (Z = −0.51, p

In this study, we evaluated the use of 15-(4-123I-iodophenyl)-3(R,S)-methylpentadecanoic acid (123I-BMIPP) to visualize fatty acid metabolism in bacteria for bacterial infection imaging. We found that 123I-BMIPP, which is used for fatty acid metabolism scintigraphy in Japan, accumulated markedly in Escherichia coli EC-14 similar to 18F-FDG, which has previously been studied for bacterial imaging. To elucidate the underlying mechanism, we evaluated changes in 123I-BMIPP accumulation under low-temperature conditions and in the presence of a CD36 inhibitor. The uptake of 123I-BMIPP by EC-14 was mediated via the CD36-like fatty-acid-transporting membrane protein and accumulated by fatty acid metabolism. In model mice infected with EC-14, the biological distribution and whole-body imaging were assessed using 123I-BMIPP and 18F-FDG. The 123I-BMIPP biodistribution study showed that, 8 h after infection, the ratio of 123I-BMIPP accumulated in infected muscle to that in control muscle was 1.31 at 60 min after 123I-BMIPP injection. In whole-body imaging 1.5 h after 123I-BMIPP administration and 9.5 h after infection, infected muscle exhibited a 1.33-times higher contrast than non-infected muscle. Thus, 123I-BMIPP shows potential for visualizing fatty acid metabolism of bacteria for imaging bacterial infections.

Single-photon emission computed tomography (SPECT) imaging using intravenous radioactive ligand administration to indirectly evaluate the time-dependent effect of intranasal drugs with poor blood-brain barrier permeability on brain drug distributions in mice was evaluated. The biodistribution was examined using domperidone, a dopamine D2 receptor ligand, as the model drug, with intranasal administration at 0, 15, or 30 min before intravenous [123I]IBZM administration. In the striatum, [123I]IBZM accumulation was significantly lower after intranasal (IN) domperidone administration than in controls 15 min after intravenous [125I]IBZM administration. [123I]IBZM SPECT was acquired with intravenous (IV) or IN domperidone administration 15 min before [123I]IBZM, and time–activity curves were obtained. In the striatum, [123I]IBZM accumulation was clearly lower in the IN group than in the control and IV groups. Time–activity curves showed no significant difference between the control and IV groups in the striatum, and values were significantly lowest during the first 10 min in the IN group. In the IN group, binding potential and % of receptor occupancy were significantly lower and higher, respectively, compared to the control and IV groups. Thus, brain-migrated domperidone inhibited D2R binding of [123I]IBZM. SPECT imaging is suitable for research to indirectly explore nose-to-brain drug delivery and locus-specific biological distribution.

Various remote-controlled methods have been developed to improve operability using force or visual assists; however, using only force or visual assists may deteriorate the operability or safety performance. Therefore, a remote-controlled method with both force and visual assists is proposed to improve the operability while maintaining safety performance. The proposed remote-controlled system consists of a wheeled mobile robot, control device, and monitor. The force assist is generated using the time to collision (TTC), which is the predicted time of collision of the mobile robot against an obstacle. This force assist is applied to the operator using a control device to achieve collision avoidance. Using a visual assist, a predicted trajectory for the mobile robot based on the TTC is generated. For operability improvement, this predicted trajectory with color gradation is shown on the monitor. In summary, the achievement of operability improvement while maintaining safety performance is confirmed from experimental results using the proposed method.

Abstract Background Ketamine is a potent sedative drug that helps to maintain upper‐airway patency, due to its higher upper‐airway dilator muscular activity and higher level of duty cycle, as seen in rats. However, no clinical trials have tested passive upper‐airway collapsibility and changes in the inspiratory duty cycle against partial upper‐airway obstruction in humans. The present study evaluated both the passive mechanical upper‐airway collapsibility and compensatory response against acute partial upper‐airway obstruction using three different sedative drugs in a crossover trial. Methods Eight male volunteers entered this nonblinded, randomized crossover study. Upper‐airway collapsibility (passive critical closing pressure) and inspiratory duty cycle were measured under moderate sedation with ketamine, propofol, and dexmedetomidine. Propofol, dexmedetomidine, and ketamine anesthesia were induced to obtain adequate, same‐level sedation, with a BIS value of 50–70 and the OAA/S score of 2–3 and RASS score of −3. Results The median passive critical closing pressure of 0.08 [−5.51 to 1.20] cm H2O was not significantly different compared to that of propofol sedation (−0.32 [−1.41 to −0.19] cm H2O) and of dexmedetomidine sedation (−0.28 [−0.95 to −0.03] cm H2O) (p = .045). The median passive RUS for ketamine 54.35 [32.00 to 117.50] cm H2O/L/s was significantly higher than that for propofol 5.50 [2.475 to 19.60] cm H2O/L/s; (mean difference, 27.50; 95% CI 9.17 to 45.83) (p = .009) and for dexmedetomidine 19.25 [4.125 to 22.05] cm H2O/L/s; (mean difference, 22.88; 95% CI 4.67 to 41.09) (p = .021). The inspiratory duty cycle increased significantly as the inspiratory airflow decreased in passive conditions for each sedative drug, but behavior differed among the three sedative drugs. Conclusion Our findings demonstrate that ketamine sedation may have an advantage of both maintained passive upper‐airway collapsibility and a compensatory respiratory response, due to both increase in neuromuscular activity and the increased duty cycle, to acute partial upper‐airway obstruction.

Abstract Background Erythropoietin-producing uterine myoma can cause various complications such as arterial or venous thrombosis and bleeding. Therefore, caution is required in the anesthetic management of affected patients. Case presentation A 57-year-old female was suspected to have an erythropoietin-producing uterine myoma and was scheduled to undergo an abdominal total hysterectomy and bilateral salpingo-oophorectomy. Preoperative levels of hemoglobin and erythropoietin were 21.9 g/dl (normal 11.5–15 g/dl) and 23.2 IU/ml (normal 4.2–23.7 IU/ml), respectively. Preoperative phlebotomy and isovolemic hemodilution were performed to prevent arterial and venous thrombosis, following previous evidence that a hemoglobin level

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [123I]MIBG administration. [123I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [123I]MIBG with and without cimetidine. [123I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [123I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [123I]MIBG injection. [123I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.

The accumulation of high levels of 99mTc-tetrofosmin (99mTc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of 99mTc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce 99mTc-TF hepatic accumulation. In this in vitro study, 99mTc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na+-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to 99mTc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to 99mTc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the 99mTc-TF uptake ratio was calculated from SPECT. From the in vitro study, 99mTc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the 99mTc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of 99mTc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of 99mTc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce 99mTc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality.

Abstract Translocator protein (TSPO) is a biomarker for detecting neuroinflammation by PET. 11C-(R)-PK11195 has been used to image TSPO since the 1980s. Here, we compared the utility of four 11C-labeled ligands—(R)-PK11195, PBR28, DPA-713, and ER176—to quantify TSPO in healthy humans. For all of these ligands, BP ND (specific-to-non-displaceable ratio of distribution volumes) was measured by partially blocking specific binding with XNBD173 administration. In high-affinity binders, DPA-713 showed the highest BP ND of 7.3 followed by ER176 (4.2), PBR28 (1.2), and PK11195 (0.8). Only ER176 allows the inclusion of low-affinity binders because of little influence of radiometabolites and high BP ND. If inclusion of all three genotypes is important for study logistics, ER176 is the best of these four radioligands for studying neuroinflammation.

The Mekong Delta, situated between Cambodia and Vietnam, is one of the most productive aquifer systems in the region. In recent years, however, several studies have shown that groundwater in several areas of the delta is highly contaminated with arsenic (As). Although more than 80% of the total area of the Mekong Delta is situated in Vietnam, most of the studies have been conducted on the Cambodian-side of the delta. In this study, borehole core samples were collected around the Tien and Hau Rivers, the two main branches of the Mekong River as it enters Vietnam. We present a raw data collection of the chemical and mineralogical composition of distinct lithological features from six borehole core samples drilled up to a depth of 40 m. The data also include the pH, Eh, EC, As, Si, Al, DOC, dissolved heavy metals (Fe and Mn) and major coexisting ions of leachates obtained by leaching the 34 selected sediment samples in deionized water. The information provided in this paper would be useful as a baseline for reactive transport or geochemical modeling to understand and predict As migration in naturally contaminated aquifers under various conditions. For more insights, the reader is referred to our paper entitled “The solid-phase partitioning of arsenic in unconsolidated sediments of the Mekong Delta, Vietnam and its modes of release under various conditions” Huyen et al., 2019.

BackgroundAlthough a 3-arm DOTA construct, which has three carboxylic acids, h has been applied for conjugation to many peptides, we investigated if a 4-arm DOTA construct conjugated to peptides improves chemical properties for melanoma imaging of the melanocortin 1 receptor compared to 3-arm DOTA-conjugated peptides.MethodsSpecific activities, radiolabeling efficiencies, and partition coefficients were evaluated using 111In-labeled 3-arm and 4-arm DOTA-α-melanocyte-stimulating hormone (MSH). For assessment of MC1-R affinity and accumulation in tumor cells in vitro, B16-F1 melanoma and/or 4T1 breast cancer cells were incubated with 111In-labeled 3-arm and 4-arm DOTA-α-MSH with and without α-MSH as a substrate. The stability was evaluated using mouse liver homogenates and plasma. Biological distribution and whole-body single photon emission computed tomography imaging of 111In-labeled 3-arm and 4-arm DOTA-α-MSH were obtained using B16-F1 melanoma-bearing mice.ResultsSpecific activities and radiolabeling efficiencies of both radiotracers were about 1.2 MBq/nM and 90-95%, respectively. The partition coefficients were -0.28 ± 0.03 for 111In-labeled 3-arm DOTA-α-MSH and -0.13 ± 0.04 for 111In-labeled 4-arm DOTA-α-MSH. Although accumulation was significantly inhibited by α-MSH in B16-F1 cells, the inhibition rate of 111In-labeled 4-arm DOTA-α-MSH was lower than that of 111In-labeled 3-arm DOTA-α-MSH. 111In-labeled 4-arm DOTA-α-MSH was taken up early into B16-F1 cells and showed higher accumulation than 111In-labeled 3-arm DOTA-α-MSH after 10 min of incubation. Although these stabilities were relatively high, the stability of 111In-labeled 4-arm DOTA-α-MSH was higher than that of 111In-labeled 3-arm DOTA-α-MSH. Regarding biological distribution, 111In-labeled 4-arm DOTA-α-MSH showed significantly lower average renal accumulation (1.38-fold) and significantly higher average melanoma accumulation (1.32-fold) than 111In-labeled 3-arm DOTA-α-MSH at all acquisition times. 111In-labeled 4-arm DOTA-α-MSH showed significantly higher melanoma-to-kidney, melanoma-to-blood, and melanoma-to-muscle ratios than 111In-labeled 3-arm DOTA-α-MSH.ConclusionsThe 4-arm DOTA construct has better chemical properties for peptide radiotracers than the 3-arm DOTA construct.

Ultrasonography (US) is useful for visual detection of edematous tissues to assess subcutaneous echogenicity. However, visualization of subcutaneous echogenicity is interpreted differently among operators because the evaluation is subjective and individual operators have unique knowledge. This study objectively assessed leg edema using US with a gel pad including fat for normalization of echogenicity in subcutaneous tissue. Five younger adults and four elderly people with leg edema were recruited. We compared assessments of US and limb circumference before and after the intervention of vibration to decrease edema in younger adults, and edema prior to going to sleep and reduced edema in the early morning in elderly people. These assessments were performed twice in elderly people by three operators and reliability, interrater differences, and bias were assessed. For US assessment, echogenicity in subcutaneous tissue was normalized to that of the gel pad by dividing the mean echogenicity of subcutaneous tissue by the mean echogenicity of the gel pad. In younger adults, the normalized subcutaneous echogenicity before the intervention was significantly higher than that after the intervention. In elderly people, echogenicity indicating edema was significantly higher than that after edema reduction. Edema was detected with accuracy rates of 76.9% in younger adults and 75.0% in elderly people. Meanwhile, limb circumference could be used to detect edema in 50.0% of healthy adults and 87.8% of elderly people. The intra-reliability was excellent (intraclass correlation coefficient > 0.9, p < 0.01), and the inter-reliability was good (intraclass correlation coefficient > 0.7, p < 0.01) for normalized subcutaneous echogenicity. Bland-Altman plots revealed that inter-rater differences and systematic bias were small. Normalized subcutaneous echogenicity with the pad can sensitively and objectively assess leg edema with high reliability. Therefore, this method has the potential to become a new gold standard for objective assessment of leg edema in clinical practice.

Continuous maintenance of an appropriate position of the mandible and head purely by manual manipulation is difficult, although the maneuver can restore airway patency during sleep and anesthesia. The aim of this paper was to examine the effect of head elevation with jaw closure using a remote-controlled airbag device, such as the airbag system, on passive upper airway collapsibility during propofol anesthesia. Seven male subjects were studied. Propofol infusion was used for anesthesia induction and maintenance, with a target blood propofol concentration of 1.5-2 μg/ml. Nasal mask pressure (PN) was intermittently reduced to evaluate upper airway collapsibility (passive PCRIT) and upstream resistance (RUS) at three different head and jaw positions, jaw opening position in the supine position, jaw opening position in the sniffing position with 6-cm head elevation, and jaw closure at a 6-cm height sniffing position. The 6-cm height sniffing position with jaw closure was achieved by an airbag device that was attached to the subject's head-like headgear. Patient demographics, PCRIT and RUS in each condition were compared using one-way ANOVA with a post hoc Tukey test. P CRIT ~ -3.4-cm H2O) compared with the baseline position (PCRIT ~ -0.8-cm H2O, P = 0.0001). In the clinical study, there was improvement of upper airway obstruction in sleep apnea patients, including decreased apnea and hypopnea duration and increased the lowest level of oxygen saturation. We demonstrated that establishment of head elevation with jaw closure achieved by a remote-controlled airbag device using an inflatable airbag system can produce substantial decreases in upper airway collapsibility and maintain upper airway patency during propofol anesthesia and sleep.

OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood of DLE patients and evaluate their ability to suppress autologous T cells. METHODS/STUDY POPULATION: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 32 CLE patients and 16 age-matched and gender-matched controls were analyzed using flow cytometry. Monocytic MDSCs were identified by the phenotype of CD14+ HLA-DR neg/low. Furthermore, autologous MDSCs and T cells were purified from CLE PBMCs (n=4) and co-cultured at different ratios of these cells. T cell function was measured by secretion of IFN-γ by ELISA. RESULTS/ANTICIPATED RESULTS: Monocytic MDSCs in CLE PBMCs (median: 2.04%, IQR: 0.67%–5.07%) were significantly higher compared with healthy control PBMCs (median: 0.5%, IQR: 0.1%–1.07%, p=0.002). Although not significant on subset analysis, patients with CLE limited to the head and neck had the highest levels of MDSCs. CLE MDSCs (n=4) were found to suppress autologous activated T-cells in a dose-dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: In this cross-sectional study of patients of the UT Southwestern Cutaneous Lupus Registry, we observed differences in the levels of MDSCs among PBMCs of CLE patients Versus healthy controls. CLE patients had significantly higher levels of MDSCs, which could be explained by the presence of an inflammatory state in this group. Furthermore, CLE MDSCs were able to suppress autologous T cells, showing that these cells are functionally patent in CLE blood. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity.

Animals are assumed to obtain/conserve energy effectively to maximise their fitness, which manifests itself in a variety of behavioral strategies. For marine animals, however, these behavioral strategies are generally unknown due to the lack of high-resolution monitoring techniques in marine habitats. As large marine herbivores, immature green turtles do not need to allocate energy to reproduction but are at risk of shark predation, although it is a rare occurrence. They are therefore assumed to select/use feeding and resting sites that maximise their fitness in terms of somatic growth, while avoiding predation. We investigated fine-scale behavioral patterns (feeding, resting and other behaviors), microhabitat use and time spent on each behavior for eight immature green turtles using data loggers including: depth, global positioning system, head acceleration, speed and video sensors. Immature green turtles at Iriomote Island, Japan, spent an average of 4.8 h feeding on seagrass each day, with two peaks, between 5∶00 and 9∶00, and between 17∶00 and 20∶00. This feeding pattern appeared to be restricted by gut capacity, and thus maximised energy acquisition. Meanwhile, most of the remaining time was spent resting at locations close to feeding grounds, which allowed turtles to conserve energy spent travelling and reduced the duration of periods exposed to predation. These behavioral patterns and time allocations allow immature green turtles to effectively obtain/conserve energy for growth, thus maximising their fitness.