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Purpose: We compared the results of prospective and retrospective cohort studies in the field of digestive surgery to clarify whether the results of prospective cohort studies were more similar to those of randomized controlled trials (RCTs)., Methods: We conducted a secondary analysis of the results to compare the results of RCTs with those of cohort studies in meta-analyses of 18 digestive surgical topics. The data from the prospective and retrospective cohort studies were combined. The summary estimates of each design were compared with those of RCTs. We used the Z score to investigate discrepancies., Results: Twenty-nine outcomes of 11 topics were investigated in 289 cohort studies (prospective, n = 69; retrospective, n = 220). These were compared with the outcomes of 123 RCTs. In comparison to retrospective studies, the summary estimates of the prospective cohort studies were more similar to those of the RCTs [19/29 (prospective) vs. 10/29 (retrospective), P = 0.035). Five of the 29 outcomes of prospective studies and 6 of 29 outcomes of retrospective studies (P = 0.99) showed significant discrepancies in comparison to RCTs., Conclusions: In the digestive surgical field, the results of prospective cohort studies tended to be more similar to those of RCTs than retrospective studies; however, there were no significant discrepancies between the two types of cohort study.

Background: Hypothesis generation is an essential task for clinical research, and it can require years of research experience to formulate a meaningful hypothesis. Recent studies have endeavored to apply crowdsourcing to generate novel hypotheses for research. In this study, we apply crowdsourcing to explore previously unknown allergy-associated factors., Objective: In this study, we aimed to collect and test hypotheses of unknown allergy-associated factors using a crowdsourcing service., Methods: Using a series of questionnaires, we asked crowdsourcing participants to provide hypotheses on associated factors for seven different allergies, and validated the candidate hypotheses with odds ratios calculated for each associated factor. We repeated this abductive validation process to identify a set of reliable hypotheses., Results: We obtained two primary findings: (1) crowdsourcing showed that 8 of the 13 known hypothesized allergy risks were statically significant; and (2) among the total of 157 hypotheses generated by the crowdsourcing service, 75 hypotheses were statistically significant allergy-associated factors, comprising the 8 known risks and 53 previously unknown allergy-associated factors. These findings suggest that there are still many topics to be examined in future allergy studies., Conclusions: Crowdsourcing generated new hypotheses on allergy-associated factors. In the near future, clinical trials should be conducted to validate the hypotheses generated in this study., (©Eiji Aramaki, Shuko Shikata, Satsuki Ayaya, Shin-Ichiro Kumagaya. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 16.05.2017.)

Little is known about the relationship between mild cognitive impairment (MCI) and changes to language abilities. Here, we used the revised Hasegawa Dementia Scale (HDS-R) to identify suspected MCI in elderly individuals. We then analyzed written and spoken narratives to compare the language abilities between study participants with and without MCI in order to explore the relationship between cognitive and language abilities, and to identify a possible indicator for the early detection of MCI and dementia. We recruited 22 people aged 74 to 86 years (mean: 78.32 years; standard deviation: 3.36). The participants were requested to write and talk about one of the happiest events in their lives. Based on HDS-R scores, we divided the participants into 2 groups: the MCI Group comprised 8 participants with a score of 26 or lower, while the Healthy Group comprised 14 participants with a score of 27 or higher. The transcriptions of both written and spoken samples for each participant were used in the measurement of NLP-based language ability scores. Our analysis showed no significant differences in writing abilities between the 2 groups in any of the language ability scores. However, analysis of the spoken narrative showed that the MCI Group had a significantly larger vocabulary size. In addition, analysis of a metric that signified the gap in content between the spoken and written narratives also revealed a larger vocabulary size in the MCI Group. Individuals with early-stage MCI may be engaging in behavior to conceal their deteriorating cognition, thereby leading to a temporary increase in their active spoken vocabulary. These results indicate the possible detection of early stages of reduced cognition before dementia onset through the analysis of spoken narratives.

Background: In surgical trials, complex variables such as equipment development and surgeons' learning curve are involved. The evidence obtained in these trials can thus fluctuate over time. We explored the stability of the evidence obtained during surgery by conducting a cumulative meta-analysis of randomized controlled trials for open and laparoscopic appendectomy., Methods: We conducted a cumulative meta-analysis of randomized controlled trials comparing laparoscopic appendectomy with open appendectomy for acute appendicitis, a topic with the greatest number of trials in the gastroenterological surgical field. We searched the MEDLINE (PubMed), EMBASE, and CINAHL databases up to September 2014 and reviewed the bibliographies. Outcomes were the incidence of intra-abdominal abscess, incidence of wound infection, operative time, and length of hospital stay. We used the 95 % confidence interval (95 % CI) of effect size for the significance test., Results: Sixty-four trials were included in this analysis. Of the 51 trials addressing intra-abdominal abscesses, our cumulative meta-analysis of trials published up to and including 2001 demonstrated statistical significance in favor of open appendectomy (cumulative odds ratio [OR] 2.35, 95 % CI 1.30-4.25). The effect size in favor of open procedures began to disappear after 2001, leading to an insignificant result with an overall cumulative OR of 1.32 (95 % CI 0.84-2.10) when laparoscopic appendectomy was compared with open appendectomy., Conclusions: The evidence regarding treatment effectiveness changed over time, after treatment effectiveness became significant in trials comparing laparoscopic and open appendectomy. Observing only the 95 % confidence interval of effect size from a meta-analysis may not provide conclusive results.

Respiratory quinolones (RQs) are broad-spectrum antimicrobial agents used for the treatment of a wide variety of community-acquired and nosocomial infections. However, bacterial resistance to quinolones has been on the increase. In this study, we investigated the predicted efficacy of RQs for various strains of 9 bacterial species clinically isolated at our university hospital using the Monte Carlo simulation (MCS) method based on pharmacokinetics/pharmacodynamics modeling. In addition, the influence of the patients' renal function on the efficacy of RQs was evaluated. We surveyed antimicrobial susceptibility testing of 9 bacterial species (n = number of strains) [Streptococcus pneumoniae (n = 15), Streptococcus pyogenes (n = 14), Streptococcus agalactiae (n = 19), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24), Escherichia coli (n = 35), Haemophilus influenzae (n = 17), Klebsiella pneumoniae (n = 14), Pseudomonas aeruginosa (n = 31), and Moraxella catarrhalis (n = 11)] to 4 RQs [garenoxacin (GRNX), levofloxacin (LVFX), sitafloxacin (STFX), and moxifloxacin (MFLX)]. We found that compared with the other RQs, Gram-positive cocci was most resistant to LVFX, and that the minimum inhibitory concentration (MIC₉₀) values for S. pneumoniae, S. pyogenes, S. agalactiae, and MSSA were high (2, 16, > 16, and 8 µg/mL, respectively). In regard to Gram-negative rods, the susceptibility of E. coli to RQs was found to be decreased, with the MIC₉₀ values of GRNX, LVFX, STFX, and MFLX being > 16, 16, 1, and 16 µg/mL, respectively. MCS revealed that the target attainment rate of the area under the unbound concentration-time curve divided by the MIC₉₀ (ƒ · AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The ƒ · AUC/MIC target attainment rate of LVFX against S. pneumoniae, S. pyogenes, and S. agalactiae tended to decrease due to increased creatinine clearance, and that of LVFX and STFX against MSSA also tended to decrease. The findings of this study suggest that the drug susceptibility distribution of each RQ varies, even within the same bacterial species, and that the expected efficacy also varies between the drugs. Moreover, the influence of the patient's renal function on the efficacy differed among the 3 renal excretory drugs (GRNX, LVFX, and STFX), thus suggesting that the efficacy also differs. In conclusion, the findings of this study show that for the administration of RQs, it is desirable to select agents in consideration of surveyed sensitivity within the population and the pharmacokinetic characteristics.

A self-standing single-crystal chemical vapor deposited diamond was obtained using lift-off method. It was fabricated into a radiation detector and response function measurements for 14 MeV neutrons were taken at the fusion neutronics source. 1.5% of high energy resolution was obtained by using the (12)C(n, α)(9)Be reaction at an angle of 100° with the deuteron beam line. The intrinsic energy resolution, excluding energy spreading caused by neutron scattering, slowing in the target and circuit noises was 0.79%, which was also the best resolution of the diamond detector ever reported.

Bioenergetic metabolism varies during cell differentiation, but details of B cell metabolism remain unclear. Here, we show the metabolic changes during B cell differentiation in the intestine, where B cells differentiate into IgA(+) plasma cells (PCs). Naive B cells in the Peyer's patches (PPs) and IgA(+) PCs in the intestinal lamina propria (iLP) both used the tricarboxylic acid (TCA) cycle, but only IgA(+) PCs underwent glycolysis. These metabolic differences reflected their dependencies on vitamin B1, an essential cofactor for the TCA cycle. Indeed, the diminished activity of the TCA cycle after dietary vitamin B1 depletion decreased the number of naive B cells in PPs without affecting IgA(+) PCs in the iLP. The maintenance of naive B cells by dietary vitamin B1 was required to induce-but not maintain-intestinal IgA responses against oral antigens. These findings reveal the diet-mediated maintenance of B cell immunometabolism in organized and diffuse intestinal tissues., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

ω3 polyunsaturated fatty acids (PUFAs) have anti-allergic and anti-inflammatory properties, but the immune-metabolic progression from dietary oil remains to be investigated. Here we identified 17,18-epoxyeicostetraenoic acid (17,18-EpETE) as an anti-allergic metabolite generated in the gut from dietary ω3 α-linolenic acid (ALA). Biochemical and imaging mass spectrometry analyses revealed increased ALA and its metabolites, especially eicosapentaenoic acid (EPA), in the intestines of mice receiving ALA-rich linseed oil (Lin-mice). In murine food allergy model, the decreased incidence of allergic diarrhea in Lin-mice was due to impairment of mast cell degranulation without affecting allergen-specific serum IgE. Liquid chromatography-tandem mass spectrometry-based mediator lipidomics identified 17,18-EpETE as a major ω3 EPA-derived metabolite generated from dietary ALA in the gut, and 17,18-EpETE exhibits anti-allergic function when administered in vivo. These findings suggest that metabolizing dietary ω3 PUFAs generates 17,18-EpETE, which is an endogenous anti-allergic metabolite and potentially is a therapeutic target to control intestinal allergies.

Background: Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines., Methods: A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines., Results: Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles., Conclusions: The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The effectiveness of prophylactic antibiotics use for acute necrotizing pancreatitis has been explored and a number of systematic reviews have been published with conflicting results. The timing of antibiotics administration can be fundamental to their effectiveness, but thus far no reviews have focused on the timing of administration., Methods: A systematic review of randomized controlled trials (RCTs) of prophylactic antibiotics for acute necrotizing pancreatitis was conducted using MEDLINE (PubMed), CINAHL and Japana Centra Revuo Medicina. Trials in which antibiotics were administered within 72 h after onset of symptoms or 48 h after admission were included. Our primary outcomes were the mortality rate and the incidence of infected pancreatic necrosis, and secondary outcomes were the incidence of non-pancreatic infection and the incidence of surgical intervention., Results: The search revealed six RCTs with a total of 397 patients. The mortality rates were significantly different for those taking antibiotics (7.4%), and controls (14.4%) (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25-0.94). Also, early prophylactic antibiotics use was associated with reduced incidence of infected pancreatic necrosis (antibiotics 16.3%, controls 25.1%; OR, 0.55; 95% CI, 0.33-0.92)., Conclusion: Early use of prophylactic antibiotics for acute necrotizing pancreatitis is associated with reduced mortality and lower incidence of infected pancreatic necrosis., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

This study's aim was to build a web service that automatically collects and tests hypotheses for possible allergy risks. We crowdsourced for unknown allergy risks, and obtained odds ratios. By using the collected hypotheses, we built a web service that estimates allergy risks from a questionnaire (consisting of 10 questions that we gathered from the crowdsourcing task), and at the end, we asked the users their new hypotheses on possible allergy risks. The web service also asked the users to send their original hypotheses to contribute to find the cause of allergy. In the near future, clinical trials to validate the hypotheses found in this study are desired.

Information on patient quality of life (QOL) is essential to many clinical decisions. Therefore, studies that aim to extract QOL information from patient narratives are increasingly drawing attention. Also, several studies have noted that web services for patients, such as patient social networking services, may represent promising resources for QOL research. However, it is still unclear whether patient narrative text contains corresponding amounts of QOL information as self-reported QOL. This study investigates if medical staff can accurately estimate patient QOL from only patient narrative texts. We analyzed (1) QOL of cancer patients estimated by medical staff from patient autobiographical texts and (2) self-reported QOL scores of cancer patients. We compared patients from the following 3 disease groups: (1) gastrointestinal cancer, (2) breast cancer, and (3) lymphoma. The SF-36v2™ Health Survey was used to measure patient QOL in both materials, and the QOLs were compared. We found significant differences between self-reported QOL and estimated QOL in breast cancer patients and lymphoma patients, but not in gastrointestinal cancer patients. In particular, the medical staff tended to underestimate physical QOL scores. Medical staff may underestimate several aspects of QOL scores. On the basis of these results, we may be able to achieve more precise QOL estimation from patient narratives.

Clostridium difficile-associated disease (CDAD) constitutes a large majority of nosocomial diarrhea cases in industrialized nations and is mediated by the effects of two secreted toxins, toxin A (TcdA) and toxin B (TcdB). Patients who develop strong antitoxin antibody responses can clear C. difficile infection and remain disease free. Key toxin-neutralizing epitopes have been found within the carboxy-terminal receptor binding domains (RBDs) of TcdA and TcdB, which has generated interest in developing the RBD as a viable vaccine target. While numerous platforms have been studied, very little data describes the potential of DNA vaccination against CDAD. Therefore, we created highly optimized plasmids encoding the RBDs from TcdA and TcdB in which any putative N-linked glycosylation sites were altered. Mice and nonhuman primates were immunized intramuscularly, followed by in vivo electroporation, and in these animal models, vaccination induced significant levels of both anti-RBD antibodies (blood and stool) and RBD-specific antibody-secreting cells. Further characterization revealed that sera from immunized mice and nonhuman primates could detect RBD protein from transfected cells, as well as neutralize purified toxins in an in vitro cytotoxicity assay. Mice that were immunized with plasmids or given nonhuman-primate sera were protected from a lethal challenge with purified TcdA and/or TcdB. Moreover, immunized mice were significantly protected when challenged with C. difficile spores from homologous (VPI 10463) and heterologous, epidemic (UK1) strains. These data demonstrate the robust immunogenicity and efficacy of a TcdA/B RBD-based DNA vaccine in preclinical models of acute toxin-associated and intragastric, spore-induced colonic disease., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Enhancement of intestinal IgA responses is a primary strategy in the development of oral vaccine. Dietary fatty acids are known to regulate host immune responses. In this study, we show that dietary palmitic acid (PA) and its metabolites enhance intestinal IgA responses. Intestinal IgA production was increased in mice maintained on a PA-enriched diet. These mice also showed increased intestinal IgA responses against orally immunized Ag, without any effect on serum Ab responses. We found that PA directly stimulates plasma cells to produce Ab. In addition, mice receiving a PA-enriched diet had increased numbers of IgA-producing plasma cells in the large intestine; this effect was abolished when serine palmitoyltransferase was inhibited. These findings suggest that dietary PA regulates intestinal IgA responses and has the potential to be a diet-derived mucosal adjuvant., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Background: The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications., Methods: We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (ClinicalTrials.gov, controlled-trials.com, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis., Results: Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction., Conclusion: The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.

Diamond has the highest known SAW phase velocity, sufficient for applications in the gigahertz range. However, although numerous studies have demonstrated SAW devices on polycrystalline diamond thin films, all have had much larger propagation loss than single-crystal materials such as LiNbO3. Hence, in this study, we fabricated and characterized one-port SAW resonators on single-crystal diamond substrates synthesized using a high-pressure and high-temperature method to identify and minimize sources of propagation loss. A series of one-port resonators were fabricated with the interdigital transducer/ AlN/diamond structure and their characteristics were measured. The device with the best performance exhibited a resonance frequency f of 5.3 GHz, and the equivalent circuit model gave a quality factor Q of 5509. Thus, a large fQ product of approximately 2.9 × 10(13) was obtained, and the propagation loss was found to be only 0.006 dB/wavelength. These excellent properties are attributed mainly to the reduction of scattering loss in a substrate using a single-crystal diamond, which originated from the grain boundary of diamond and the surface roughness of the AlN thin film and the diamond substrate. These results show that single-crystal diamond SAW resonators have great potential for use in low-noise super-high-frequency oscillators.

We demonstrate an absolute magnetometer based on quantum beats in the ground state of nitrogen-vacancy centers in diamond. We show that, by eliminating the dependence of spin evolution on the zero-field splitting D, the magnetometer is immune to temperature fluctuation and strain inhomogeneity. We apply this technique to measure low-frequency magnetic field noise by using a single nitrogen-vacancy center located within 500 nm of the surface of an isotopically pure (99.99% 12C) diamond. The photon-shot-noise limited sensitivity achieves 38  nT/sqrt[Hz] for 4.45 s acquisition time, a factor of sqrt[2] better than the implementation which uses only two spin levels. For long acquisition times (>10  s), we realize up to a factor of 15 improvement in magnetic sensitivity, which demonstrates the robustness of our technique against thermal drifts. Applying our technique to nitrogen-vacancy center ensembles, we eliminate dephasing from longitudinal strain inhomogeneity, resulting in a factor of 2.3 improvement in sensitivity.

Intestinal plasma cells predominantly produce immunoglobulin (Ig) A, however, their functional diversity remains poorly characterized. Here we show that murine intestinal IgA plasma cells can be newly classified into two populations on the basis of CD11b expression, which cannot be discriminated by currently known criteria such as general plasma cell markers, B cell origin and T cell dependence. CD11b(+) IgA(+) plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b(-) IgA(+) plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance. These features allow CD11b(+) IgA(+) plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen. These findings reveal the functional diversity of IgA(+) plasma cells in the murine intestine.

We have studied optical and spin properties of near-surface nitrogen-vacancy (NV) centers incorporated during chemical vapor phase growth of isotopically purified (12)C single-crystal diamond layers. The spectral diffusion-limited line width of zero-phonon luminescence from the NV centers is 1.2 ± 0.5 GHz, a considerable improvement over that of NV centers formed by ion implantation and annealing. Enhanced spin dephasing times (T(2)* ≈ 90 μs, T(2) ≈ 1.7 ms) due to the reduction of (13)C nuclear spins persist even for NV centers placed within 100 nm of the surface., (© 2012 American Chemical Society)

Background: The Japanese Guidelines for the Management of Acute Pancreatitis was published in 2003. However, the impact of the guidelines on physicians' practice patterns has not been well known., Methods: To examine the current clinical practices in the management of acute pancreatitis, we conducted a questionnaire survey with members of three societies involved in the treatment of pancreatic diseases and abdominal emergency medical care. Questions included diagnostic and treatment processes considered important in the management of acute pancreatitis in addition to demographic data, experience in medical care, and areas of specialty of respondents. We also examined changes in the treatment of acute pancreatitis before and after publication of the Guidelines., Results: Of 1,000 society members to whom questionnaires were mailed, 590 responded. Respondents who had read the Guidelines also handled significantly more cases in the most recent 3 years. A variety of changes were observed in the performance of clinical practices before and after publication of the Guidelines. The use of amylase in the assessment of severity decreased significantly, while its use for determination of severity scores increased significantly after publication of the Guidelines. In treatment, use of a nasogastric tube in mild and moderate cases deceased after the Guidelines. The frequency of prophylactic use of antibiotics decreased with mild pancreatitis after publication of the Guidelines., Conclusions: Although it is difficult to attribute these changes to the direct influence of the Guidelines, several changes were observed in performance of clinical practices in accordance with recommendations of the Guidelines.

Clinical indicators set forth in the guidelines have been found to contribute to the improvement in compliance with the guidelines. On the other hand, it has been shown that clinical indicators are more effective when individual indicators are presented in the form of a bundle than when they are given separately. Accordingly, in the JPN Guidelines 2010 for management of acute pancreatitis, those indicators that are judged to be important on the basis of a recommendation classification of "A or B" are presented as a pancreatitis bundle. Each item includes assessment of severity after a diagnosis of pancreatitis has been made, differentiation of pathogenesis, management of gallstone-induced pancreatitis, a sufficient dose of fluid replacement and monitoring, pain control, prophylactic administration of wide-spectrum antibiotics and cholecystectomy following resolution of pancreatic symptoms caused by cholecystolithiasis. Hereafter, the efficacy of these indicators and the significance of their achievement should be examined carefully. Then, the assessment of the compliance rate with the guidelines as well as the assessment of the guidelines and pancreatitis itself should become possible.

The medical insurance system of Japan is based on the Universal Medical Care System guaranteed by the provision of the Article 25 of the Constitution of Japan, which states that "All the people shall have the right to live a healthy, cultural and minimum standard of life." The health insurance system of Japan comprises the medical insurance system and the health care system for the long-lived. Medical care insurance includes the employees' health insurance (Social Insurance) that covers employees of private companies and their families and community insurance (National Health Insurance) that covers the self-employed. Each medical insurance system has its own medical care system for the retired and their families. The health care system for the long-lived covers people of over 75 years of age (over 65 years in people with a certain handicap). There is also a system under which all or part of the medical expenses is reimbursed by public expenditure or the cost of medical care not covered by health insurance is paid by the government. This system is referred to collectively as the "the public payment system of medical expenses." To support the realization of the purpose of this system, there is a treatment research enterprise for specified diseases (intractable diseases). Because of the high mortality rate, acute pancreatitis is specified as an intractable disease for the purpose of reducing its mortality rate, and treatment expenses of patients are paid in full by the government dating back to the day when the application was made for a certificate verifying that he or she has severe acute pancreatitis.

The possibility of using bacteria to drill metallic surfaces has been demonstrated using Staphylococcus sp., a facultative anaerobic bacterium, isolated from corroded copper piping. The experiment involved exposure of copper coupons (25 mm x 15 mm x 3 mm) to a culture of Staphylococcus sp. for a maximum period of 7 days. Coupons exposed to sterile bacterial growth medium were used as controls. Exposed coupons were removed intermittently and observed microscopically for the extent of drilling. The total pit area and volume on these coupons were determined using image analysis. The results showed that both the biomachined area and volume increased with the duration of coupon exposure. In the drilling experiment, a copper thin film 2 microm thick was perforated by this bacterium within a period of 7 days. In conclusion, the results suggested that bacteria can be used as a tool for machining metallic surfaces.

Case 1: A man in his sixties underwent extended right lobectomy of the liver for hepatic hilar cholangiocarcinoma (stage III, fCur B)in July2002. CT scans revealed cancerous pleuritis in March 2005, and he was treated with the chemotherapy of GEM alone as first-line, combined chemotherapy of S-1 and GEM as second-line, and CDDP and GEM as third-line treatment. These therapies have been effective for about 20 months. Case 2: A woman in her sixties was diagnosed with advanced gallbladder cancer(stage IVb)in September 2005. She was given combined chemotherapy of S-1+GEM as first-line, and CDDP+GEM as second-line treatment. The main tumor and metastatic lymph nodes were shrunk, allowing us to perform extended hepatectomy. Histopathologic examinations of the resected specimen of the liver involved by the tumor showed the increased infiltration of inflammatorycells and fibrosis. These patients have been managed on an outpatient basis with good QOL and cancer controlled. Although there has been no established standard regimen, the combined chemotherapy based on GEM will be a provisional standard regimen for patients with advanced biliarytract cancers.

A 71-year-old man underwent right hemicolectomy for an ascending colon cancer (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil was performed, but CT scans and FDG-PET, conducted in May 2003, revealed cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed. Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day; day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed a partial response. Only grade 2 vomiting was noted as an adverse reaction to the treatment, however, the patient has been managed on an outpatient basis for the last 3 years with good QOL and the cancer under control. This case suggests that this combination therapy can be expected to be highly effective as a safe approach for continuously maintaining the QOL of patients with advanced or recurrent colorectal cancer.

Background/purpose: In this study, we conducted a limited survey of reports of surgical randomized controlled trials, using the consolidated standards of reporting trials (CONSORT) statement and additional check items to clarify problems in the evaluation of surgical reports., Methods: A total of 13 randomized trials were selected from two latest review articles on biliary surgery. Each randomized trial was evaluated according to 28 quality measures that comprised items from the CONSORT statement plus additional items. Analysis focused on relationships between the quality of each study and the estimated effect gap ("pooled estimate in meta-analysis" -- "estimated effect of each study")., Results: No definite relationships were found between individual study quality and the estimated effect gap. The following items could have been described but were not provided in almost all the surgical RCT reports: "clearly defined outcomes"; "details of randomization"; "participant flow charts"; "intention-to-treat analysis"; "ancillary analyses"; and "financial conflicts of interest". The item, "participation of a trial methodologist in the study" was not found in any of the reports., Conclusions: Although the quality of reporting trials is not always related to a biased estimation of treatment effect, the items used for quality measures must be described to enable readers to evaluate the quality and applicability of the reporting. Further development of an assessment tool is needed for items specific to surgical randomized controlled trials.

Background: Antiplatelet agents have been widely used in the management of immunoglobulin A (IgA) nephropathy in the Japanese population. To systematically evaluate the effects of antiplatelet agents for IgA nephropathy, we conducted a meta-analysis of the published studies., Methods: Data sources consisted of MEDLINE, EMBASE, the Cochrane Library, Ityu-shi (Japanese medical database), and bibliographies from the studies. The quality of the studies was evaluated from the intention to treat analysis and allocation concealment, as well as by the Jadad method. Meta-analyses were performed on the outcomes of proteinuria and renal function., Results: Seven articles met the predetermined inclusion criteria. The use of antiplatelet agents showed statistically significant effects on proteinuria and renal function. The pooled risk ratio for proteinuria was 0.61 (95% confidence intervals (CI) 0.39-0.94) and for renal function it was 0.74 (95% CI 0.63-0.87)., Conclusions: Antiplatelet agents resulted in reduced proteinuria and protected renal function in patients with IgA nephropathy. However, studies of high-quality design were rare, and most studies assessed surrogate outcomes. More properly designed studies are needed to reach a definitive assessment of this matter.

Objectives: To compare the results of randomized controlled trials versus observational studies in meta-analyses of digestive surgical topics., Summary Background Data: While randomized controlled trials have been recognized as providing the highest standard of evidence, claims have been made that observational studies may overestimate treatment benefits. This debate has recently been renewed, particularly with regard to pharmacotherapies., Methods: The PubMed (1966 to April 2004), EMBASE (1986 to April 2004) and Cochrane databases (Issue 2, 2004) were searched to identify meta-analyses of randomized controlled trials in digestive surgery. Fifty-two outcomes of 18 topics were identified from 276 original articles (96 randomized trials, 180 observational studies) and included in meta-analyses. All available binary data and study characteristics were extracted and combined separately for randomized and observational studies. In each selected digestive surgical topic, summary odds ratios or relative risks from randomized controlled trials were compared with observational studies using an equivalent calculation method., Results: Significant between-study heterogeneity was seen more often among observational studies (5 of 12 topics) than among randomized trials (1 of 9 topics). In 4 of the 16 primary outcomes compared (10 of 52 total outcomes), summary estimates of treatment effects showed significant discrepancies between the two designs., Conclusions: One fourth of observational studies gave different results than randomized trials, and between-study heterogeneity was more common in observational studies in the field of digestive surgery.

Background: To compare single- with two- layer intestinal anastomosis after intestinal resection: a meta-analysis of randomized controlled trials., Methods: Randomized controlled trials comparing single- with two-layer intestinal anastomosis were identified using a systematic search of Medline, Embase and the Cochrane Library Databases covering articles published from 1966 to 2004. Outcome of primary interest was postoperative leak. A risk ratio for trial outcomes and weighted pooled estimates for data were calculated. A fixed-effect model weighted using Mantel-Haenszel methods and a random-effect model using DerSimonian-Laird methods were employed., Results: Six trials were analyzed, comprising 670 participants (single-layer group, n = 299; two-layer group, n = 371). Data on leaks were available from all included studies. Combined risk ratio using DerSimonian-Laird methods was 0.91 (95% CI = 0.49 to 1.69), and indicated no significant difference. Inter-study heterogeneity was significant (chi2 = 10.5, d.f. = 5, p = 0.06)., Conclusion: No evidence was found that two-layer intestinal anastomosis leads to fewer post-operative leaks than single layer. Considering duration of the anastomosis procedure and medical expenses, single-layer intestinal anastomosis appears to represent the optimal choice for most surgical situations.

Purpose: We performed a meta-analysis of randomized controlled trials to determine the optimal timing of laparoscopic cholecystectomy and open cholecystectomy for acute cholecystitis., Methods: We retrieved randomized controlled trials (RCTs) that compared early with delayed cholecystectomy for acute cholecystitis by systematically searching Medline and the Cochrane Library for studies published between 1966 and 2003. The outcomes of primary interest were mortality and morbidity., Results: The ten trials we analyzed comprised 1 014 subjects; 534 were assigned to the early group and 480 assigned to the delayed group. The combined risk difference of mortality appeared to favor open cholecystectomy in the early period (risk difference, -0.02; 95% confidence interval, -0.44 to -0.00), but no differences were found among laparoscopic procedures or among all procedures. The combined risk difference of morbidity showed no differences between the open and laparoscopic procedures. The combined risk difference of the rate of conversion to open surgery showed no differences in the included laparoscopic studies; however, the combined total hospital stay was significantly shorter in the early group than in the delayed group., Conclusions: There is no advantage to delaying cholecystectomy for acute cholecystitis on the basis of outcomes in mortality, morbidity, rate of conversion to open surgery, and mean hospital stay. Thus, early cholecystectomy should be performed for patients with acute cholecystitis.

High-frequency surface acoustic wave (SAW) devices based on diamond that have been realized to date utilize c-axis-oriented ZnO as the piezoelectric thin film. This material, with SiO2 overlay, shows excellent characteristics of a high phase velocity of over 10,000 m/s and a zero temperature coefficient, and it has been successfully applied to high-frequency SAW filters and resonators. To expand on materials used on diamond, the theoretical calculation has been carried out for LiNbO3/diamond, and a high electromechanical coupling coefficient up to 9.0% is expected. In this work, the characteristics of SiO2/LiNbO3/diamond were studied by computer simulation, emphasizing a zero temperature coefficient with a high coupling coefficient. Calculations are carried out for the phase velocity, the electromechanical coupling coefficient, and the temperature coefficient of the Rayleigh wave and its higher mode Sezawa wave. As a result, SiO2/IDT/LiNbO3/diamond is found to offer a zero temperature coefficient with a very high coupling coefficient up to 10.1% in conjunction with a high phase velocity of 12,100 m/s.

Objectives: Protease inhibitors are used to treat acute pancreatitis, but their effectiveness remains unclear. We performed a meta-analysis to determine whether treatment with protease inhibitors reduces overall mortality or morbidity from acute pancreatitis., Methods: Articles of randomized controlled trials evaluating effects of protease inhibitors for acute pancreatitis were retrieved by systematically searching Medline, the Cochrane Library and Journal@ovid databases published from January 1966 through December 2003. References of review articles were also searched manually. The main outcome in interest was the overall mortality rate from acute pancreatitis., Results: Ten studies met the inclusion criteria. Treatment with protease inhibitors did not significantly reduce the mortality rate from acute pancreatitis (pooled risk difference, -0.03; 95% confidence interval, -0.07 to 0.01). Subgroup analyses showed that treatment with protease inhibitors significantly reduced the mortality rate in patients with moderate to severe pancreatitis (pooled risk difference, -0.07; 95% confidence interval, -0.13 to -0.01) as defined by mortality rate in the control group (control mortality rate > 0.10). The decrease in mortality rate was not significant in mild pancreatitis (pooled risk difference, 0.00; 95% confidence interval, -0.04 to 0.05)., Conclusions: Treatment with protease inhibitors does not significantly reduce the mortality in patients with acute or mild pancreatitis, but may reduce the mortality in patients with moderate to severe pancreatitis.

High-frequency surface acoustic wave (SAW) devices based on diamond that have been produced to date utilize the SiO2/ZnO/diamond structure, which shows excellent characteristics of a phase velocity of over 10,000 m/s with a zero temperature coefficient; this structure has been successfully applied to high-frequency narrowband filters and resonators. To expand material systems to wideband applications, c-axis-oriented LiNbO3 on diamond was studied and a coupling coefficient up to 9.0% was estimated to be obtained. In this paper, the characteristics of LiNbO3/diamond with the assumption that the LiNbO3 film is a single crystal have been studied by theoretical calculations to find higher coupling coefficient conditions. Calculations are made for the phase velocity, the coupling coefficient, and the temperature coefficient of the Rayleigh wave and its higher mode Sezawa waves. As a result, LiNbO3/diamond is found to offer a very high electromechanical coupling coefficient of up to 16% in conjunction with a high phase velocity of 12,600 m/s and a small temperature coefficient of 25 ppm/deg. This characteristic is suitable for wide bandwidth applications in high-frequency SAW devices.

A 70-year-old woman was admitted to our hospital for evaluation of a nodular shadow and an apparent cavity in the right middle lung field. Transbronchial biopsy and percutaneous needle biopsy had failed to result in a diagnosis. Serial chest X-ray films revealed slight regression of the nodule without therapy. Pulmonary dirofilariasis was diagnosed after open-lung biopsy and Ouchterlony's double diffusion test. Cavity formation and spontaneous regression are rare in pulmonary dirofilariasis.

The Serratia marcescens serine protease (SSP; 66 kDa) is synthesized as a precursor (preproSSP; 112 kDa) composed of the NH2-terminal signal peptide of 27 amino acids, the mature protease part and a large COOH-terminal domain. When the SSP gene is expressed in Escherichia coli under the control of the tac promoter, the mature enzyme is excreted into the medium through the outer membrane, whereas preproSSP and two proteins, C-1 (40 kDa) and C-2 (38 kDa), processed from the COOH-terminal domain, are accumulated in the membrane fraction. Although treatment of the intact cells with trypsin caused slight truncation of C-1 and C-2, the main parts of C-1 and C-2, both of which are detected in the outer membrane, were resistant to trypsin, even after the cells had been osmotically shocked. Consistent with this, a high content of beta-sheet structure in C-2 was suggested by marked heat-modifiability, as determined by their electrophoretic mobilities on SDS-polyacrylamide gel. These findings suggest rigid integration of C-1 and C-2 in the outer membrane. Upon induction of the tac promoter, rapid excretion of SSP into the medium was first accompanied by the accumulation of C-1 in the outer membrane, which was followed by conversion of C-1 to C-2. PreproSSP was not detected during the accumulation of SSP in the medium, but it was gradually accumulated after the accumulation of SSP had reached a plateau. In addition, preproSSP still containing the intact NH2-terminal signal peptide was completely digested with trypsin when added to osmotically shocked cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The Serratia marcescens serine protease gene encoding a 1,045-amino-acid precursor protein of 112 kDa directs excretion of the mature protease of ca. 58 kDa through the outer membrane of Escherichia coli. A typical signal peptide of 27 amino acids and a large COOH-terminal domain of the precursor are both functionally essential for the excretion of the mature protease into the medium. Sequence analysis of the fragment peptides of the mature protease as well as site-directed mutagenesis indicated that the COOH-terminus of the mature enzyme was Asp645. By using the polyclonal antibody against the 112-kDa precursor protein, not only the intact precursor but also two proteins, C-1 (40 kDa) and C-2 (38 kDa), corresponding to the processed COOH-terminal domains were detected in the insoluble fraction of E. coli cells. Further fractionation by sucrose density gradient centrifugation showed that C-1 and C-2 were localized in the outer membrane. The NH2-terminal residues of C-1 and C-2 were determined to be Ala702 and Phe717, respectively. All these data suggest that the precursor is cleaved at three positions, between Asp645-Ser646, Glu701-Ala702, and Gly716-Phe717, probably by the self-processing activity in the normal excretion pathway through the outer membrane.

Mutarotation of products from p-nitrophenyl beta-D-cellobioside and cellopentaitol by two different types of exo-cellulases from Trichoderma viride was investigated. It was found that an exo-cellulase of glucosidase type produced from the former substrate D-glucose which was mutarotated in a downward direction, while another exo-cellulase of Avicelase type produced from the latter substrate cellobiose which was mutarotated in an upward direction.

Production of polyvinly alcohol (PVA) oxidase by Pseudomonas sp. strain VM15C, a PVA degrader of a symbiotic PVA-utilizing mixed culture, was examined in various cultures. Despite the absence of PVA in the culture in nutrient broth, VM15C showed approximately the same productivity of PVA oxidase activity as that in the culture with PVA as the sole carbon source, whereas the productivity in the culture with glucose was lower than that of either the nutrient broth or the PVA culture. PVA oxidase activity produced in the nutrient broth culture was predominantly present in the cells, and most of the activity appeared to be in the cytoplasm. In contrast, in the culture with PVA as the sole carbon source, the activity was present in the culture fluid in a larger ratio than in the nutrient broth culture. Thus, production of PVA oxidase activity by this strain was constitutive and repressible, although localization of the produced activity was changed by growth conditions.

An enzyme extract from Cellulase-Onozuka, a commercial product of Trichoderma viride, was fractionated by Amberlite CG-50 column chromatography into three cellulase [EC 3.2.1.4] groups, peaks I to III. A noval enzyme, which has both beta-glucosidase [EC 3.2.1.21] and exo-carboxymethyl-cellulase (exo-CMCase) properties was obtained from peak III by extensive purification throuh consecutive column chromatography. The enzyme was homogeneous on ultracentrifugation, SDS-gel and cellulose acetate film electrophoreses and molecular sieve chromatography on Bio-Gel P-150. The molecular weight of this enzyme was estimated to be 53,000. The enzyme appeared to release cellobiose residues one by one from the nonreducing end of higher cellooligosaccharides and CM-cellulose (CMC), but to release glucosyl residues from reduced cellotriose and beta-cellobioside, resembling a beta-glucosidase in this respect. Furthermore, this exo-CMCase also attacked xylan exo-wise to produce xylobiose moleculaes one by one, but it scarcely attacked insoluble cellulose, except for a cellodextrin apparently rich in amorphous structure.

We have succeeded in purifying to homogeneity a very labile NADP+-linked isocitrate dehydrogenase (isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42) from a strain of alkalophilic Bacillus, by a simple method, with an overall yield over 76% of the original activity. The molecular weight on Sephadex G-200 was around 90,000; and that by electrophoresis on SDS-polyacrylamide gels was about 44,000. The sedimentation coefficient (s020,w) and isoelectric point of the enzyme were determined to be 3.22 S and pH 4.7, respectively. The enzyme required Mn2+ for the reaction and for stability. The optimum pH for the reaction was in the range 7.8-8.4 at 30 degrees C; the optimum temperature at pH 8.0 was 75 degrees C; the activation energy of the reaction was 6.2 kcal/mol. The Km values for threo-Ds-isocitrate, DL-isocitrate, and NADP+ were 5.4 microM, 9.9 microM, and 7.3 microM, respectively. This enzyme was inhibited by NADPH, glyceraldehyde 3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, cis-aconitate, alpha-ketoglutarate, and oxaloacetate. In addition, it was subject to a concerted inhibition by a combination of glyoxylate and oxaloacetate, and also to a cumulative inhibition by nucleoside triphosphates.

Fundamental problems of incoherent optical heterodyne detection are analyzed. Output of the heterodyne detection depends on the spatial and temporal coherences of incoming incoherent signal light on the photodetector surface. The directivity of optical heterodyne detection is concluded to be the same as with that of direct detection in an ideal case in which the image of the object is well focused on the photodetector surface. This incoherent heterodyne detection is applied to air pollution monitoring. In the laboratory, the absorption spectra due to NH(3), Freon, and SF(6) are measured using an incoherent light source, and the concentrations of each gas were determined by using the least-squares method.