Construction and evaluation of a neurofeedback system using finger tapping and near-infrared spectroscopy.

Introduction: Neurofeedback using near-infrared spectroscopy (NIRS) has been used in patients with stroke and other patients, but few studies have included older people or patients with cognitive impairment. Methods: We constructed a NIRS-based neurofeedback system and used finger tapping to investigate whether neurofeedback can be implemented in older adults while finger tapping and whether brain activity improves in older adults and healthy participants. Our simple neurofeedback system was constructed using a portable wearable optical topography (WOT-HS) device. Brain activity was evaluated in 10 older and 31 healthy young individuals by measuring oxygenated hemoglobin concentration during finger tapping and neurofeedback implementation. Results: During neurofeedback, the concentration of oxygenated hemoglobin increased in the prefrontal regions in both the young and older participants. Discussion: The results of this study demonstrate the usefulness of neurofeedback using simple NIRS devices for older adults and its potential to mitigate cognitive decline.

Clinical Impact of Preoperative Prognostic Nutritional Index in Surgical Patients With Pancreatic Cancer Treated With Perioperative Adjuvant Chemotherapy.

BACKGROUND/AIM: The prognostic nutritional index (PNI) is used as a marker to evaluate the nutritional and immunological status of patients with various cancers. This study aimed to investigate whether preoperative PNI is a prognostic factor in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 232 pancreatic cancer patients who underwent surgical resection with perioperative adjuvant chemotherapy between January 2013 and December 2022. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression models. RESULTS: The optimal cutoff value for the preoperative PNI was 44.3 in the present study. PNI <44.3 was associated with older age (p<0.001) and affected the clinical course of postoperative adjuvant chemotherapy. The PNI <44.3 had an important influence on the decreased OS (25.1 vs. 39.0 months) and RFS (13.1 vs. 22.8 months). In univariate and multivariate analyses, the preoperative PNI was an independent prognostic factor for OS [hazard ratio (HR)=1.682, 95% confidence interval (CI)=1.059-2.673, p=0.028] and RFS (HR=1.559, 95% CI=1.037-2.344, p=0.033). CONCLUSION: Preoperative PNI is a prognostic factor for both OS and RFS in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. This study suggests that a low PNI may cause a lack of full-dose adjuvant chemotherapy, leading to recurrence and resulting in a poor prognosis for surgical pancreatic cancer patients treated with perioperative adjuvant chemotherapy.

Non-invasive intraductal oncocytic papillary neoplasm forming a protruding lesion toward the duodenum from the accessory papilla: a case report.

BACKGROUND: Intraductal oncocytic papillary neoplasm (IOPN), previously classified as a subtype of intraductal papillary mucinous neoplasm (IPMN), has been described as an independent disease by the WHO since 2019. IOPN is a rare tumor, with few reported cases. Herein, we report a case of resected non-invasive IOPN that formed a lesion protruding toward the duodenum from the accessory papilla. CASE PRESENTATION: An 80-year-old woman was referred to our hospital because of a giant mass in the pancreatic head detected on abdominal contrast-enhanced computed tomography (CT) performed for a close examination of a mass in the right breast. CT revealed a 90-mm-sized tumor with a mixture of solid and cystic components, with contrast enhancement in the pancreatic head, and a dilated main pancreatic duct. Esophagogastroduodenoscopy revealed a semi-circumferential papillary tumor protruding toward the duodenal lumen, which did not protrude from the papilla of Vater. Transpapillary biopsy led to a preoperative diagnosis of IPMN with an associated invasive carcinoma. As there were no distant metastasis, open subtotal stomach-preserving pancreaticoduodenectomy was performed. Analysis of the surgical specimen and histopathological examination revealed that the tumor was an IOPN that protruded toward the duodenal mucosa from the accessory papilla while replacing the duodenal mucosa with no obvious stromal invasion. CONCLUSION: IOPN is a rare and poorly recognized tumor with few reported cases. There have been no reports describing IOPN forming a protruding lesion toward the duodenum from the accessory papilla. Therefore, further accumulation of cases such as this one is important to advance the study of IOPN.

Clinical Impact of Preoperative Neutrophil-to-Lymphocyte Ratio in Surgical Patients With Pancreatic Cancer.

BACKGROUND/AIM: The prognosis of patients with pancreatic cancer remains poor, despite recent advances in surgical techniques, perioperative care, neoadjuvant and adjuvant chemotherapy. This study aimed to investigate the preoperative neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor and determine the optimal cutoff value in surgical patients with pancreatic cancer. PATIENTS AND METHODS: We retrospectively enrolled 461 patients with pancreatic cancer who underwent resection between January 2013 and December 2022 in the Department of Gastrointestinal Surgery at Kanagawa Cancer Center. The association between continuous or categorical variables and NLR was analyzed using the Mann-Whitney U-test and Fisher's exact test. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazard regression models. RESULTS: The optimal cutoff value for the preoperative NLR was 3.2. The NLR≥3.2 was associated with a large tumor size (p=0.005), poor histological differentiation (p=0.002), and less adjuvant chemotherapy (p=0.048). The NLR≥3.2 had an important influence on the decreased OS (21.6 vs. 25.8 months), and RFS (10.3 vs. 14.3 months). In univariate and multivariate analyses, the preoperative NLR was an independent prognostic factor for OS (p=0.022) and RFS (p=0.002). CONCLUSION: Preoperative NLR (cutoff value: 3.2) within two weeks before surgery is a prognostic factor for OS and RFS in surgical patients with pancreatic cancer. This study could help establish evidence on the immune system's impact and a unified treatment strategy pre-surgery, potentially improving the prognosis for patients with pancreatic cancer.

Risk factors for early recurrence in patients with pancreatic ductal adenocarcinoma who underwent curative resection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and surgical resection is the only potentially curative approach. However, the rate of recurrence remains high, particularly within the first 6 months, and is associated with a poor prognosis. The present study evaluated the clinical characteristics and risk factors for early recurrence in pancreatic ductal adenocarcinoma (PDAC) patients who underwent curative resection, regardless of the use of neoadjuvant chemotherapy, to identify predictive factors associated with early recurrence and poor outcomes as well as to determine the optimal treatment strategy for patients at high risk of early recurrence after surgical resection. METHODS: Patients who underwent pancreatic resection for PDAC at our institution from 2013 to 2021 were included in this study. We investigated the clinicopathological features of patients in groups: those with recurrence within 6 months, recurrence between 6 and 12 months, and recurrence beyond 12 months or no recurrence. A logistic regression analysis identified covariates associated with early recurrence at 6 and 12 months. RESULTS: The study included 403 patients with a median follow-up of 25.7 months. Recurrence was observed in 279 patients, with 14.6% recurring within 6 months, 23.3% within 6-12 months, and 62% after 12 months or not at all. The preoperative CA19-9 level, modified Glasgow prognostic score (mGPS), and positive peritoneal cytology were significant risk factors for early recurrence within 6 months, while positive peritoneal cytology, lymph node metastasis, and the absence of adjuvant chemotherapy were significant risk factors for recurrence within 12 months. For patients who received preoperative chemotherapy or chemoradiotherapy, the preoperative CA19-9 level, mGPS, and positive peritoneal cytology were significant independent risk factors for early recurrence within 6 months, while positive peritoneal cytology, lymph node metastasis, and the absence of adjuvant chemotherapy were significant independent risk factors for recurrence within 12 months. The study concluded that the overall survival after surgical resection for potentially resectable PDAC worsened according to the number of risk factors present in the patient. CONCLUSIONS: We clarified that preoperative CA19-9, positive peritoneal cytology, and the lack of adjuvant chemotherapy were consistent predictors for early recurrence within 6 and 12 months. In addition, an increased number of risk factors affecting the patient was associated with a poorer overall survival after potentially curable resection. Calculating the number of risk factors for early recurrence may be an essential predictive factor when considering treatment strategies.

Comparison of Cerebral Blood Volume during Cold and Warm Stimulation in Elderly and Young Subjects.

Background: Dementia involves a neuronal loss in the primary somatosensory cortex of the parietal lobe, causing dementia patients to perceive pain stimuli hardly. The function of temperature sensation declines. Studies measuring brain blood volume using near-infrared light have reported that patients suffering from dementia have less activation than healthy elderly people. However, the majority of these studies used tests related to cognitive function and the frontal lobe, and few have examined thermal sensation. Objective: The present study aimed to investigate the effect of cold and warm stimulation on cerebral blood volume in elderly and young subjects. Material and Methods: This observational study measured changes in oxygenated hemoglobin concentrations in the frontal cortex during cold and warm stimulation in elderly and young subjects using a near-infrared light device. The mean and standard deviation of the change in oxygenated hemoglobin concentration before and after cold and warm stimulation, as well as the center-of-gravity values, were compared between the young and the elderly. Results: During warm stimulation, the younger subjects showed an increase in blood oxygenated hemoglobin levels; however, the difference was not significant. For the elderly, no change was observed during the task. The center of gravity values was lower in the young compared to the elderly which was similar to the reaction threshold. No significant changes were observed during cold stimulation. Conclusion: Thermal sensation thresholds were impaired in the elderly compared to the young; however, cerebral blood volume changes were unclear.

Carbon Ion Radiotherapy Versus Perioperative Adjuvant Chemotherapy and Curative Surgery for Resectable Pancreatic Cancer.

BACKGROUND/AIM: The standard treatment for resectable pancreatic cancer is preoperative adjuvant chemotherapy (NAC) + curative surgery + adjuvant chemotherapy. Although excellent local control results of carbon ion radiotherapy (CIRT) for pancreatic cancer have been reported, no reports have compared CIRT with the standard treatment for resectable pancreatic cancer. In this study, we compared the results of CIRT for resectable pancreatic cancer with those of standard therapy and investigated the usefulness of CIRT. PATIENTS AND METHODS: The subjects were 35 patients who underwent CIRT for clinical cT1-2, N0-1, and M0 cancers at Kanagawa Cancer Center, Yokohama, Japan, from September 2018 to September 2021, and 110 patients who underwent standard treatment (NAC + curative surgery + adjuvant). Overall survival (OS) and recurrence-free survival (PFS) were compared between the two groups using propensity score-matching (PSM). RESULTS: Twenty-three CIRT monotherapy patients were matched with NAC + curative surgery + adjuvant chemotherapy patients by PSM. Although there was no significant difference in RFS between the two groups, OS was significantly poorer in the CIRT monotherapy group than in the NAC + curative surgery + adjuvant chemotherapy group. CONCLUSION: This single-centre retrospective propensity score-matched comparison of CIRT and NAC + curative resection + adjuvant chemotherapy as the standard therapy for resectable pancreatic cancer showed an inferiority of CIRT in terms of OS, but no difference in PFS. Therefore, CIRT monotherapy may be a treatment strategy for patients with contraindications for standard treatment of curative surgery plus perioperative chemotherapy.

[A Case of Remnant Gastric Necrosis after Laparoscopy-Assisted Distal Gastrectomy].

A 77-year-old man with a medical history of hypertension, dyslipidemia, angina pectoris, and internal carotid artery stenosis underwent laparoscopy-assisted distal gastrectomy, D2 lymphadenectomy, and Billroth Ⅰ reconstruction for advanced gastric cancer. Hematologic examination revealed severe anemia on postoperative day 2, and abdominal CT scan detected contrast media leakage into the remnant gastric lumen. Upper gastrointestinal endoscopy revealed mucosal necrosis and ulceration of a large range. The patient recovered with conservative treatment and was discharged on postoperative day 18. Endoscopic balloon dilation was required to improve anastomotic stenosis after discharge, after which the patient received adjuvant chemotherapy. The stomach is resistant to ischemic changes because of the microvascular networks in the stomach wall; thus, gastric remnant necrosis after gastrectomy is rare. However, for patients with arterial sclerosis, such as in this case, physicians must consider the range of gastrectomy and reconstruction methods.

[A Case of Laparoscopy-Assisted Surgery for Intestinal Malignant Lymphoma with Bowel Obstruction].

An 83-year-old woman visited our emergency department with a chief complaint of abdominal pain and vomiting. Abdominal computed tomography showed thickening of the wall of the small intestine in the right middle abdomen and marked bowel dilation and fluid retention in the oral side of the small intestine. The patient was diagnosed with adhesive bowel obstruction and hospitalized for conservative treatment. However, the treatment was unsuccessful, and laparoscopic surgery was performed. The intraoperative findings included thickening of the wall and hardening of the obstructed part, suggestive of an intestinal tumor; thus, this part was resected. A histopathological examination revealed diffuse infiltration of large-sized atypical lymphocytes in the tumor, and diffuse large B-cell lymphoma was diagnosed through immunochemical staining. The postoperative course was uneventful, and the lymphoma has not recurred. Intestinal malignant lymphoma rarely causes bowel obstruction without invagination. Here, we report this case and review the literature.

[A Case of Port-Site Herniation from an Eight mm Port after Robot-Assisted Distal Gastrectomy].

A 63-year-old-woman was diagnosed with gastric cancer cStage ⅠA after ESD, and then, underwent robot-assisted distal gastrectomy. She vomited on the postoperative day 2 and then was inserted nasogastric tube. The amount of drainage from the tube was increased on the postoperative day 5, therefore, abdominal computed tomography scan was performed, which showed herniation of small bowel at the 8 mm port site in the left upper abdomen. The emergent surgery was performed because of difficulty in manual reduction. Intraoperative findings showed that small intestine was incarcerated at the left 8 mm port-site. The intestine was released by incising the fascia of hernia orifice, then, the fascia was repaired. There was no recurrence of gastric cancer and port-site hernia for 34 months after surgery. In general, the fascia of over 10 mm port site is sutured and closed to avoid port-site hernia, however, it is unclear whether the fascia of 8 mm port-site should be closed after robotic surgery. Since we experienced this case, we have also performed fascia suture on the 8 mm port-site in all cases. And then, we could prevent occurrence of port-site hernia in the 8 mm port-site.

[A Case of Undifferentiated Intestinal Carcinoma].

Undifferentiated cancer of the small intestine has a poor prognosis and has rarely been reported.We report a case of undifferentiated intestinal carcinoma.A 55-year-old man presented with epigastralgia in December 2018. Blood test results showed a high degree of anemia.Contrast -enhanced abdominal CT showed a small intestinal tumor with a diffuse thickened wall along with multiple liver metastases.Capsule endoscopy revealed a bleeding tumor.It was diagnosed as carcinoma by transhepatic-ultrasound-guided core needle biopsy.Given the preoperative diagnosis of intestinal carcinoma, we resected the tumor along with a part of the small intestine and the enlarged lymph nodes.The pathological diagnosis was undifferentiated intestinal carcinoma.The patient was discharged on the 6th postoperative day after surgery.He was scheduled to receive postoperative chemotherapy.There was no evidence of undifferentiated intestinal carcinoma.Herein, we review case reports from the literature.

[A Case of Malignant Peritoneal Mesothelioma Resected Four Times in Five Years].

We report a long-surviving case of malignant peritoneal mesothelioma requiring 4 operations in 5 years. A 63-year-old man was diagnosed with gastrointestinal stromal tumor(GIST)that was excised for the first time in June 2011. The pathological diagnosis was malignant peritoneal mesothelioma. Thereafter, we excised recurrences of the tumor in the hepatic hilum in December 2011. Similar operations were performed in March 2012 and August 2015 because of tumors in the small bowel mesentery and the segment 8 of the liver. The pathological diagnosis was malignant peritoneal mesothelioma. It is an extremely rare variant of malignant peritoneal mesothelioma. There is no record of multiple excision of malignant peritoneal mesothelioma for recurrences. In this case, the cause of long survival was considered to be the excision of recurrent tumors.

[Eight Cases of Primary Carcinoma of the Vermiform Appendix].

Primary carcinoma of the vermiform appendix is a rare neoplasm, and its treatment strategy has not yet been established. We retrospectively analyzed 8 cases of primary carcinoma of the vermiform appendix from 2007 to 2017. Six cases were male and two were female, with a median age of 60.5 years. Ileocecal resection and right hemicolectomy were performed in 7 cases and 1 case, respectively. Regarding pathological staging, 5 cases were of pStage Ⅱ, 2 were of pStage Ⅲa, and 1 was of pStage Ⅳ. Three cases had recurrences after curative resection. The postoperative median overall survival time was 45 months. Three cases with a tumor diameter of 20mm were alive without any recurrence; however, 3 of 5 cases with a tumor diameter of B21mm had recurrences. Although only 1 of 3 cases with adjuvant chemotherapy(pStage Ⅲa case)had recurrence, 2 of 4 cases without adjuvant chemotherapy, including a pStage Ⅱ case, had recurrences. Early diagnosis, surgery, and adjuvant chemotherapy could improve the long-term outcomes of patients with primary carcinoma of the vermiform appendix.

Non-invasive spatial visualization system of exhaled ethanol for real-time analysis of ALDH2 related alcohol metabolism.

A novel imaging system of ethanol in exhaled breath induced by acetaldehyde dehydrogenase (ALDH2)-related alcohol metabolism has been developed. The system provides an image of ethanol distribution as chemiluminescence (CL) on an enzyme-immobilized support. The spatiotemporal change of CL generated by ethanol in exhaled breath after oral administration of ethanol was detected by employing an electron multiplier CCD (EM-CCD) camera, illustrated and analyzed. Prior to measurement of standard gaseous ethanol and ethanol in exhaled breath, the system was optimized by investigating the enzyme-immobilized supports, concentration of substrate and pH condition of Tris-HCl buffer solution. The ethanol skin patch test, a simple method as an indicator of ALDH2, was performed on healthy volunteers. Breath samples of 5 volunteers with ALDH2 (+) and 5 volunteers with ALDH2 (-) were used for exhaled ethanol analysis. Concentration-time profiles of exhaled ethanol obtained from all volunteers were analyzed over a period of 120 min after oral administration of ethanol (0.4 g per kg body weight) in the form of beer which contains 5% of alcohol. The results obtained from the system showed that the peaks of exhaled ethanol concentrations appeared at 30 min, which was considered as a rapid ethanol absorption phase following first-order kinetics. Exhaled ethanol concentrations of volunteers with ALDH2 (+) were lower than volunteers with ALDH2 (-) and the digestion of ethanol in volunteers with ALDH2 (+) was faster than in volunteers with ALDH2 (-). The eliminations were analyzed to follow zero-order kinetics with a rate constant for each group.

Biomedical soft contact-lens sensor for in situ ocular biomonitoring of tear contents.

A soft contact-lens biosensor (SCL-biosensor) for novel non-invasive biomonitoring of tear fluids was fabricated and tested. Wearing a biosensor on eye enabled the in situ monitoring of tear contents. The biosensor has an enzyme immobilized electrode on the surface of a polydimethyl siloxane (PDMS) contact lens. The SCL-biosensor was fabricated using microfabrication techniques for functional polymers (PDMS and 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer). In investigation of in vitro characterization, the SCL-biosensor showed excellent relationship between the output current and glucose concentration from 0.03 to 5.0 mmol·L(-1), with a correlation coefficient of 0.994. The calibration range covered the reported tear glucose concentrations (0.14 mmol·L(-1)). Based on the result, ocular biomonitoring with the SCL-biosensor was carried out. The SCL-biosensor well worked both in the static state and the dynamic state. The tear glucose level of rabbit was estimated to 0.12 mmol·L(-1) at first and then the tear turnover was successfully calculated to be 29.6 ± 8.42% min(-1). The result indicated that SCL-biosensor is useful for advanced biomonitoring on eye.

Fluorescence immunoassay using an optical fiber for determination of Dermatophagoides farinae (Der f1).

Immunoassay methods are generally used for measuring of allergenic substances. However, they need special facilities, skilled handling, and time-consuming procedure. In this work, a fiber-optic immunoassay system which could measure allergen by fluorescent intensities of immune complexes formed by allergens and fluorescently labeled antibodies was established. Immune complexes absorbed on the optical fiber probe surface, and excitation light was injected into the probe, then evanescent field is created in the proximity of the probe. The fluorophores were excited by the evanescent light, and fluorescence was detected by a photo diode. The target allergen detected by our system was Der f1 derived from Dermatophagoides farinae that is one of the house dust mite and major source of inhaled allergens. The fluorophore used labeling on detecting antibody was cyanine 5. The system enabled to detect and quantitatively determine of Der f1. The measurement range was from 0.24 to 250 ng/ml, and the result competes with ELISA. The measurement time was 16 min/sample. The immunoassay system was applied to measurement of Der f1 from actual dust samples. Calculated values of Der f1 showed good correlations between the fiber-optic fluoroimmunoassay and ELISA.

Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment.

A contact lens (CL) biosensor for in situ monitoring of tear glucose was fabricated and tested. Biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and polydimethyl siloxane (PDMS) were employed as the biosensor material. The biosensor consists of a flexible Pt working electrode and a Ag/AgCl reference/counter electrode, which were formed by micro-electro-mechanical systems (MEMS) technique. The electrode at the sensing region was modified with glucose oxidase (GOD). The CL biosensor showed a good relationship between the output current and glucose concentration in a range of 0.03-5.0mM, with a correlation coefficient of 0.999. The calibration range covered the reported tear glucose concentrations in normal and diabetic patients. Also, the CL biosensor was applied to a rabbit for the purpose of tear glucose monitoring. The basal tear glucose was estimated to 0.11 mM. Also, the change of tear glucose induced by the change of blood sugar level was assessed by the oral glucose tolerance test. As a result, tear glucose level increased with a delay of 10 min from blood sugar level. The result showed that the CL biosensor is expected to provide further detailed information about the relationship between dynamics of blood glucose and tear glucose.

Biochemical gas sensor (bio-sniffer) for ultrahigh-sensitive gaseous formaldehyde monitoring.

An ultrahigh-sensitive fiber-optic biochemical gas sensor (bio-sniffer) for continuous monitoring of indoor formaldehyde was constructed and tested. The bio-sniffer measures gaseous formaldehyde as fluorescence of nicotinamide adenine dinucleotide (NADH), which is the product of formaldehyde dehydrogenase (FALDH) reaction. The bio-sniffer device was constructed by attaching a flow cell with a FALDH immobilized membrane onto a fiber-optic NADH measurement system. The NADH measurement system utilizes an ultraviolet-light emitting diode (UV-LED) with peak emission of 335 nm as an excitation light source. The excitation light was introduced to an optical fiber probe, and fluorescence emission of neighboring NADH, which was produced by applying formaldehyde vapor to the FALDH membrane, was concentrically measured with a photomultiplier tube. Assessment of the bio-sniffer was carried out using a standard gas generator. Response, calibration range and selectivity to other chemical substances were investigated. Circulating phosphate buffer, which contained NAD+, available for continuous monitoring of formaldehyde vapor. The calibration range of the bio-sniffer was 2.5 ppb to 10 ppm, which covers the guideline value of the World Health Organization (80 ppb). High selectivity to other gaseous substances due to specific activity of FALDH was also confirmed. Considering its high sensitivity, a possible application of the bio-sniffer is continuous indoor formaldehyde monitoring to provide healthy residential atmosphere.

2D spatiotemporal visualization system of expired gaseous ethanol after oral administration for real-time illustrated analysis of alcohol metabolism.

A novel 2-dimensional spatiotemporal visualization system of expired gaseous ethanol after oral administration for real-time illustrated analysis of alcohol metabolism has been developed, which employed a low level light CCD camera to detect chemiluminescence (CL) generated by catalytic reactions of standard gaseous ethanol and expired gaseous ethanol after oral administration. First, the optimization of the substrates for visualization and the concentration of luminol solution for CL were investigated. The cotton mesh and 5.0 mmol L(-1) luminol solution were selected for further investigations and this system is useful for 0.1-20.0 mmol L(-1) of H(2)O(2) solution. Then, the effect of pH condition of Tris-HCl buffer solution was also evaluated with CL intensity and under the Tris-HCl buffer solution pH 10.1, a wide calibration range of standard gaseous ethanol (30-400 ppm) was obtained. Finally, expired air of 5 healthy volunteers after oral administration was measured at 15, 30, 45, 60, 75, 90, 105 and 120 min after oral administration, and this system showed a good sensitivity on expired gaseous ethanol for alcohol metabolism. The peaks of expired gaseous ethanol concentration appeared within 30 min after oral administration. During the 30 min after oral administration, the time variation profile based on mean values showed the absorption and distribution function, and the values onward showed the elimination function. The absorption and distribution of expired gaseous ethanol in 5 healthy volunteers following first-order absorption process were faster than the elimination process, which proves efficacious of this system for described alcohol metabolism in healthy volunteers. This system is expected to be used as a non-invasive method to detect VOCs as well as several other drugs in expired air for clinical purpose.

An autonomous drug release system based on chemo-mechanical energy conversion "Organic Engine" for feedback control of blood glucose.

A novel autonomous drug release system was fabricated and tested. The system consists of two integrated units: decompression unit and drug release unit. The decompression unit was fabricated by separating a cylindrical cell into a top cell (gas phase) and a bottom cell (liquid phase) by glucose oxidase (GOD) enzyme immobilized membrane. The enzyme membrane recognizes glucose and converts chemical energy found in glucose to mechanical energy. The linear correlation between glucose concentration and de-pressure slope of the top cell was revealed as applying glucose solution to the bottom cell. Afterward, the drug release unit which utilizes the energy of the decompression unit as a power source was fabricated and evaluated by recording its release actions. The drug release unit was made to release at a constant quantity of drug in the liquid phase. The system was then fabricated by combining the decompression unit and the drug release unit. And it was evaluated in an open loop and in a closed loop by applying a mixture of glucose solution (100 mmol/l) and NADH(+) using glucose dehydrogenase enzyme (GDH) as a glucose reducer. Glucose concentration decreased gradually in the closed loop and, as a consequence, interval time of the GDH release became longer. In other words, an inverse correlation between actuation interval of the system and glucose concentration was shown. As a result, the possibility of feedback control of glucose concentration by the drug release system without external energy was confirmed.