[Side Effect Management in the Early Stages of Cabozantinib Administration].

In 2 patients with postoperative lung metastases from renal cell carcinoma, we administered cabozantinib at a starting dose of 40 mg. The side effects were proteinuria(Grade 2), hand-foot syndrome(Grade 2), and hypertension(Grade 3), which subsided following dose reduction and drug suspension. We believe that a low starting dose of cabozantinib might be a suitable regimen for advanced renal cell carcinoma.

[Evaluation of Risk Factors for Immune-Related Adverse Events Associated with Treatment with Immune Checkpoint Inhibitors].

OBJECTIVE: Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs. METHODS: The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group). RESULTS: The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer. CONCLUSION: At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.

Biotic manganese oxidation coupled with methane oxidation using a continuous-flow bioreactor system under marine conditions.

Biogenic manganese oxides (BioMnOx) can be applied for the effective removal and recovery of trace metals from wastewater because of their high adsorption capacity. Although a freshwater continuous-flow system for a nitrifier-based Mn-oxidizing microbial community for producing BioMnOx has been developed so far, a seawater continuous-flow bioreactor system for BioMnOx production has not been established. Here, we report BioMnOx production by a methanotroph-based microbial community by using a continuous-flow bioreactor system. The bioreactor system was operated using a deep-sea sediment sample as the inoculum with methane as the energy source for over 2 years. The BioMnOx production became evident after 370 days of reactor operation. The maximum Mn oxidation rate was 11.4 mg L-1 day-1. An X-ray diffraction analysis showed that the accumulated BioMnOx was birnessite. 16S rRNA gene-based clone analyses indicated that methanotrophic bacterial members were relatively abundant in the system; however, none of the known Mn-oxidizing bacteria were detected. A continuous-flow bioreactor system coupled with nitrification was also run in parallel for 636 days, but no BioMnOx production was observed in this bioreactor system. The comparative experiments indicated that the methanotroph-based microbial community, rather than the nitrifier-based community, was effective for BioMnOx production under the marine environmental conditions.

Spatially Resolved Distribution of Fe Species around Microbes at the Submicron Scale in Natural Bacteriogenic Iron Oxides.

Natural bacteriogenic iron oxides (BIOS) were investigated using local-analyzable synchrotron-based scanning transmission X-ray microscopy (STXM) with a submicron-scale resolution. Cell, cell sheath interface (EPS), and sheath in the BIOS were clearly depicted using C-, N-, and O- near edge X-ray absorption fine structure (NEXAFS) obtained through STXM measurements. Fe-NEXAFS obtained from different regions of BIOS indicated that the most dominant iron mineral species was ferrihydrite. Fe(II)- and/or Fe(III)-acidic polysaccharides accompanied ferrihydrite near the cell and EPS regions. Our STXM/NEXAFS analysis showed that Fe species change continuously between the cell, EPS, and sheath under several 10-nm scales.

Comparative Analysis of Microbial Communities in Iron-Dominated Flocculent Mats in Deep-Sea Hydrothermal Environments.

UNLABELLED: It has been suggested that iron is one of the most important energy sources for photosynthesis-independent microbial ecosystems in the ocean crust. Iron-metabolizing chemolithoautotrophs play a key role as primary producers, but little is known about their distribution and diversity and their ecological role as submarine iron-metabolizing chemolithotrophs, particularly the iron oxidizers. In this study, we investigated the microbial communities in several iron-dominated flocculent mats found in deep-sea hydrothermal fields in the Mariana Volcanic Arc and Trough and the Okinawa Trough by culture-independent molecular techniques and X-ray mineralogical analyses. The abundance and composition of the 16S rRNA gene phylotypes demonstrated the ubiquity of zetaproteobacterial phylotypes in iron-dominated mat communities affected by hydrothermal fluid input. Electron microscopy with energy-dispersive X-ray microanalysis and X-ray absorption fine structure (XAFS) analysis revealed the chemical and mineralogical signatures of biogenic Fe-(oxy)hydroxide species and the potential contribution of Zetaproteobacteria to the in situ generation. These results suggest that putative iron-oxidizing chemolithoautotrophs play a significant ecological role in producing iron-dominated flocculent mats and that they are important for iron and carbon cycles in deep-sea low-temperature hydrothermal environments. IMPORTANCE: We report novel aspects of microbiology from iron-dominated flocculent mats in various deep-sea environments. In this study, we examined the relationship between Zetaproteobacteria and iron oxides across several hydrothermally influenced sites in the deep sea. We analyzed iron-dominated mats using culture-independent molecular techniques and X-ray mineralogical analyses. The scanning electron microscopy-energy-dispersive X-ray spectroscopy SEM-EDS analysis and X-ray absorption fine structure (XAFS) analysis revealed chemical and mineralogical signatures of biogenic Fe-(oxy)hydroxide species as well as the potential contribution of the zetaproteobacterial population to the in situ production. These key findings provide important information for understanding the mechanisms of both geomicrobiological iron cycling and the formation of iron-dominated mats in deep-sea hydrothermal fields.

[Team Approaches for and Future Challenges to Promoting Perioperative Oral Management].

When the medical fee system was revised in 2012, the category of perioperative oral management was newly organized. However, the calculation of additional fees for such management required referral from medical to dental departments. In addition, requests for such management were limited, possibly owing to an increased burden on doctors engaged in outpatient services. This study examined the usefulness of an approach to promote patients' use of dental services by increasing their awareness of the importance of oral management. In this approach, pharmacists explained doctors' instructions to patients at a chemotherapy center within the study facility. Explanations were provided to 114 patients, 75 (65.8%) of whom subsequently used dental services in the facility. For patients using dental services, oral care was performed most frequently (40; 53.3%), followed by invasive procedures (23; 30.7%). Furthermore, the facility's ethics committee approved a survey to measure the satisfaction of patients undergoing chemotherapy at the center. Of the 110 patients invited to participate in the survey, 77(70.0%) did not respond. Researchers concluded the low response rate was associated with patients' belief that dental services were intended primarily for treating oral cavities and their lack of awareness of the importance of preventive dental care. However, in 2014, the number of calculations of additional fees for perioperative oral management markedly increased each month after the above-mentioned approach, from 62 (January) to 162 (December). Both the hospital-to family and family-to-hospital dentist referral rates significantly increased, from 11.2% and 10.7%, respectively (June 2013), to 21.0% and 41.9%, respectively(June 2014). Future evaluations of the outcomes of perioperative oral management and promoting cooperation between medical and dental communities may be necessary.

Electrical characteristic of the titanium mesh electrode for transcutaneous intrabody communication to monitor implantable artificial organs.

We have developed a tissue-inducing electrode using titanium mesh to obtain mechanically and electrically stable contact with the tissue for a new transcutaneous communication system using the human body as a conductive medium. In this study, we investigated the electrical properties of the titanium mesh electrode by measuring electrode-tissue interface resistance in vivo. The titanium mesh electrode (Hi-Lex Co., Zellez, Hyogo, Japan) consisted of titanium fibers (diameter of 50 µm), and it has an average pore size of 200 µm and 87 % porosity. The titanium mesh electrode has a diameter of 5 mm and thickness of 1.5 mm. Three titanium mesh electrodes were implanted separately into the dorsal region of the rat. We measured the electrode-electrode impedance using an LCR meter for 12 weeks, and we calculated the tissue resistivity and electrode-tissue interface resistance. The electrode-tissue interface resistance of the titanium mesh electrode decreased slightly until the third POD and then continuously increased to 75 Ω. The electrode-tissue interface resistance of the titanium mesh electrode is stable and it has lower electrode-tissue interface resistance than that of a titanium disk electrode. The extracted titanium mesh electrode after 12 weeks implantation was fixed in 10 % buffered formalin solution and stained with hematoxylin-eosin. Light microscopic observation showed that the titanium mesh electrode was filled with connective tissue, inflammatory cells and fibroblasts with some capillaries in the pores of the titanium mesh. The results indicate that the titanium mesh electrode is a promising electrode for the new transcutaneous communication system.

Measurement of electrode-tissue interface impedance for improvement of a transcutaneous data transmission using human body as transmission medium.

The electrical property between an electrode and skin or tissue is one of the important issues for communication performance of the transcutaneous communication system (TCS) using a human body as a conductive medium.In this study, we used a simple method to measure interface resistance between the electrode and skin on the surface of the body. The electrode-electrode impedance was measured by a commercially available LCR meter with changes in the distance between two electrodes on an arm of a healthy male subject, and we obtained the tissue resistivity and electrode-skin interface resistance using the cross-sectional area of the arm.We also measured transmission gain of the TCS on the surface of the body, and we investigated the relationship between electrode-skin interface resistance and transmission gain. We examined four kinds of electrodes: a stainless steel electrode, a titanium electrode, an Ag-AgCl electrode and an Ag-AgCl paste electrode. The stainless steel electrode, which had lower electrode-skin resistance, had higher transmission gain.The results indicate that an electrode that has lower electrode-skin resistance will contribute to improvement of the performance of the TCS and that electrode-skin interface resistance is one of valuable evaluation parameters for selecting an optimum electrode for the TCS.

Evaluation of titanium mesh electrode using for transcutaneous intrabody communication by tissue-electrode impedance.

We developed a new transcutaneous communication system (TCS) that uses the human body as a conductive medium for monitoring and controlling an artificial heart and other implanted artificial organs in the body. The TCS is able to transmit data between everywhere on the surface of the body and everywhere inside the body, however poor contact between tissue and the electrode influences on communication performance. Thus in this study, we have developed a titanium mesh electrode for the internal transmission electrode. The titanium mesh electrode has advantages of histocompatibility and mechanical stable contact to the tissue by infiltration of the tissue into the titanium mesh like as an extracellular matrix. There titanium mesh electrodes were implanted separately into the dorsal region of the rats under the skin and the electrical performance of the titanium mesh electrode was evaluated by means of measuring the electrode-tissue boundary resistance. In vivo experimental results showed that the titanium mesh electrode had stable mechanical contact to tissue and lower electrode -tissue boundary resistance. In conclusion, the titanium mesh electrode showed excellent histocompatibility it realized stable contact to tissue as anchor, and it had superior electrical property. Thus the titanium mesh electrode is suitable for an internal electrode of the TCS to monitor artificial organs implanted into the body.

Transcutaneous communication system using the human body as conductive medium: influence of transmission data current on the heart.

We developed a new transcutaneous communication system (TCS) that uses the human body as a conductive medium for monitoring and controlling artificial hearts and other artificial organs in the body.In this study, the physiological effect of data current discharged into the body during data transmission was evaluated by an animal experiment using a goat. The external and internal units of the new TCS each mainly consist of a data transmitter and a data receiver. The data transmitter has an amplitude shift keying (ASK) modulator (carrier frequencies: 4 and 10 MHz) and an electrode.The internal unit of the TCS was fixed on the pericardium and the external unit was placed on the left ear, and each transmitter discharged an ASK-modulated current of 7 mA (RMS) into the conscious goat. The TCS was able to transmit data for 4 weeks under full duplex communication with a transmission rate of 115 kbps. On the 28th postoperative day, an electrocardiogram was measured during data transmission. Cardiac rhythm and waveform of the electrocardiogram were not changed before and during bidirectional data transmission. Also, no adverse effect on the heart was observed by autopsy.

Bacteriogenic Fe(III) (oxyhydr)oxides characterized by synchrotron microprobe coupled with spatially resolved phylogenetic analysis.

Ubiquitous presence of microbes in aquatic systems and their inherent ability of biomineralization make them extremely important agents in the geochemical cycling of inorganic elements. However, the detailed mechanisms of environmental biomineralization (e.g., the actual reaction rates, the temporal and spatial dynamics of these processes) are largely unknown, because there are few adequate analytical techniques to observe the biogenic oxidation/reduction reactions in situ. Here, we report a novel technical approach to characterize specific biominerals associated with a target microbe on high spatial resolution. The technique was developed by combining directly in situ phylogenetic analysis, fluorescence in situ hybridization (FISH), with a synchrotron microprobe method, micro X-ray absorption fine structure spectroscopy (µ-XAFS), and was applied to iron mineral deposition by iron(II)-oxidizing bacteria (IOB) in environmental samples. In situ visualization of microbes revealed that in natural iron mats, Betaproteobacteria dominated by IOB were dominantly localized within 10 µm of the surface. Furthermore, in situ chemical speciation by the synchrotron microprobe suggested that the Fe local structure at the IOB accumulating parts was dominantly composed of short-ordered Fe-O(6) linkage, which is not observed in bulk iron mat samples. The present study indicates that coupled XAFS-FISH could be a potential technique to provide direct information on specific biogenic reaction mediated by target microorganism.