Understanding Flexdispersion: Structure-Function Relationship Studies of Organic Amphiphilic Ligands.

Since inorganic nanoparticles have unique properties that differ from bulk materials, their material applications have attracted attention in various fields. In order to utilize inorganic nanoparticles for functional materials, they must be dispersed without agglomeration. Therefore, the surfaces of inorganic nanoparticles are typically modified with organic ligands to improve their dispersibility. Nevertheless, the relationship between the tail group structure in organic ligands and the dispersibility of inorganic nanoparticles in organic solvents remains poorly understood. We previously developed amphiphilic ligands that consist of ethylene glycol chains and alkyl chains to disperse inorganic nanoparticles in a variety of organic solvents. However, the structural requirements for amphiphilic ligands to "flexibly" disperse nanoparticles in less polar to polar solvents are still unclear. Here, we designed and synthesized several phosphonic acid ligands for structure‒function relationship studies of flexdispersion. Dynamic light scattering analysis and visible light transmittance measurements revealed that the ratio of alkyl/ethylene glycol chains in organic ligands alone does not determine the dispersibility of the nanoparticles in organic solvents, but the arrangement of the individual chains also has an effect. From a practical application standpoint, it is preferable to design ligands with ethylene glycol chains on the outside relative to the particle surface.

Feasibility Study of Transarterial Chemotherapy Followed by Chemoembolization for Recurrent Breast Cancer.

PURPOSE: To assess the treatment response to transarterial chemotherapy followed by chemoembolization for locally recurrent breast cancer. MATERIALS AND METHODS: Thirty-nine women with locally recurrent breast cancer after standard therapy underwent selective intra-arterial chemotherapy followed by embolization using drug-eluting microspheres for locally recurrent tumors and axillary lymph node metastases. Tumor response and toxicity were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and Common Terminology Criteria for Adverse Events (CTCAE), and survival was evaluated by the Kaplan‒Meier method. RESULTS: The local responses of breast tumors at 3 and 6 months were as follows: complete response, 5.1% and 7.2%; partial response, 35.9% and 67.8%; stable disease, 59.0% and 21.4%; and progressive disease, 0.0% and 3.6%, respectively. All adverse events were mild and did not require treatment. The median overall survival (OS) was 46.5 months, and the OS rates for 1 and 2 years were 81.4% and 69.2%, respectively. The size of recurrent tumors and axillary lymph node metastases did not impact prognosis, but both liver and bone metastases adversely affected survival. CONCLUSION: Transarterial chemotherapy followed by chemoembolization may provide a favorable tumor response in patients with locally recurrent breast cancer in whom conventional therapy has failed.

High Cathode Loading and Low-Temperature Operating Garnet-Based All-Solid-State Lithium Batteries - Material/Process/Architecture Optimization and Understanding of Cell Failure.

All-solid-state lithium batteries (ASSLBs) are prepared using garnet-type solid electrolytes by quick liquid phase sintering (Q-LPS) without applying high pressure during the sintering. The cathode layers are quickly sintered with a heating rate of 50-100 K min-1 and a dwell time of 10 min. The battery performance is dramatically improved by simultaneously optimizing materials, processes, and architectures, and the initial discharge capacity of the cell with a LiCoO2 -loading of 8.1 mg reaches 1 mAh cm-2 and 130 mAh g-1 at 25 °C. The all-solid-state cell exhibits capacity at a reduced temperature (10 °C) or a relatively high rate (0.1 C) compared to the previous reports. The Q-LPS would be suitable for large-scale manufacturing of ASSLBs. The multiphysics analyses indicate that the internal stress reaches 1 GPa during charge/discharge, which would induce several mechanical failures of the cells: broken electron networks, broken ion networks, separation of interfaces, and delamination of layers. The experimental results also support these failures.

Successful control of a large intrahepatic cholangiocarcinoma treated by transarterial chemo-embolization; a single case report.

Intrahepatic cholangiocarcinoma is hardly diagnosed in early stages as the symptoms are non-specific. Due to an advanced stages at the time of first diagnosis, the therapeutic options for patients with unresectable cholangiocarcinoma are mostly limited to systemic chemotherapy or radiotherapy, but good local control or preferable prognostic effects are hardly obtained. The transarterial chemoembolization had not been a standard of care because of hepatic functional damages caused by lipiodol and gelatin sponge. A newly developed spherical embolic material causes limited hepatic damages might be an option for these patients. It makes it possible to repeat the procedure in a short period. Eventually, better prognosis can be expected using a spherical embolic material. We report a case of a 15 cm locally advanced intrahepatic cholangiocarcinoma treated by chemoembolization using a drug-eluting spherical embolic material and achieved good local tumor control without liver damage. The patient survived longer than 4 years without additional or concomitant treatments.

Transarterial Treatment of Lung Cancer.

PURPOSE: The treatment efficacy of the transarterial approach to lung cancer is evaluated. MATERIALS AND METHODS: A total of 98 patients with advanced lung cancer or recurrent lung cancer after the standard therapies were enrolled retrospectively. The bronchial arteries and mediastinal branches from the subclavian artery were selected by a microcatheter. Immediately after the selective arterial infusion of anti-neoplastic agents, embolization with a spherical embolic material was carried out. Local tumor effects and overall survival were evaluated. RESULT: The mean reduction rate was 17.9%, with 24.2% for partial remission and with 2.1% for progression disease. The rate of stable disease was 72.6%. The response rate was 25.3%, and the disease control rate was 97.9%. The median survival time (MST) was 11.4 months, the 1-year survival rate was 45.2%, and the 2-year survival rate was 35.6%. Although it is insignificant, the MST for 51 adenocarcinomas was higher than that of 29 squamous cell carcinomas (18.6 months and 9.4 months, respectively). The local extension of tumors related to a better prognosis, though it was not significant. Lymph node metastases and distant metastases were poor prognostic factors. No major complications nor treatment-related mortalities were found in this study. CONCLUSION: The transarterial treatment for lung cancer should be considered as a treatment option when the other treatments were not indicated both in initial cases and in recurrent cases.

Combined Use of Reducing Agents and Biodegradable Chelating Agent for Iron Rust Removal.

Since many of the current chemicals used to remove iron rust are hazardous to the environment and human health, the combined use of a reducing agent and a biodegradable chelating agent has been suggested as an environmental friendly and highly safe alternative. In the present work, the compatibility of the newly devised cleaning test with a model iron rust stain was confirmed by X-ray diffraction and scanning electron microscopy. Additionally, the cleaning efficiency of the method was evaluated by X-ray fluorescence. The cleaning mechanism and the synergistic effect of the reducing agent and the chelating agent was investigated using the phenanthroline absorption measurement method, and the results revealed that the reduced iron ions were dissolved by the chelating agent. The cleaning test proved that tetrasodium 3-hydroxy-2,2'-iminodisuccinate (HIDS) is a promising biodegradable chelating agent as an alternative to ethylenediaminetetraacetic acid (EDTA) for removing iron rust. It was also confirmed that the type of reducing agent used determines the pH at which detergency is enhanced. The detergency of the combination of the reducing agent and the biodegradable chelating agent was equal to or higher than the detergency of the acid agent, and thus, it was concluded that the proposed method has a great potential for commercial use.

[Transarterial Chemoembolization for Unresectable Gastric Cancer in the Esophago-Gastric Junction-A Case Report].

A case of extensive esophageal stenosis and bleeding caused by advanced gastric cancer in esophago-gastric junction treated by the transarterial chemoembolization(TACE)was reported. After standard systemic chemotherapy and radiotherapy, TACE was introduced to control these symptoms. A microcatheter was successfully advanced to the left gastric artery and esophageal artery arising from the thoracic aorta. The blood supply to the lesion was confirmed by CT scan during contrast injection through the microcatheter. The drugs were 5-FU 250 mg/body, cisplatin 20 mg/body, docetaxel 20 mg/body and bevacizumab 100 mg/body. Embolic material was HepaSphereTM(50-100µm). The patient survived one and half years without dysphagia and bleeding. TACE for extensive esophageal stenosis caused by advanced gastric cancer can be a treatment option to control tumor growth and bleeding.

Evaluation of the VITEK2 AST-XN17 card for the detection of carbapenemase-producing Enterobacterales in isolates primarily producing metallo ß-lactamase.

Carbapenemase-producing Enterobacterales (CPE) are not always resistant to carbapenem antimicrobial susceptibility testing (AST) and can be difficult to detect. With the newly created VITEK2 AST-XN17 card, the types of antibiotics measured in AST can be increased. In this study, we evaluated the detectability of CPE using the results of AST with multiple antimicrobial agents with additional measurements of the AST-XN17 card. In addition, we evaluated the CPE detectability of comments on CPE using the VITEK2 Advance Expert System (AES). In total, 169 Enterobacterales samples, including 76 non-CPE and 93 CPE, collected from multiple medical institutions in the Kinki region of Japan, were used in this investigation. AST with VITEK2 was performed by adding the AST-XN17 card in addition to the AST-N268 or AST-N404 card. Measurement results were identified using cutoff values, primarily Clinical and Laboratory Standards Institute breakpoints, and the CPE detection capability of each antibiotic was evaluated in several terms, including sensitivity and specificity. The drugs highly sensitive to CPE detection were faropenem (FRPM) > 2 µg/mL at 100% and meropenem > 0.25 µg/mL at 98.9%; the highest specificity to CPE detection was for avibactam/ceftazidime (AVI/CAZ) > 8 µg/mL at 100%. The sensitivity and specificity of each card in the AES output were 86.2% and 94.7% for AST-N404 and AST-XN17 and 91.5% and 90.8% for AST-N268 and AST-XN17, respectively. AST using the VITEK2 AST-XN17 card is a useful test method of screening for CPE.

A large fraction of trisomy 12, 17p-, and 11q- CLL cases carry unidentified microdeletions of miR-15a/16-1.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by chromosomal aberrations including 13q, 11q, and 17p deletions and a trisomy of chromosome 12 (T12). 13q deletions are often associated with 11q and 17p deletions in aggressive cases. Conversely, T12 CLLs show a variable prognosis, and association with 13q deletions is uncommon. The miR-15a/16-1 cluster is the functional target of 13q deletions, leading to BCL2 overexpression. Chromosomal aberrations in CLL are associated with prognosis, and their identification is carried out by fluorescence in situ hybridization (FISH). Since standard FISH only detects large deletions, we investigated the presence of undetected microdeletions targeting miR-15a/16-1 in CLL cases. We found that ∼34% of CLL samples show an unreported loss of the miR-15a/16-1 locus regardless of their cytogenetic profile. Interestingly, 15 out of 39 (∼39%) of all CLLs with T12, carry microdeletions of miR-15a/16-1, indicating that, in patients with T12, miR-15a/16-1 are mostly inactivated by microdeletions. In addition, ∼40% of CLL cases bearing T12, 17p-, and 11q- showed unidentified microdeletions of miR-15a/16-1, suggesting that miR-15a/16-1 loss cooperates with such chromosomal alterations in CLL. These data may have clinical relevance for the successful stratification of patients for treatment.

Oral support for patients with severe motor and intellectual disabilities.

BACKGROUND: Oral support during feeding was clinically provided to patients with severe motor and intellectual disabilities (SMID) for the prevention of dysphasia. The present study investigated the advantages of oral support anatomically and functionally. METHODS: A videofluoroscopic swallowing study was conducted on nine patients with SMID (age = 5-41 years; mean age = 15.0; four males, five females) and 24 healthy adults (age = 26-67 years; mean age = 44.3; 16 males, eight females). The movements of the hyoid bone and mandible during pharyngeal swallowing were tracked, and the pharyngeal residues were evaluated. The temporal and spatial features of the movements were compared between patients with and without oral support as well as healthy adults. RESULTS: The mandible moved downward earlier and showed larger displacement in the patients with SMID. The patients also had insufficient anterior displacement of the hyoid, which was associated with the pharyngeal residue. This displacement was enhanced, and the pharyngeal residue decreased with oral support. CONCLUSIONS: Oral support to hold the mandible successfully improved hyoid excursion and reduced pharyngeal residue during swallowing, which is a simple and reliable strategy for the prevention of dysphasia in patients with SMID.

[Microsphere TACE with Arterial Infusion of Bevacizumab for Portal Vein Tumor Thrombus by Hepatocellular Carcinoma].

The successful treatment of 2 cases of portal vein tumor thrombus caused by hepatocellular carcinoma was reported. It is difficult to manage portal vein tumor thrombi by conventional transarterial chemoembolization(c-TACE)using lipiodol and a gelatin sponge. On the other hand, drug-eluting-microsphere TACE(DEM-TACE)can preserve hepatic function by maintaining the capillary circulation of sinusoids and the peribiliary arterial plexus. Even in cases of portal vein tumor thrombus, DEM-TACE could be safely performed without hepatic infarction. Bevacizumab, anti-VGEF monoclonal antibody, was injected into hepatic arteries with anti-neoplastic agents, followed by the epirubicin-loaded superabsorbent polymer microsphere( HepaSphere). The tumor thrombi in 2 cases were successfully eliminated after treatment for more than 2 years without deterioration of the hepatic function.

Genomic Characterization of ESBL- and Carbapenemase-Positive Enterobacteriaceae Co-harboring mcr-9 in Japan.

Worldwide spread of Enterobacteriaceae resistant to colistin, a polypeptide antibacterial drug for last-resort treatment of carbapenemase-producing Enterobacteriaceae (CPE) infections, is concerning. This study aimed to elucidate colistin MICs and molecular characteristics of mcr-1 to mcr-9 of ESBL-producing Escherichia coli (ESBL-Ec) and CPE in Japan and clarify the genomic structure of strains harboring mcr genes (especially mcr-9). This study included 168 ESBL-Ec and 126 CPE strains isolated at Japanese medical facilities. Colistin susceptibility testing and multiplex PCR targeting mcr-1 to mcr-9 were performed for all strains with S1-nuclease pulsed-field gel electrophoresis, Southern blot hybridization, and whole-genome sequencing (WGS) with hybrid assembly performed for mcr gene-carrying strains. Two CPE strains showed a MIC ≥ 4 µg/ml in colistin susceptibility testing, with no known resistance mechanism detected. However, PCR conducted on all target strains detected three mcr-9-carrying strains showing colistin susceptibility. The bla CTX-M-62 -positive E. coli THUN648 strain simultaneously carried bla CTX-M-62 and mcr-9 on a 275-kbp plasmid. Besides, bla IMP-6 + bla CTX-M-2 -positive Klebsiella pneumoniae THUN262 and bla GES-24 -positive Enterobacter kobei THUN627 had mcr-9 encoded on the chromosome. Only THUN627 encoded qseB/C, which is suggested to be a regulatory gene for mcr-9, downstream of mcr-9. However, this strain showed no increased expression of these genes in mRNA quantitative analysis under colistin exposure. Colistin MICs of ESBL-Ec and CPE in Japan were all below 2 µg/ml, which is below the epidemiological cutoff (ECOFF) value (https://eucast.org/) or clinical breakpoint (CB) (CLSI M100-S30) reported for colistin, indicating neither "microbiological" nor "clinical" resistance. Several colistin-susceptible Enterobacteriaceae carrying silent mcr-9 encoded on plasmids and chromosomes have already spread worldwide along with other antimicrobial resistance genes. However, the mechanism of colistin resistance by mcr-9 remains unclear.

Comparison of the performance of three carbapenem inactivation methods for the detection of carbapenemase-producing gram-negative bacilli.

INTRODUCTION: The carbapenem inactivation method test (CIM) was developed as a method for detecting carbapenemase-producing Gram-negative bacilli, and the modified CIM (mCIM) was recommended by the CLSI for as an improved method in M100-S27. However, few studies have evaluated the influence of bacterial species and genotype on its sensitivity and specificity. In this study, we evaluate the performance of these improved modified CIM methods with mCIM. METHODS: As strains, clinical isolates from Naga Municipal Hospital and stored strains from the Study of Bacterial Resistance in the Kinki Region of Japan were used. The mCIM, CIM-Tris, and simple CIM (sCIM) test methods were applied to 120 Enterobacterales, 40 Pseudomonas aeruginosa, and 37 Acinetobacter spp. The procedure and criteria for each method were based on the original papers and the CLSI M - 100 S27 documents. RESULTS: The sensitivity of the test methods in the detection of carbapenemase in Enterobacterales, Pseudomonas spp., and Acinetobacter spp. was as follows: mCIM, 98.9%, 90.0%, and 76.5%, respectively; CIM-Tris, 94.4%, 100%, 100%; and sCIM 98.9%, 85.0%, 76.5%. All methods showed 100% specificity in Enterobacterales, Pseudomonas spp., and Acinetobacter spp. Each method performed well in the detection of metallo ß-lactamase-producing strains, however, the sensitivity tended to be low in the detection of the organisms producing serine-type carbapenemase, such as GES, OXA-23, and OXA-51. CONCLUSIONS: Care must be taken when selecting test methods because the sensitivity of the detection differs depending on the bacterial species and genotype.

Hyoid bone movement during swallowing and mechanism of pharyngeal residue in patients with profound intellectual and multiple disabilities.

OBJECTIVES: Dysphagia is linked to mortality risk among patients with profound intellectual and multiple disabilities (PIMD); the present study therefore aimed to clarify the characteristics of hyoid movements during swallowing and to examine the mechanism of dysphagia in patients with PIMD. METHODS: A retrospective video fluoroscopic swallowing study was conducted on 43 patients with PIMD (mean age = 25.4; 25 males, 18 females) and 24 healthy adults (mean age = 44.3; 16 males, 8 females). The movements of the hyoid bone and mandible were tracked frame by frame in the video footage, and their range of movements and trajectories were analyzed. RESULTS: Most patients showed atypical movement trajectories of the hyoid, such as insufficient anterior movement and increased range of mandibular downward movement, compared with normal adults. Moreover, the mechanism of dysphagia was revealed by structural equation modeling, indicating that insufficient anterior movement could lead to pharyngeal residue in the pyriform sinus. CONCLUSION: The insufficient anterior movement of the hyoid could be caused by weak ventral suprahyoid muscles and atypical head and neck posture characteristic of patients with PIMD. It may be useful to predict pharyngeal residue from the range of hyoid movements and trajectories for the prevention of aspiration.

Transarterial management of advance lung cancer.

Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control with less doses of anti-neoplastic agents was warranted by trying transarterial administration to lung and mediastinal tumors. It is reported that both primary and metastatic tumors are fed by bronchial or other systemic arteries. The bronchial arterial embolization for hemoptysis has been introduced for clinical practice since 1973. Hemoptysis by not only benign but also malignant diseases has been well controlled by embolization. In recent decades, the technical elements for transarterial treatments have markedly improved. They make it possible to carry out precise procedures of selective catheter insertion to the tumor relating arteries. Current concepts of transarterial treatment, technical aspects and treatment outcomes are summarized. Tentative result from chemo-embolization for advanced lung cancer using recent catheter techniques was also described. It provides favorable local control and survival merits. It is considered that a population of lung cancer patients can benefit from transarterial management using small doses of anti-neoplastic agents, with less complications and less medical costs.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

BACKGROUND AND PURPOSE: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. MATERIALS AND METHODS: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). RESULTS: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). CONCLUSION: These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

The microcolony detection method (MCD), a simple and rapid screening test for antimicrobial resistance bacteria on positive blood cultures.

Rapid detection of antibiotic-resistant bacteria in blood cultures is critical for the timely treatment of patients with sepsis. The aim of this study was to develop a simple method for the rapid detection of drug-resistant bacteria from blood cultures and to evaluate its performance. We developed an optical microscopy-based microcolony detection method (MCD) for the rapid detection of antibiotic-resistant bacterial colonies in media. This method was tested using staphylococci resistant to methicillin and gram-negative bacilli resistant to third-generation cephalosporins and carbapenem. The results of the investigations of clinical samples using this method were compared with the drug susceptibility testing results for each of the 457 isolates, which included 134 staphylococci and 323 g-negative bacilli. The MCD was successful in detecting antibiotic-resistant bacterial growth from culture-positive blood samples in approximately 3 h. The sensitivity/specificity for methicillin-resistant staphylococci was 100%/97.2%. In the case of gram-negative bacilli, the sensitivity/specificity values for bacteria resistant to ceftriaxone, ceftazidime, and carbapenem were 100%/98.7%, 100%/89.3%, and 100%/90.9%, respectively. Therefore, MCD is a clinically useful screening method for the efficient and rapid detection of antibiotic-resistant bacteria and can be easily implemented in laboratories.

Proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for an extremely rapid growing recurrent ameloblastic carcinoma: A case report.

Ameloblastic carcinoma (AC) is a very rare malignant odontogenic tumor. Although surgical resection is generally performed, treatment approaches have not been established for recurrent cases. Chemotherapy and radiotherapy are positioned as adjunctive therapies, and few studies investigated definitive non-operative therapy. We present the case of a 71-year-old male with recurrent secondary-type AC arising from the right maxilla, who was treated with proton beam therapy (PBT; 71.4 Gy relative biological effectiveness in 32 fractions) combined with continuous intra-arterial infusion of cisplatin (40 mg/m2) and docetaxel (8 mg/m2). The patient experienced acute grade 3 mucositis, dermatitis and neutropenia, which were resolved within 3 months of treatment. Late adverse events were grade 1 skin atrophy, and grade 2 right optic nerve disorder and retinopathy. After ~8 years of treatment, the patient died from another cause but did not experience any relapse or metastasis during the follow-up period of 94 months. To the best of our knowledge, this is the first report of recurrent AC treated with PBT and intra-arterial infusion chemotherapy without any severe late adverse events. This combination therapy approach may be considered as an effective therapeutic option for inoperable AC.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Gastric Cancer with Mediastinal Lymph Node Metastases Causing Esophageal Compression and Dysphagia-A Case Report].

A 50s man was diagnosed with esophagogastric junction cancer. Simultaneously, PET-CT demonstrated mediastinal lymph node metastases. Two months later, 4 courses of systemic chemotherapy(SOX)were provided as preoperative therapy. However, the outcome was PD; therefore, radical gastrectomy could not be performed. Two more months later, esophageal dysphagia developed. Mediastinal lymph nodes that compressed the esophagus and the primary lesion of the cardia were considered to be the causes of dysphagia, and transcatheter arterial chemoembolization targeting those 2 lesions was performed. Cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250mg were the drugs administered. These drugs were injected from the right bronchial artery, left gastric artery, and left phrenic artery, followed by mild embolization with HepaSphereTM. The mediastinal lymph nodes shrunk significantly, and dysphagia improved with 2 sessions. The primary lesion was found to have reduced in size with 6 sessions. Currently, no regrowth of the mediastinal lymph nodes has been observed 16 months(9 sessions) after the first session, and control of the primary lesion has been obtained.