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Intraneural ganglia are rare, benign cysts that form within the epineurium of the affected nerve. Patients present with features of compressive neuropathy, including numbness. We report a 74-year-old male patient with pain and numbness on his right thumb of 1-year duration. Magnetic resonance imaging revealed a cystic lesion with a possible scaphotrapezium-trapezoid joint connection. The articular branch was not identified during the surgery and decompression with excision of the cyst wall was done. A recurrence of the mass was noted 3 years later, but the patient was asymptomatic and no additional intervention was done. Decompression alone can relieve the symptoms of an intraneural ganglion, but excision of the articular branch may be essential in preventing its recurrence. Level of Evidence: Level V (Therapeutic)

We present a patient with Pacinian corpuscle hypertrophy and hyperplasia in the hand and discuss the diagnosis and treatment of this rare condition. A 46-year-old woman presented with radiating pain of the left middle finger. A strong Tinel-like sign was elicited between the index and middle fingers. The patient frequently used mobile phone, with the corner of the phone consistently applying pressure on the palm. The surgery was carried out under the microscope and two enlarged cystic lesions under the epineurium were found in the proper digital nerve. Histologic examination revealed hypertrophied Pacinian corpuscle with normal structure. Postoperatively, her symptoms gradually improved. Preoperative diagnosis of this disease is very difficult. Hand surgeons should keep this disease in mind preoperatively. In our case, we would not have been able to identify multiple hypertrophic Pacinian corpuscles without the microscope. An operating microscope is recommended in a surgery of this nature. Level of Evidence: Level V (Therapeutic)

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.

By repeatedly utilizing the MC-AFIR method, a comprehensive reaction-path search for the oligomerization of HMF was conducted to clarify the mechanism of humin formation in the oxidation of HMF to FDCA.

In this study, cauda epididymal sperm were collected from Amur leopard cats with various causes of death as well as Tsushima leopard cats that underwent castration surgery, and sperm quality was compared with that in domestic cats. A sufficient number of sperm similar to those in domestic cats could be collected from the cauda epididymis of Amur leopard cats. However, in old leopard cats, no or very few cauda epididymal sperm were recovered, although there were no differences in sperm motility and sperm abnormality. There were no significant differences in sperm quality immediately after collection and after freezing-thawing of cauda epididymal sperm compared with corresponding estimates in domestic cats.

Background Patients with neurofibromatosis type 1 (NF1) have various vascular diseases due to the vascular fragility, but no reports of case of giant thrombotic aneurysm was found. We treated a rare case of giant thrombotic aneurysm of the internal carotid artery (ICA) in a patient with NF1. Case Presentation A 60-year-old man had suffered deteriorating visual loss and homonymous hemianopia. Contrast-enhanced computed tomography showed a giant thrombosed aneurysm on the anterior wall of the ICA located in the optic chiasma. We planned and completed the external carotid artery-middle cerebral artery high-flow bypass using radial artery graft. The visual fields test was performed 14 days after surgery. Homonymous hemianopia persisted but no exacerbation of visual field impairment was observed. No complications were found at 14 days after surgery and the postoperative course was uneventful. Conclusion We consider that external carotid artery-middle cerebral artery bypass surgery using radial artery grafts is a safe and effective treatment method for giant thrombotic aneurysm associated with NF1.

Background: There is currently no established imaging method for assessing liver reserve capacity prior to carbon-ion radiotherapy (CIRT) for liver tumors. In order to perform safe CIRT, it is essential to estimate the post-therapeutic residual reserve capacity of the liver. Purpose: To evaluate the ability of pre-treatment 99m Tc-GSA scintigraphy to accurately estimate the residual liver reserve capacity in patients treated with CIRT for liver tumors. Materials and Methods: This retrospective study evaluated 50 patients who were performed CIRT for liver tumors between December 2018 and September 2020 and underwent 99m Tc-GSA scintigraphy before and 3 months after CIRT, Gd-EOB-DTPA-enhanced MRI within 1 month before CIRT were evaluated. The maximal removal rate of 99m Tc-GSA (GSA-Rmax) was analyzed for the evaluation of pre-treatment liver reserve capacity. Then, the GSA-Rmax of the estimated residual liver (GSA-RL) was calculated using liver SPECT images fused with the Gd-EOB-DTPA-enhanced MRI. GSA-RL before CIRT and GSA-Rmax at 3 months after CIRT were compared using non-parametric Wilcoxon signed-rank test and linear regression analysis. Results: Overall, 50 patients were included (mean age ± standard deviation, 73 years ± 11; range, 29–89 years, 35 men). The median GSA-RL was 0.393 [range, 0.057–0.729] mg/min, the median GSA-Rmax after CIRT was 0.369 [range, 0.037–0.780] mg/min ( P = .40). The linear regression equation representing the relationship between the GSA-RL and GSA-Rmax after CIRT was y = 0.05 + 0.84x (R 2 = 0.67, P < .0001). There was a positive correlation between the estimated and actual post-treatment values for all patients, as well as in the group with impaired liver reserve capacity (y = - 0.02 + 1.09x (R 2 = 0.62, P = .0005)). Conclusions: 99m Tc-GSA scintigraphy has potential clinical utility for estimating the residual liver reserve capacity in patients undergoing carbon-ion radiotherapy for liver tumors. Clinical Trial registration: UMIN000038328, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043545

Purpose:Immune checkpoint inhibitors (ICI) benefit only a minority of treated patients with cancer. Identification of biomarkers distinguishing responders and nonresponders will improve management of patients with cancer. Because the DC-HIL checkpoint differs from the PD1 pathway in expression and inhibitory mechanisms, we examined whether DC-HIL expression regulates ICI responsiveness.Experimental Design:Plasma samples were collected from patients with advanced non–small cell lung carcinoma (NSCLC) (n = 76) at baseline and/or follow-up after ICI monotherapy. Blood-soluble DC-HIL (sDC-HIL) was determined and analyzed for correlation with the early tumor response. To study the mechanisms, we measured effect of anti-DC-HIL versus anti-PDL1 mAb on growth of mouse tumor cells in experimentally metastatic lung. Influence of DC-HIL to anti-PDL1 treatment was assessed by changes in tumor response after deletion of host-DC-HIL gene, injection of DC-HIL–expressing myeloid-derived suppressor cells (MDSC), or induction of sDC-HIL expression.Results:Nonresponders expressed significantly higher levels of baseline sDC-HIL levels than responders. Among patients (n = 28) for fluctuation with time, nonresponders (14/15 cases) showed increasing or persistently elevated levels. Responders (12/13) had decreasing or persistently low levels. Among various tumors, B16 melanoma exhibited resistance to anti-PDL1 but responded to anti-DC-HIL mAb. Using B16 melanoma and LL2 lung cancer, we showed that deletion of host-derived DC-HIL expression converted the resistant tumor to one responsive to anti-PDL1 mAb. The responsive state was reversed by infusion of DC-HIL+MDSC or induction of sDC-HIL expression.Conclusions:sDC-HIL in the blood and probably DC-HIL receptor expressed by MDSC play an important role in regulating response to ICI in advanced NSCLC.

Purpose:Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment.Experimental Design:Patients with metastatic cancer (n = 198) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/lo MDSCs. Their suppressor function was assessed by in vitro coculture with autologous T cells, and the ability of anti-DC-HIL or anti-PDL1 mAb to reverse such function was determined. Tumor expression of these receptors was examined histologically, and the antitumor activity of the mAb was evaluated by attenuated growth of colon cancers in mice.Results:Patients with metastatic cancer had high blood levels of DC-HIL+ MDSCs compared with healthy controls. Anti-DC-HIL mAb reversed the in vitro function in ∼80% of cancer patients tested, particularly for colon cancer. Despite very low expression on blood MDSCs, anti-PDL1 mAb was as effective as anti-DC-HIL mAb in reversing MDSC function, a paradoxical phenomenon we found to be due to upregulated expression of PDL1 by T-cell-derived IFNγ in cocultures. DC-HIL is not expressed by colorectal cancer cells but by CD14+ cells infiltrating the tumor. Finally, anti-DC-HIL mAb attenuated growth of preestablished colon tumors by reducing MDSCs and increasing IFNγ-secreting T cells in the tumor microenvironment, with similar outcomes to anti-PDL1 mAb.Conclusions:Blocking DC-HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC-HIL+ MDSCs.See related commentary by Colombo, p. 453

Supplementary Table S1. Summary of MDSC analysis of metastatic cancer patents. aAll cancer patients are diagnosed as stage III or IV. Supplementary Table S2. Correlation of variables and expansion of DC-HIL+ MDSCs among colorectal cancer patients. Supplementary Table S3. % DC-HIL+ MDSC/PBMC in subgroups with vs. without radiotherapy. Supplementary Table S4. Reversing effects of anti-DC-HIL vs. anti-PDL1 mAb on MDSC suppressor function between two different treatments. Supplementary Table S5. DC-HIL and PDL1 expression in colorectal cancer tissues.

Supplementary Fig. S1. Early stages CRC patients expressed very low DC-HIL expression on MDSCs. Supplementary Fig. S2. No effect of anti-CD14 mAb on T cell suppressor function of MDSCs. Supplementary Fig. S3. DC-HILneg MC38 and CT26 mouse colon cancer cell lines exhibit high response to anti-DC-HIL treatment. Supplementary Fig. S4. MDSCs in spleen and draining lymph nodes did not express DC-HIL. Supplementary Fig. S5. Combination treatment of anti-DC-HIL/anti-PDL1 mAb did not produce synergistic anti-tumor effects to MC38 colon cancer. Supplementary Fig. S6. Changes in health conditions of mice treated with anti-DC-HIL mAb. Supplementary Fig. S7. Representative FACS data showing frequency of immune cells in the tumor microenvironment of mice treated with mAb. Supplementary Fig. S8. Blood granulocytic MDSC of CRC patients expressed low-levels of DC-HIL and were not immunosuppressive in ex vivo cultures.

Figure S1, Figure S2, Figure S3, Figure S4, Figure S5, Figure S6, Figure S7, Figure S8, Table S1, Table S2, Table S3

Painful ganglion cysts that develop in the hallux and finger usually enlarge progressively to the peripheral direction. Simple resection of satellite ganglion cyst alone has been reported to cause a high rate of recurrence and treatment is often very difficult. The purpose of this study is to evaluate the appropriate surgical treatment for painful satellite ganglion cysts in the hallux and finger and discuss the origin of the ganglion cysts in cases treated surgically at our hospital. We reviewed five cases (three males and two females, ages 55–87 years), three of which occurred in the hallux and two in the finger. In all cases, the preoperative magnetic resonance image showed a large fluid of the flexor tendon sheath. And also, joint effusion was found in the metatarsophalangeal joint and the proximal interphalangeal joint. The first case of the hallux ganglion underwent simple excision of the cyst and had recurrences three times. In the other four cases, the additional synovectomy of the metatarsophalangeal joint and the proximal interphalangeal joint was performed along with ganglion cyst excision. These cases had no recurrence up to 1 year after operation. Recently, there have been reports that tendon sheath ganglions are connected to the ankle, wrist, hallux, and phalangeal joints. Although there are a few cases in our department, satellite ganglion cyst of the hallux and finger possibly originates from adjacent joints. Additional synovectomy of the affected joint should be performed for the excision of satellite ganglion cyst to prevent recurrence.

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 0.05). However, administration of MRS2179 failed to improve behavioral outcome. Administration of MRS2179 successfully suppressed microglial activation in a traumatic brain injury model, which will be a potent treatment option in the future. Further study is required to conclude its therapeutic effects.

Background: An open approach is the gold standard for trigger finger (TF) release. However, this may be associated with infection and scar tenderness. Percutaneous trigger release is an alternative, but this can sometimes result in incomplete release and digital nerve injury, even with ultrasound (US) guidance. Limited-open TF release is an intermediate technique that uses a specially designed knife via a 2–3 mm incision. The aim of this study is to compare the outcomes of blinded versus US-guided limited-open TF release using the Yasunaga knife (Medical U&A, Inc., Japan). Methods: About 138 fingers in 111 patients underwent limited-open TF release using the Yasunaga knife. Green classification was used to grade the severity of TF. Thirty-one patients had grade 3 TF and 80 patients had grade 4 TF. The TF was released in a blinded fashion in 60 patients and using US guidance in 51 patients. Outcome measures included residual triggering, contracture of the proximal interphalangeal joint, visual analog scale (VAS) for assessment of pain, Quick Disability of the Arm, Shoulder, and Hand (DASH) score, and the Patel and Moradia grading of patient satisfaction. Complications were also recorded. Results: Six patients had residual triggering in the blinded group, whereas it resolved in all patients in the US-guided group. This difference was statistically significant (p = 0.03). Patients in both groups showed significant improvement in VAS and Quick DASH score postoperatively. There were no significant differences between the two groups for these two outcomes. Patient satisfaction was graded as excellent by 20 patients and good by 30 patients in the US-guided group compared to eight excellent and 45 good in the blinded group. Conclusion: The incidence of residual triggering was lower and overall satisfaction higher in patients who underwent US-guided limited-open TF release using the Yasunaga knife. Level of Evidence: Level III (Therapeutic)

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.

In the closely related Dravidian languages Kuṛux and Malto, the verbs have lexically determined past stems, formed from the verb bases with various suffixes such as -y, -c, -j, -s, -t, -ṭ and -ḍ. There are also past stems with zero, with or without gemination of the final consonant. The past suffixes *-t, *-tt, *-i, *-c, *-cc and *-nt are reconstructed for Proto-Dravidian, and we examined if the Kuṛux-Malto past stems are explainable from them. We found that some past stems are derived from affixation of Proto-Dravidian *-t. The close distributional resemblance of Kuṛux-Malto -y to South Dravidian *-i(ṉ) suggests their common origin. We also confirmed that the suffixes *-c and *-cc need to be posited for Proto-Kuṛux-Malto, while there are no clear reflexes of the suffixes *-tt and *-nt. Since *-c and *-cc are also found in the converb formation of South-Central Dravidian, they might be a shared innovation. The geminating past, which is probably an innovation of Kuṛux-Malto, gave rise to the new, productive past stem class with zero.

A 28-year-old woman experienced severe headache and right homonymous hemianopia after receiving high-dose infliximab for Crohn's disease. Computed tomography showed hemorrhagic infarction in the left temporal and parietal lobes. An angiogram revealed left transverse to sigmoid sinus occlusion and a stagnated Labbe vein. The patient was treated surgically and achieved a good outcome. Inflammatory bowel diseases are known to accompany venous and arterial thrombosis in 1-2% of cases. Recently, infliximab has been suggested to increase this possibility. A case of Crohn's disease presenting with cerebral sinus thrombosis in the remission period during long-term/high-dose use of infliximab is presented. In addition, infliximab-associated thrombosis cases were reviewed.

Introduction Vaginal cuff dehiscence and small bowel evisceration after laparoscopic radical cystectomy, although rare, can be a critical complication. However, little has been reported about it by urologists. Case presentation A 79-year-old woman underwent laparoscopic radical cystectomy for invasive bladder carcinoma. Thirteen months postoperatively, she experienced vaginal cuff dehiscence and small bowel evisceration, and underwent emergency surgery. Intraoperatively, we detached the vaginal apex from the surrounding tissue to lengthen it and performed vaginal uterosacral ligament suspension, with no subsequent recurrence. Conclusion Urologists should pay attention to vaginal cuff dehiscence and small bowel evisceration after laparoscopic radical cystectomy in female patients. In this case, the short vaginal length without vaginal uterosacral ligament suspension might have led to vaginal dehiscence.

Ligand release from silicon phthalocyanine (SiPc) dyes triggered by near-infrared (NIR) light is a key photochemical reaction involving caged compounds based on SiPc. Although NIR light is relatively permeable compared with visible light, this light can be attenuated by tissue absorption and scattering; therefore, using light to induce photochemical reactions deep inside the body is difficult. Herein, because X-rays are highly permeable and can produce radicals through the radiolysis of water, we investigated whether the axial ligands of SiPcs can be cleaved using X-ray irradiation. SiPcs with different axial ligands (alkoxy, siloxy, oxycarbonyl, and phenoxy groups) were irradiated with X-rays under hypoxic conditions. We found that the axial ligands were cleaved

Tolerance towards fetal alloantigens in the maternal immune system is essential for maintaining pregnancy. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their ability to suppress immune activity and maintain maternal-fetal immune tolerance. However, the mechanisms underlying MDSC induction have not been elucidated. Herein, we investigated the myeloid-derived suppressor cells (MDSCs) in the peripheral blood of pregnant canines and its induction mechanism. By analyzing the concentration of MDSCs in the peripheral blood of pregnant canines, elevation of MDSCs has been observed during pregnancy. In addition, MDSCs from pregnant canines inhibit T cell activation. These results suggest that the elevated MDSCs in canine pregnancy may contribute to reduces maternal immune activity. To clarify the cause of MDSCs elevation in canine pregnancy, we analyzed the relationship between pregnancy-related hormones (estradiol, progesterone, and relaxin) and MDSCs. Serum relaxin levels, but not estradiol and progesterone, were correlated with the ratio of monocyte MDSCs. Additionally, relaxin induced monocytic MDSCs as well as inhibited T cell activation in vitro. Therefore, relaxin contributes to the elevation of monocytic MDSCs in the peripheral blood of pregnant canines. Our findings highlight the novel role of relaxin in pregnancy and contribute to a better understanding of maternal-fetal immune tolerance.

Drug metabolizing enzyme activity is affected by various factors such as drug-drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 activity. Iodine-123- and 125-labeled

The link between the coastal ocean and the open sea varies greatly by region. This factor must be elucidated to consider climate projections for a particular coastal region. This study examines this link between coastal areas in Peru and open seas. Water temperature loggers were installed at six sites along the Peruvian coast between 2017 and 2020. The obtained data and that from the EN4 dataset of the open ocean were compared. The coastal water temperature changes in Peru correlates well with the open ocean sea surface temperature in terms of monthly mean anomalies. The correlation coefficient values range from 0.80 to 0.92 with a > 99% confidence level except for one observation point (0.26). This suggests a global ocean observation system underlying EN4 can directly contribute to a reliable climate (water temperature) prediction of coastal areas in Peru. On shorter timescales, the logger-derived temperature changes show spectral peaks at 80 and 120 days north of 5°S, suggesting the coastal monitoring can capture the sub-seasonal dynamical aspects of equatorial Kelvin waves. In contrast, clear peaks are not detected south of 5ºS, implying that a practical leak of equatorial wave energy into off-equatorial regions is not anticipated along Peruvian coast on this time scale.

Invited for this month's cover are the collaborating groups of Yuichi Kitagawa, Yasuchika Hasegawa, Tetsuya Taketsugu, and co-workers at Hokkaido University. The cover picture shows a photosensitizer that has a long excited-state lifetime and provides strong emissions for Tb

Introduction We clarified the renal uptake and urinary secretion mechanism of [99mTc]dimercaptosuccinic acid ([99mTc]DMSA) via drug transporters in renal proximal tubules. Methods [99mTc]DMSA was added to human embryonic kidney 293 cells expressing human multidrug and toxin extrusion (MATE)1 and MATE2-K, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)2; to Flp293 cells expressing human organic anion transporter (OAT)1 and OAT3; and to vesicles expressing P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)2, MRP4, or breast cancer resistance protein with and without probenecid (OAT inhibitor for both OATs and MRPs). Time activity curves of [99mTc]DMSA with and without probenecid were established using LLC-PK1 cells. Biodistribution and single photon emission computed tomography (SPECT) imaging in mice were conducted using [99mTc]DMSA with and without probenecid. Results [99mTc]DMSA uptake was significantly higher in Flp293/OAT3 than in mock cells. Uptake via OAT3 was inhibited by probenecid. [99mTc]DMSA uptake into vesicles that highly expressed MRP2 was significantly higher in adenosine triphosphate (ATP) than in adenosine monophosphate (AMP), and probenecid decreased uptake to similar levels as that in AMP. In the time activity curves for [99mTc]DMSA in LLC-PK1 cells, probenecid loading inhibited accumulation from the basolateral side into LLC-PK1 cells, whereas accumulation from the apical side into cells gradually increased. Transport of [99mTc]DMSA from both sides was low. Biodistribution and SPECT imaging studies showed that [99mTc]DMSA with probenecid loading resulted in significantly higher accumulation in blood, heart, liver, and bladder after [99mTc]DMSA injection compared with control mice. Probenecid induced significantly lower accumulation in the kidney after [99mTc]DMSA injection. Conclusions [99mTc]DMSA accumulates in renal proximal tubular epithelial cells from blood via OAT3 on the basolateral side, and then a small volume of [99mTc]DMSA will be excreted in urine via MRP2. Advances in knowledge [99mTc]DMSA accumulates via OAT3 in renal proximal tubular epithelial cells and is slightly excreted from the cells via MRP2. Implications for patient care [99mTc]DMSA may be useful for measuring renal transport function with OAT3 in patients.

The World Health Organization has cautioned that antimicrobial resistance (AMR) will be responsible for an estimated 10 million deaths annually by 2050. To facilitate prompt and accurate diagnosis and treatment of infectious disease, we investigated the potential of amino acids for use as indicators of bacterial growth activity by clarifying which amino acids are taken up by bacteria during the various growth phases. In addition, we examined the amino acid transport mechanisms that are employed by bacteria based on the accumulation of labeled amino acids, Na+ dependence, and inhibitory effects using a specific inhibitor of system A. We found that 3H-L-Ala accurately reflects the proliferative activity of Escherichia coli K-12 and pathogenic EC-14 in vitro. This accumulation in E. coli could be attributed to the amino acid transport systems being different from those found in human tumor cells. Moreover, biological distribution assessed in infection model mice with EC-14 using 3H-L-Ala showed that the ratio of 3H-L-Ala accumulated in infected muscle to that in control muscle was 1.20. By detecting the growth activity of bacteria in the body that occurs during the early stages of infection by nuclear imaging, such detection methods may result in expeditious diagnostic treatments for infectious diseases.

A scheme to automatically determine the buffer region in the divide-and-conquer (DC) large-scale quantum chemical method is introduced. The butler region directly relates to the error introduced by the DC method. In the iterative DC Hartree-Fock procedure, the automatic scheme adopts two-layered buffer region and gradually enlarges the buffer region by evaluating the energy contribution from the outer buffer region and determining whether the buffer region should be enlarged or not based on the energy-based threshold. On the other hand, in the non-iterative DC second-order Moller-Plesset perturbation calculation, the energy contribution is approximately estimated for the atoms in the buffer region and only those atoms that contribute more than an energy-based threshold are left in the buffer region. We demonstrated that both methods achieve almost constant accuracy in the energy using only one energy-based threshold as a parameter.

Introduction Neovascular glaucoma is characterized by neovascularization of the iris and the anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may improve intraocular pressure (IOP) and neovascularization. Methods The VEGA trial assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma in a 13-week, randomized, double-masked, sham-controlled, phase 3 study performed at multiple sites in Japan that enrolled patients with anterior segment neovascularization and IOP > 25 mmHg. Patients received background therapy plus IVT-AFL (2 mg) or sham injection at baseline. Patients were re-treated if presenting with IOP > 21 mmHg and incomplete regression of iris neovascularization, receiving additional sham or IVT-AFL injections at week 1 and IVT-AFL injections at weeks 5 and/or 9. Double-masking was maintained throughout. The primary endpoint was change in IOP from baseline to week 1. Results Fifty-four patients were randomly assigned (full analysis set); the per-protocol set comprised 52 patients. At week 1, the least squares mean change in IOP was −9.9 mmHg for IVT-AFL versus −5.0 mmHg for sham [full analysis set: difference −4.9 mmHg (95% confidence interval −10.2 to 0.3; P = 0.06); per-protocol set: −5.5 mmHg (95% CI −10.8 to −0.2; P = 0.04)]. At week 1, a greater proportion of patients administered IVT-AFL versus sham achieved IOP ≤ 21 mmHg and had improved neovascularization grades. Patients in the sham group who met re-treatment criteria and received IVT-AFL at week 1 [n = 22 (81.5%)] had an additional mean IOP decrease of 9.2 mmHg by week 2, and the proportion with improvement in neovascularization grades increased from 11.5% to 69.2%. Increases in the proportion of patients with improved neovascularization grades and the proportion who achieved IOP control (≤ 21 mmHg) were also observed by week 2 in this group. Overall, 77.8% and 74.1% of patients treated with IVT-AFL and sham/IVT-AFL, respectively, received a single IVT-AFL injection. The most common ocular treatment-emergent adverse event was punctate keratitis (9.3%: 7.4% and 11.1% in the IVT-AFL and sham/IVT-AFL groups, respectively). Conclusions IVT-AFL was associated with clinically meaningful improvements in IOP control, indicating that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. Trial Registration Clinicaltrials.gov identifier, NCT02396316. Electronic supplementary material The online version of this article (10.1007/s12325-020-01579-5) contains supplementary material, which is available to authorized users.

A chiral Eu(III) coordination polymer with phase-transition behavior, [Eu(+tfc)3(m-dpeb)]n, (+tfc: (+)-3-trifluoroacetylcamphorato, m-dpeb: 1,3-bis(diphenylphosphorylethynyl)benzene) was reported for understanding the effect of polymer chain arrangement (orientation effect) on the circularly polarized luminescence (CPL) in a solid system. The phase-transition behavior of the transformable Eu(III) coordination polymer was characterized using differential scanning calorimetry and powder X-ray diffraction. The Eu(III) coordination polymer exhibited phase transition at approximately 180 degrees C. The magnitude of the CPL intensity was drastically changed because of the phase transition, without coordination geometrical change around the Eu(III) ion. In this study, the orientation effect of a chiral Eu(III) coordination polymer on the CPL properties in crystalline solid is demonstrated.

There is currently no established imaging method for assessing liver reserve capacity prior to carbon-ion radiotherapy (CIRT) for liver tumors. In order to perform safe CIRT, it is essential to estimate the post-therapeutic residual reserve capacity of the liver.To evaluate the ability of pre-treatmentThis retrospective study evaluated patients who were performed CIRT for liver tumors between December 2018 and September 2020 and underwentOverall, 50 patients were included (mean age ± standard deviation, 73 years ± 11; range, 29-89 years, 35 men). The median GSA-RL was 0.393 [range, 0.057-0.729] mg/min, and the median GSA-Rmax after CIRT was 0.369 [range, 0.037-0.780] mg/min (P = .40). The linear regression equation representing the relationship between the GSA-RL and GSA-Rmax after CIRT was y = 0.05 + 0.84x (RUMIN000038328, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043545 .