Development and validation of the Japanese version of the team job crafting scale for nurses.

Team job crafting, which refers to designing the task, relational, and cognitive aspects of a job, is thought to be beneficial for nurses working in the ward. There are no scales to assess team job crafting among nurses. This study aimed to develop and examine the reliability and validity of a scale to measure team job crafting. Based on literature reviews and interviews, potential items were created. A total of 293 nurses working on 19 wards in two hospitals in Japan were asked to complete a questionnaire twice. A series of exploratory factor analyses (EFAs) were conducted to select the final items. For convergent validity, multilevel correlations were calculated. Cronbach's α and intra-class correlation coefficients (ICCs) were calculated for reliability. A total of 190 participants responded to the baseline survey and 152 responded to the retest. The EFAs yielded a three-factor structure comprising 13 items. The three factors are task crafting considering the team's growth, cognitive crafting for members' respect and reflection of meaningfulness of work, and relational crafting for smooth information sharing. Cronbach's α ranged from .810 to .831, and test-retest ICCs ranged from 0.571 to 0.710. At the individual level, team job crafting had small-to-moderate correlations with individual levels of job crafting, job control, supervisor support, co-worker support, job satisfaction, workplace social capital, and work engagement. The ICC of the team job crafting scores of 0.125 indicated meaningful variation across wards. At the ward-level, nonsignificant but strong correlations were found with workplace social capital, job satisfaction, and psychological distress. This scale showed acceptable levels of reliability and validity. It would be useful in monitoring and improving team job crafting to increase team members' well-being and performance.

Imidazoline 1 receptor activation preserves respiratory drive in spontaneously breathing newborn rats during dexmedetomidine administration.

BACKGROUND: Dexmedetomidine is an alpha-2 (α2 ) adrenoceptor and imidazoline 1 (I1 ) receptor agonist that provides sedation without loss of respiratory drive. AIMS: The aim of this study was to elucidate the involvement of α2 -adrenoceptor and I1 receptor in the cardiorespiratory changes induced by dexmedetomidine in spontaneously breathing newborn rats. METHODS: An abdominal catheter to administer drugs and three subcutaneous electrodes to record electrocardiographic data were inserted into 2- to 5-day-old Wistar rats under isoflurane anesthesia. In individual chambers, each rat was intraperitoneally administered dexmedetomidine (50 µg·kg-1 ) followed 5 min later by normal saline or 1, 5, or 10 mg·kg-1 atipamezole (selective α2 -adrenoceptor antagonist) or efaroxan (α2 -adrenoceptor/I1 receptor antagonist). Cardiorespiratory indices were recorded before and after drug administration. RESULTS: The administration of dexmedetomidine alone resulted in significant changes to most of the cardiorespiratory indices examined. The addition of 5 or 10 mg·kg-1 atipamezole or 1 mg·kg-1 efaroxan completely ameliorated the dexmedetomidine-associated reduction in heart rate (HR). The addition of 1 mg·kg-1 atipamezole or 1 or 5 mg·kg-1 efaroxan completely ameliorated the dexmedetomidine-associated reduction in respiratory frequency. Mean inspiratory flow (VT /TI ; VT is tidal volume and TI is inspiratory time), which is an index of respiratory drive, was not significantly affected by the administration of dexmedetomidine alone (P = 0.273) or dexmedetomidine + atipamezole (P = 0.605, 0.153, 0.138 for 1, 5, 10 mg·kg-1 atipamezole, respectively); however, it was significantly decreased after the administration of dexmedetomidine + efaroxan (P = 0.029, <0.001, <0.001 for 1, 5, 10 mg·kg-1 efaroxan, respectively). CONCLUSIONS: Our results suggest that in newborn rats undergoing dexmedetomidine sedation, the α2 -adrenoceptor, but not I1 receptor, is involved in the regulation of HR and respiratory frequency, and that activation of the I1 receptor plays a major role in the maintenance of respiratory drive.

CLUMSY VEIN, the Arabidopsis DEAH-box Prp16 ortholog, is required for auxin-mediated development.

Pre-messenger RNA (pre-mRNA) splicing is essential in eukaryotic cells. In animals and yeasts, the DEAH-box RNA-dependent ATPase Prp16 mediates conformational change of the spliceosome, thereby facilitating pre-mRNA splicing. In yeasts, Prp16 also plays an important role in splicing fidelity. Conversely, PRP16 orthologs in Chlamydomonas reinhardtii and nematode do not have an important role in general pre-mRNA splicing, but are required for gene silencing and sex determination, respectively. Functions of PRP16 orthologs in higher plants have not been described until now. Here we show that the CLUMSY VEIN (CUV) gene encoding the unique Prp16 ortholog in Arabidopsis thaliana facilitates auxin-mediated development including male-gametophyte transmission, apical-basal patterning of embryonic and gynoecium development, stamen development, phyllotactic flower positioning, and vascular development. cuv-1 mutation differentially affects splicing and expression of genes involved in auxin biosynthesis, polar auxin transport, auxin perception and auxin signaling. The cuv-1 mutation does not have an equal influence on pre-mRNA substrates. We propose that Arabidopsis PRP16/CUV differentially facilitates expression of genes, which include genes involved in auxin biosynthesis, transport, perception and signaling, thereby collectively influencing auxin-mediated development.

Potential Use of Thioalkylated Mannose-Modified Dendrimer (G3)/α-Cyclodextrin Conjugate as an NF-κB siRNA Carrier for the Treatment of Fulminant Hepatitis.

NF-κB and its associated pathways are complicatedly concerned about hepatic homeostasis. Discriminating inhibition of NF-κB signaling has been expected to treat various liver diseases including fulminant hepatitis. To clarify the potential use of thioalkylated mannose-appended dendrimer (generation 3; G3) conjugates with α-cyclodextrin with average degree of substitution of mannose (DSM4) (Man-S-α-CDE (G3, DSM4)) as a novel antigen presenting cell (APC)-specific siRNA carrier, we evaluated the RNAi effect of NF-κB p65 siRNA (sip65) complex with Man-S-α-CDE (G3, DSM4) both in vitro and in vivo. Man-S-α-CDE (G3, DSM4)/sip65 complex significantly suppressed NF-κB p65 mRNA expression and nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated NR8383 cells, a rat alveolar macrophage cell line, by adequate physicochemical properties and mannose receptor-mediated cellular uptake. Intravenous injection of Man-S-α-CDE (G3, DSM4)/sip65 complex extended the survival rate of LPS-induced fulminant hepatitis model mice. In addition, intravenous administration of Man-S-α-CDE (G3, DSM4)/sip65 complex had the potential to induce the in vivo RNAi effect by significant suppression of mRNA expression of NF-κB p65 and inflammatory cytokines in the liver of fulminant hepatitis model mice induced by LPS/d-galactosamine (d-Gal) without any significant side effects. Also, the serum levels of enzymes were significantly attenuated by injection of Man-S-α-CDE (G3, DSM4)/sip65 complex in fulminant hepatitis model mice. Collectively, these results suggest that Man-S-α-CDE (G3, DSM4) has the potential as a novel APC-selective sip65 carrier for the treatment of LPS/d-Gal-induced fulminant hepatitis in mice.

Temperature-variable apparatus for measuring Barnett field.

We have developed experimental equipment for observing the Barnett effect, in which mechanical rotation magnetizes an object, at low temperatures. A sample in a rotor is rotated bidirectionally using a temperature-controlled high-pressure gas. The stray field generated from the sample due to the Barnett effect was detected using a fluxgate magnetic sensor with a sensitivity on the order of several picoteslas, even at low temperatures. By replacing the rotor with a solenoid coil, the magnetic susceptibility of the sample was estimated from the stray field to be of the same order of magnitude as that due to the Barnett effect. The Barnett field was estimated using the dipole model. To assess the performance of the setup at low temperatures, measurements were performed on commercial magnetite (Fe3O4) nanogranules. We confirmed the accordance of the g' factor between the experimental results using the present setup and those of our previous study performed at room temperature.

Inverse agonism of lysophospholipids with cationic head groups at Gi-coupled receptor GPR82.

GPR82 is an orphan G protein-coupled receptor (GPCR) that has been implicated in lipid storage in mouse adipocytes. However, the intracellular signaling as well as the specific ligands of GPR82 remain unknown. GPR82 is closely related to GPR34, a GPCR for the bioactive lipid molecule lysophosphatidylserine. In this study, we screened a lipid library using GPR82-transfected cells to search for ligands that act on GPR82. By measuring cyclic adenosine monophosphate levels, we found that GPR82 is an apparently constitutively active GPCR that leads to Gi protein activation. In addition, edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine), an artificial lysophospholipid with a cationic head group that exerts antitumor activity, inhibited the Gi protein activation by GPR82. Two endogenous lysophospholipids with cationic head groups, lysophosphatidylcholine (1-oleoyl-sn-glycero-3-phosphocholine) and lysophosphatidylethanolamine (1-oleoyl-sn-glycero-3-phosphoethanolamine), also exhibited GPR82 inhibitory activity, albeit weaker than edelfosine. Förster resonance energy transfer imaging analysis consistently demonstrated that Gi protein-coupled GPR82 has an apparent constitutive activity that is edelfosine-sensitive. Consistent data were obtained from GPR82-mediated binding analysis of guanosine-5'-O-(3-thiotriphosphate) to cell membranes. Furthermore, in GPR82-transfected cells, edelfosine inhibited insulin-induced extracellular signal-regulated kinase activation, like compounds that function as inverse agonists at other GPCRs. Therefore, edelfosine is likely to act as an inverse agonist of GPR82. Finally, GPR82 expression inhibited adipocyte lipolysis, which was abrogated by edelfosine. Our findings suggested that the cationic lysophospholipids edelfosine, lysophosphatidylcholine and lysophosphatidylethanolamine are novel inverse agonists for Gi-coupled GPR82, which is apparently constitutively active, and has the potential to exert lipolytic effects through GPR82.

Possible Use of Non-purine Selective Xanthine Oxidoreductase Inhibitors for Prevention of Exercise-induced Acute Kidney Injury Associated with Renal Hypouricemia.

Exercise-induced acute kidney injury (EIAKI) is frequently complicated with renal hypouricemia (RHUC). In patients with RHUC, limiting anaerobic exercise can prevent EIAKI. However, it is challenging to reduce exercise intensity in athletes. We herein report a 16-year-old Japanese football player with familial RHUC with compound heterozygous mutations in urate transporter 1 (URAT1) who presented with recurrent EIAKI. As prophylaxis (hydration during exercise) could not prevent EIAKI, febuxostat was initiated. EIAKI was not observed for 16 months despite exercising intensively. Hence, non-purine-selective xanthine oxidoreductase inhibitors may decrease the incidence of EIAKI in athletes with RHUC.

Hypoxanthine Reduces Radiation Damage in Vascular Endothelial Cells and Mouse Skin by Enhancing ATP Production via the Salvage Pathway.

An effective method that can protect radiation-damaged tissues from apoptosis and promote tissue repair has not been reported to date. Hypoxanthine (Hx) is an intermediate metabolite in the purine degradation system that serves as a substrate for ATP synthesis via the salvage pathway. In this study, we focused on the transient decrease in intracellular ATP concentration after radiation exposure and examined the protective effect of Hx against radiation-induced tissue damage. Human umbilical vein endothelial cells were X irradiated, and the cell viability and incidence of apoptosis and DNA double-strand breaks (DSBs) were evaluated at different Hx concentrations. We found that in the presence of 2-100 µM Hx, the percentages of DSBs and apoptotic cells after 2, 6 and 10 Gy dose of radiation significantly decreased, whereas cell viability increased in a concentration-dependent manner. Moreover, the addition of Hx increased the levels of AMP, ADP, and ATP in the cells at 2 h postirradiation, suggesting that Hx was used for adenine nucleotide synthesis through the salvage pathway. Administration of a xanthine oxidoreductase inhibitor to a mouse model of radiation dermatitis resulted in increased blood Hx levels that inhibited severe dermatitis and accelerated recovery. In conclusion, the findings provide evidence that increasing the levels of Hx to replenish ATP could be an effective strategy to reduce radiation-induced tissue damage and elucidating the detailed mechanisms underlying the protective effects of Hx could help develop new protective strategies against radiation.

Lymphatic Absorption of Microbial Plasmalogens in Rats.

Plasmalogens, functional glycerophospholipids with biological roles in the human body, are associated with various diseases. Although a variety of saturated and/or unsaturated fatty acids in plasmalogens are presumed to have different functions in the human body, there are limited reports validating such functions of plasmalogens. In this study, we focused on the bacterial plasmalogen derived from Selenomonas ruminantium subsp. lactilytica (NBRC No. 103574) with different main species of hydrocarbon chains at the sn-1 position and shorter fatty acids at the sn-2 position than animal plasmalogens. Optimum culture conditions of S. ruminantium for high-yield production of plasmalogens, such as pH and the concentration of caproic acid, were investigated under anaerobic conditions using a 2-L scale jar fermenter. The obtained plasmalogen mainly consisted of the ethanolamine plasmalogen (PlsEtn). The molar ratios of PlsEtn species obtained from S. ruminantium, at sn-1/sn-2 positions, were p16:1/14:0 (68.4%), p16:1/16:1 (29.2%), p16:1/16:0 (0.7%), p16:1/15:0 (0.3%), and p17:1/14:0 (0.3%). Subsequently, duodenal infusion of the emulsion carrying the lipid extracted from S. ruminantium was carried out in lymph duct-cannulated rats. In the lymphatic plasmalogen of rats, the level of PlsEtns with molar ratios p16:1/14:0 and p16:1/16:1, the main species of plasmalogens from S. ruminantium, increased gradually until 3-4 h after lipid injection and then gradually decreased. In addition, the level of PlsEtns with p16:1/20:4 and p16:1/22:6 rapidly increased, peaking at 1-1.5 h and 1.5-2 h after lipid injection, respectively. The increase in the number of PlsEtns with p16:1/20:4 and p16:1/22:6 suggested that 20:4 and 22:6, the main fatty acids at the sn-2 position in the rat lymphatic plasmalogen, were preferentially re-esterified at the sn-2 position, regardless of the types of hydrocarbon chains at the sn-1 position. Thus, we showed that bacterial PlsEtns with "unnatural" structures against rats could be absorbed into the lymph. Our findings provide insights into the association between the chemical structure of plasmalogens and their biological functions in humans.

Analysis of Purine Metabolism to Elucidate the Pathogenesis of Acute Kidney Injury in Renal Hypouricemia.

Renal hypouricemia is a disease caused by the dysfunction of renal urate transporters. This disease is known to cause exercise-induced acute kidney injury, but its mechanism has not yet been established. To analyze the mechanism by which hypouricemia causes renal failure, we conducted a semi-ischemic forearm exercise stress test to mimic exercise conditions in five healthy subjects, six patients with renal hypouricemia, and one patient with xanthinuria and analyzed the changes in purine metabolites. The results showed that the subjects with renal hypouricemia had significantly lower blood hypoxanthine levels and increased urinary hypoxanthine excretion after exercise than healthy subjects. Oxidative stress markers did not differ between healthy subjects and hypouricemic subjects before and after exercise, and no effect of uric acid as a radical scavenger was observed. As hypoxanthine is a precursor for adenosine triphosphate (ATP) production via the salvage pathway, loss of hypoxanthine after exercise in patients with renal hypouricemia may cause ATP loss in the renal tubules and consequent tissue damage.

Association between cognitive frailty and higher-level competence among community-dwelling older adults.

OBJECTIVES: The purpose of this cross-sectional study was to examine the association between cognitive frailty (CF) and higher-level competence among community-dwelling older adults. METHODS: Data from 871 older adults (aged ≥ 65 years, mean age 74.3 years, 61.5% women) who had participated in a community-based health check survey (Tarumizu Study 2018-2019) were analyzed. CF was defined as comorbid physical frailty and mild cognitive impairment (MCI). We defined physical frailty as either slow walking speed or poor grip strength. MCI was defined as values below the age- and education-adjusted reference threshold in several tests. Participants were categorized into four groups: robust, physical frailty, MCI, and CF. Higher-level competence was assessed using the Japan Science and Technology Agency Index of Competence (JST-IC). The JST-IC consists of 16 items and four subscales (technology usage, information practice, life management and social engagement). The bottom 20-30% score of the JST-IC and each subscale corresponded to poor higher-level competence. RESULTS: The prevalence of CF was 14.4%. Multivariate logistic regression analysis showed that, CF was significantly associated with poor higher-level competence (odds ratio 1.92, 95% confidence interval 1.18-3.13) after adjusting for covariates. Using a similar analysis to assess the JST-IC subscales, CF was associated with limitations on technology usage (odds ratio 2.29, 95% confidence interval 1.36-3.85) and low social engagement (odds ratio 1.62, 95% confidence interval 1.00-2.61). CONCLUSIONS: This study suggests that CF is associated with poor higher-level competence, especially limitations on technology usage and low social engagement.

Association of self-rated health with type and frequency of social interaction during the declaration of COVID-19 state of emergency among Japanese community-dwelling oldest-old adults.

AIM: To investigate whether the type and frequency of social interaction during the state of emergency due to coronavirus disease were associated with self-rated health (SRH) after the state of emergency. METHODS: Data from a cross-sectional study were collected for 889 oldest-old adults in Bibai City, Hokkaido, Japan. In total, 612 participants (mean age: 83.0 ± 4.3 years; women: 51.8%) were included in the analysis, taking biological sex into account. The self-reported questionnaire included questions about demographic variables, SRH (July 2020, after the emergency), and the type and frequency of social interaction (March 2020, during the state of emergency). RESULTS: There was no significant association between social interaction and SRH in men (P > 0.05). Women who had social interactions (both face-to-face and non-face-to-face) more than once a week during the state of emergency reported higher SRH after the emergency than those who did not (odds ratio 2.17, 95% confidence interval 1.07-4.41). CONCLUSIONS: Having both types of interaction more than once a week during the state of emergency was related to higher SRH after the emergency among oldest-old women. It is suggested that having opportunities for both types of interaction at least once a week would potentially be beneficial for high SRH in women, even in situations where the declaration of a state of emergency restricts face-to-face interaction. Geriatr Gerontol Int 2022; 22: 405-411.

Associations Between Personal Values and Work Engagement: A Cross-Sectional Study Using A Representative Community Sample.

OBJECTIVE: This study aimed to investigate associations between personal values and work engagement among workers. METHODS: This cross-sectional study used data from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE) in 2010 and 2017. Personal values were measured by 11 value priorities and by commitment to these values. Multivariate linear regression analyses were conducted to determine the associations between personal values and work engagement. RESULTS: A total of 1946 workers were analyzed. Four personal values (eg, "Improving society") and commitment to values were significantly positively associated with work engagement, while "Graduating from a famous school" was significantly negatively associated. CONCLUSIONS: Some personal values relate to openness to change, self-transcendence, and self-enhancement, and commitment to values showed associations with work engagement. It could be beneficial to consider personal values to enhance work engagement.

Mediating Effects of Work Eudemonic Well-being for the Association Between Psychosocial Work Environment and Overall Eudemonic Well-being Among Japanese Workers: A Cross-sectional Study.

OBJECTIVE: This study aimed to investigate the mediating effects of eudemonic well-being (EWB) at work for the associations between psychosocial work environment and overall EWB among Japanese workers. METHODS: We conducted a cross-sectional study using data from a 2018 survey. psychosocial work environment measures included: job demands, job control, and supervisor and coworker support. Path analysis using structural equation modeling and mediation analysis were applied to examine the mediating effects of work EWB. RESULTS: A total of 834 workers were analyzed. Work EWB completely mediated the associations of job control (ß = 0.288, P < 0.001) and coworker support with overall EWB (ß = 0.178, P < 0.001). CONCLUSIONS: The effects of job control and coworker support associated with overall EWB were fully mediated by work EWB.

Effectiveness of an Internet-Based Machine-Guided Stress Management Program Based on Cognitive Behavioral Therapy for Improving Depression Among Workers: Protocol for a Randomized Controlled Trial.

BACKGROUND: The effect of an unguided internet-based cognitive behavioral therapy (iCBT) stress management program on depression may be enhanced by applying artificial intelligence (AI) technologies to guide participants adopting the program. OBJECTIVE: The aim of this study is to describe a research protocol to investigate the effect of a newly developed iCBT stress management program adopting AI technologies on improving depression among healthy workers during the COVID-19 pandemic. METHODS: This study is a two-arm, parallel, randomized controlled trial. Participants (N=1400) will be recruited, and those who meet the inclusion criteria will be randomly allocated to the intervention or control (treatment as usual) group. A 6-week, six-module, internet-based stress management program, SMART-CBT, has been developed that includes machine-guided exercises to help participants acquire CBT skills, and it applies machine learning and deep learning technologies. The intervention group will participate in the program for 10 weeks. The primary outcome, depression, will be measured using the Beck Depression Inventory II at baseline and 3- and 6-month follow-ups. A mixed model repeated measures analysis will be used to test the intervention effect (group × time interactions) in the total sample (universal prevention) on an intention-to-treat basis. RESULTS: The study was at the stage of recruitment of participants at the time of submission. The data analysis related to the primary outcome will start in January 2022, and the results might be published in 2022 or 2023. CONCLUSIONS: This is the first study to investigate the effectiveness of a fully automated machine-guided iCBT program for improving subthreshold depression among workers using a randomized controlled trial design. The study will explore the potential of a machine-guided stress management program that can be disseminated online to a large number of workers with minimal cost in the post-COVID-19 era. TRIAL REGISTRATION: UMIN Clinical Trials Registry（UMIN-CTR) UMIN000043897; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050125. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30305.

Associations of alpha-actinin-3 genotype with thigh muscle volume and physical performance in older adults with sarcopenia or pre-sarcopenia.

BACKGROUND: This cross-sectional study aimed to investigate the relationship of the ACTN3 genotype with thigh muscle volume and physical performance in older adults with sarcopenia or pre-sarcopenia. METHODS: Data from 64 older Japanese adults (mean age 74.4 ± 6.9 years, women 71.9%) with sarcopenia or pre-sarcopenia were analyzed. Sarcopenia and pre-sarcopenia were defined using the Asian Working Group for Sarcopenia. We collected oral mucosa samples to determine the ACTN3 genotype. Thigh muscle volumes were measured using magnetic resonance imaging. Physical performance was assessed using the usual and maximum gait speed, timed up and go test, and five-repetition sit-to-stand test. Muscle strength was assessed using grip strength. RESULT: The ACTN3 genotype proportions were 20.3% for RR, 51.6% for RX, and 28.1% for XX. Participants with the RR genotype showed greater thigh muscle volume/ht2 compared to those with the RX and XX ACTN3 genotypes (p < 0.05). The multiple linear regression analysis revealed that RX (p < 0.01) and XX (p < 0.01) ACTN3 genotypes, compared to RR, were associated with lower thigh muscle volume/ht2 and with age, sex (reference; men), weight and maximum walking speed. There was no significant difference between physical performance and muscle strength between the ACTN3 genotypes. CONCLUSION: The ACTN3 genotype of the X allele was associated with decreased thigh muscle volume compared to the ACTN3 genotype of RR in older adults with sarcopenia or pre-sarcopenia.

Evaluation of Porcine Intestinal Epitheliocytes as an In vitro Immunoassay System for the Selection of Probiotic Bifidobacteria to Alleviate Inflammatory Bowel Disease.

The use of in vitro systems that allow efficient selection of probiotic candidates with immunomodulatory properties could significantly minimize the use of experimental animals. In this work, we generated an in vitro immunoassay system based on porcine intestinal epithelial (PIE) cells and dextran sodium sulfate (DSS) administration that could be useful for the selection and characterization of potential probiotic strains to be used in inflammatory bowel disease (IBD) patients. Our strategy was based on two fundamental pillars: on the one hand, the capacity of PIE cells to create a monolayer by attaching to neighboring cells and efficiently mount inflammatory responses and, on the other hand, the use of two probiotic bifidobacteria strains that have been characterized in terms of their immunomodulatory capacities, particularly in mouse IBD models and patients. Our results demonstrated that DSS administration can alter the epithelial barrier created in vitro by PIE cells and induce a potent inflammatory response, characterized by increases in the expression levels of several inflammatory factors including TNF-α, IL-1α, CCL4, CCL8, CCL11, CXCL5, CXCL9, CXCL10, SELL, SELE, EPCAM, VCAM, NCF2, and SAA2. In addition, we demonstrated that Bifidobacterium breve M-16V and B. longum BB536 are able to regulate the C-jun N-terminal kinase (JNK) intracellular signalling pathway, reducing the DSS-induced alterations of the in vitro epithelial barrier and differentially regulating the inflammatory response in a strain-dependent fashion. The good correlation between our in vitro findings in PIE cells and previous studies in animal models and IBD patients shows the potential value of our system to select new probiotic candidates in an efficient way.

[Results of chemotherapy in head and neck cancer patients with residual or recurrent tumors after initial treatment].

A study of S-1 chemotherapy treatment of patients with head and neck cancer was conducted in 26 patients with residual or recurrent tumors after the initial treatment, i. e., chemoradiotherapy, radiotherapy and operation. The treatment courses consisted of oral administration of S-1 at a dose of 80 to 120 mg/day depending on the body surface area, for 14 consecutive days followed by a 7-day rest period. The response rate in all patients was 34.6%(9/26). In patients with recurrent tumors, the response rate was 11.1% (1/9). Patients with residual tumors after the initial treatment had a response rate of 47.0% (8/17). The median survival time was 490 days. Moreover, we studied the maintenance of QOL (quality of life) in 15 cases whose deaths were caused by their tumors. The maintenance duration of QOL was 162 to 1,742 days (median 330 days). The mean QOL maintenance rate, i. e., the average period of extended life with stable disease compared to the period from the eternity time of S -1 treatment until patient death, was 81.1% (36.4-98.7%). S-1 is a safe anticancer drug with fewer side-effects than other chemotherapies. S-1 did not cause any serious adverse events in the patients enrolled in this study. Therefore, S-1 appears to be useful for the treatment of patients with head and neck cancer, and it is particularly useful for improving the QOL of patients.

Efficient Anticancer Drug Delivery for Pancreatic Cancer Treatment Utilizing Supramolecular Polyethylene-Glycosylated Bromelain.

Pancreatic cancer is one of the most difficult cancers to treat largely because of the inability of anticancer drugs to penetrate into the cancer tissue as the result of the dense extracellular matrix (ECM). On the other hand, bromelain is known to degrade the ECM in cancerous tissue. However, the half-life of bromelain in blood is short, leading to its low accumulation in tissues. Recently, we developed a reversible poly(ethylene glycol) (PEG) modification technology that is able to improve blood retention of proteins without loss of activity and termed it "Self-assembly PEGylation Retaining Activity (SPRA)" technology. Here, we prepared reversible PEGylated bromelain using SPRA technology (SPRA-bromelain) possessing high activity, long blood retention, and high tumor accumulation and evaluated its potential as a drug delivery system for pancreatic cancer. SPRA-bromelain was prepared by mixing adamantane-modified bromelain and multisubstituted-PEGylated ß-cyclodextrins (ß-CyDs) containing 2 or 20 kDa PEG chains in water. SPRA-bromelain was formed by a host-guest interaction between adamantane and ß-CyD (Kc > 104 M-1). SPRA-bromelain showed high in vitro gelatin-degrading activity and enhanced not only the accumulation of fluorescein isothiocyanate (FITC)-dextran (2 MDa) in the tumor but also the in vivo antitumor activities of doxorubicin and doxorubicin encapsulated in PEGylated liposomes (DOXIL) after intravenous administration in tumor-bearing mice. These findings suggest that SPRA-bromelain could be a powerful tool for drug delivery in pancreatic cancer.