Topical erythritol combined with L-ascorbyl-2-phosphate inhibits staphylococcal growth and alleviates staphylococcal overgrowth in skin lesions of canine superficial pyoderma.

Erythritol (ERT) and L-ascorbyl-2-phosphate (APS) are bacteriostatic, but their effects on staphylococcal skin infections remain unknown. We aimed to determine whether ERT combined with APS inhibits the growth of staphylococci that are commonly isolated from pyoderma skin lesions in dogs. We investigated the individual and combined effects of ERT and APS on the growth of Staphylococcus pseudintermedius, S. schleiferi, and S. aureus using turbidity assays in vitro. Skin lesions from 10 dogs with superficial pyoderma were topically treated with 5% ERT and 0.1% APS for 28 days, and swabbed skin samples were then analyzed using 16S rRNA amplicon sequencing and quantitative real-time PCR (qPCR). Results showed that ERT inhibited S. pseudintermedius growth regardless of harboring the mecA gene, and APS increased the inhibitory effects of ERT against S. pseudintermedius, S. schleiferi, and S. aureus in vitro. Moreover, combined ERT and APS decreased the prevalence of staphylococci on canine skin lesions at the genus level. The combination slightly increased the α-diversity but did not affect the ß-diversity of the microbiota. The qPCR results revealed that the combination significantly decreased S. pseudintermedius and S. schleiferi in skin lesions. Topical administration of EPS combined with APS can prevent staphylococcal colonization on the surface of mammalian skin. The results of this study may provide an alternative to systemic antibiotics for treating superficial pyoderma on mammalian skin surfaces.

Reopening of ductus arteriosus in idiopathic premature constriction or closure of ductus arteriosus: A case series.

BACKGROUND: There is no consensus on managing pregnancy when the fetus is diagnosed with idiopathic premature constriction or closure of the ductus arteriosus (PCDA). Knowing whether the ductus reopens is valuable information for managing idiopathic PCDA. We conducted a case-series study to investigate the natural perinatal course of idiopathic PCDA and examined factors associated with ductal reopening. METHODS: We retrospectively collected information about the perinatal course and echocardiographic findings at our institution, which, on principle, does not determine delivery timing based on fetal echocardiographic results. We also examined perinatal factors related to the reopening of the ductus arteriosus. RESULTS: Thirteen cases of idiopathic PCDA were included in the analysis. The ductus reopened in 38% of cases. Among cases diagnosed in < 37 weeks of gestation, 71% reopened, which was confirmed seven days after diagnosis (interquartile range 4-7). Diagnosis earlier in gestation was associated with ductal reopening (p = 0.006). Two cases (15%) developed persistent pulmonary hypertension. No fetal hydrops or death occurred. CONCLUSIONS: The ductus is likely to reopen when prenatally diagnosed before 37 weeks gestation. There were no complications due to our pregnancy management policy. In idiopathic PCDA, especially if the prenatal diagnosis is made before 37 weeks of gestational age, continuing the pregnancy with careful monitoring of the fetus's well-being is recommended.

Exopolysaccharides from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 prevent influenza virus infection and attenuate secondary bacterial infection risk.

The present study assessed the inhibitory action of exopolysaccharides (EPS) produced by Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 against influenza virus infection followed by secondary bacterial infection. We found that the presence of 200 or 400 µg ml-1 of EPS significantly protected against influenza virus infection in a dose-dependent manner when A549 cells were treated with EPS before infection but not after it. The expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1), an adhesion molecule for bacteria adherence, on A549 cells was significantly enhanced during influenza virus infection compared with viral-non-infected A549 cells. However, this upregulated CEACAM-1 expression was significantly decreased by EPS treatment before viral infection in association with the reduction in the virus titre in A549 cells. In a bacterial adhesion assay using Staphylococcus aureus, the bacterial adherence to viral-infected A549 cells was significantly greater than that to viral-non-infected A549 cells, and the increased bacterial adherence induced by influenza virus infection tended to be decreased by EPS treatment before the infection. Our findings show that EPS treatment before viral infection can inhibit influenza virus infection and alleviate secondary bacterial infection through decreased CEACAM-1 expression.

Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypical femoral fractures in patients with rheumatoid arthritis.

The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.

Presenteeism among workers: health-related factors, work-related factors and health literacy.

BACKGROUND: Presenteeism is an important factor in workers' health. However, few studies have examined how variables such as socio-economic status, health status, workplace status and health literacy correlate with and affect presenteeism. AIMS: To assess the correlates of presenteeism with a focus on health-related factors, work-related factors and health literacy. METHODS: We conducted a cross-sectional study of 2914 Japanese workers from one company. We used a self-administered questionnaire to assess socio-demographic characteristics, health status, work environment, presenteeism and health literacy. RESULTS: Forty-one per cent of participants were under 40 years of age and 70% were male. We found that 59% of the participants were at high risk of presenteeism. Presenteeism was associated with sex, age, household income, marital status, health-related factors (i.e. self-rated health status, dietary choices, exercise habits), work-related factors (i.e. workplace support, job demands, job control) and health literacy. Logistic regression analyses indicated that presenteeism was associated with self-rated health status, overtime hours, workplace support, job demands, job control and health literacy after adjusting for sex, age and income. CONCLUSIONS: Health-related factors, work-related factors and health literacy are all associated with presenteeism. Improving the workplace environment, especially factors such as overtime working hours, workplace support, job demands and job control, and increasing health literacy may reduce presenteeism among general office workers.

Record-high sensitivity compact multi-slot sub-wavelength Bragg grating refractive index sensor on SOI platform.

In this paper, a high sensitivity compact multi-slot sub-wavelength Bragg grating refractive index (RI) sensor was investigated. The structural parameters were optimized for higher sensitivity to RI change of the surrounding medium from viewpoints of a wavelength shift, an extinction ratio and a transmission loss, and a record-high sensitivity was experimentally demonstrated with a compact size. In this sensor, the first side-lobe at the Bragg grating (BG) stop-band end was focused as a sensing peak wavelength for moderate transmission loss and efficient sensing. To realize the compactness, a period count of the BG was kept as small as 20. By increasing the RI of the surrounding medium, the sensing peak shifts toward a longer wavelength side; thus due to the high sharpness and easy tracing of the first side-lobe, the device worked as an efficient RI sensor. The structural optimization was carried out by using 3D finite-difference time-domain (FDTD) simulation approach, and also influences of the structural parameters to sensitivities were discussed. Based on these optimized parameters, the devices were fabricated using the lift-off technique. By exposing the sensor to various liquid samples with different RIs such as pure water, sugar-dissolved water with various concentrations, acetone and isopropyl alcohol (IPA), a record-high sensitivity of 730 nm/RIU was attained for a sensor fabricated on SOI platforms with a length of as small as 9.5 µm and a transmission loss of 3 dB.

Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

BACKGROUND: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS: The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. RESULTS: The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. CONCLUSION: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.

ANTECEDENTES: La quimioterapia intraperitoneal con paclitaxel se considera una terapia experimental para el tratamiento de la carcinomatosis peritoneal. Este estudio tuvo como objetivo determinar la dosis recomendada y evaluar la eficacia clínica y la seguridad de la combinación de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal en pacientes con cáncer de páncreas y metástasis peritoneales. MÉTODOS: Se evaluaron las frecuencias de las toxicidades limitantes de la dosis, y la dosis recomendada se determinó en la fase I. El objetivo principal de la fase II fue la tasa de supervivencia global a 1 año. Los objetivos secundarios fueron los efectos antitumorales, los efectos de alivio de los síntomas, la seguridad y la supervivencia global. RESULTADOS: Las dosis recomendadas de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal fueron de 800, 75 y 20 mg/m2 , respectivamente. De los 46 pacientes incluidos en la fase II del estudio, la mediana de tiempo hasta el fracaso del tratamiento fue de 6,0 meses (rango, 0-22,6). Las tasas de respuesta y de control de la enfermedad fueron del 45% y 95%, respectivamente. La ascitis desapareció en el 40% de los pacientes, y la citología se negativizó en el 39% de los pacientes. La mediana del tiempo de supervivencia fue de 14,5 meses y la tasa de supervivencia global a 1 año del 60,9%. La cirugía de rescate se realizó en ocho (17%) pacientes, y los que se sometieron a cirugía sobrevivieron significativamente más tiempo que los que no fueron tratados quirúrgicamente (mediana de supervivencia no alcanzada versus 12,4 meses). Las toxicidades hematológicas de grado 3/4 ocurrieron en el 76% de los pacientes, mientras que los eventos adversos no hematológicos se presentaron en el 15% de los pacientes. CONCLUSIÓN: Agregar paclitaxel intraperitoneal tuvo eficacia clínica con una tolerabilidad aceptable. (UMIN000018878).

Spin waves and spin-state transitions in a ruthenate high-temperature antiferromagnet.

Ruthenium compounds serve as a platform for fundamental concepts such as spin-triplet superconductivity1, Kitaev spin liquids2-5 and solid-state analogues of the Higgs mode in particle physics6,7. However, basic questions about the electronic structure of ruthenates remain unanswered, because several key parameters (including Hund's coupling, spin-orbit coupling and exchange interactions) are comparable in magnitude and their interplay is poorly understood, partly due to difficulties in synthesizing large single crystals for spectroscopic experiments. Here we introduce a resonant inelastic X-ray scattering (RIXS)8,9 technique capable of probing collective modes in microcrystals of 4d electron materials. We observe spin waves and spin-state transitions in the honeycomb antiferromagnet SrRu2O6 (ref. 10) and use the extracted exchange interactions and measured magnon gap to explain its high Néel temperature11-16. We expect that the RIXS method presented here will enable momentum-resolved spectroscopy of a large class of 4d transition-metal compounds.

Quantitative assessment of outer retinal folds on enface optical coherence tomography after vitrectomy for rhegmatogenous retinal detachment.

We aimed to investigate the possible causes of metamorphopsia for rhegmatogenous retinal detachment (RRD) based on findings of enface optical coherence tomography (OCT). The study was a retrospective, consecutive case series of 33 eyes with macula-off RRD. Metamorphopsia was measured by M-CHARTS and enface OCT images covering a macular area of 6 × 6 mm square obtained at 1, 3, and 6 months postoperatively. Within the outer retinal slabs of enface OCT, multiple lines that looked like folds were delineated in all eyes at month 1, and we succeeded in extracting images of folds by subtracting retinal vessels. We calculated their density by an image-processing technique. The mean M-CHARTS scores were 0.62 ± 0.47 at month 1 and 0.30 ± 0.29 at month 6 (P < 0.001). The fold density was 8.3 ± 4.2 at month 1 and 6.1 ± 3.1 at month 6 (P = 0.0044). The M-CHARTS scores at 6 months were significantly associated with the fold density at 1 month (r = 0.515, P = 0.002). In conclusion, enface OCT visualized the outer retinal folds in eyes that had undergone successful RRD surgery, and a larger number of folds was related to the remaining metamorphopsia.

Long-term Follow-up of Laparoscope-Assisted Living Donor Hepatectomy.

BACKGROUND: We have introduced and performed laparoscope-assisted surgery in living donor hepatectomy. The objective of this study was to investigate the long-term results of laparoscope-assisted living donor hepatectomy. METHODS: From 2006 to 2016, laparoscope-assisted living donor hepatectomy was performed in 11 patients (laparoscopic group), and conventional open living donor hepatectomy was performed in 40 patients (conventional group). Intraoperative and postoperative complications were evaluated according to the Clavien-Dindo classification and analyzed in the laparoscopic group for comparison with the conventional group. RESULTS: The median postoperative follow-up period was 88 months (range, 58-120 months) in the laparoscopic group. One donor in the conventional group died from a motor vehicle crash 16 months after surgery. All others were alive and returned to their preoperative activity level. Regarding intraoperative and early (≤90 days after surgery) postoperative complications, 1 patient (1/11, 9%) showed biliary fistula (Grade IIIa) in the laparoscopic group. In the conventional group, 6 patients (6/40, 15%) showed surgical complications of Grade I in 2 patients and Grade II in 4 patients. Regarding late (>90 days after surgery) postoperative complications, biliary stricture was observed in 1 patient of the laparoscopic group; this patient developed hepatolithiasis 6 years after surgery, and endoscopic lithotomy and extracorporeal shockwave lithotripsy were performed, resulting in successful treatment. Late complications were not observed in the conventional group. CONCLUSION: One donor in the laparoscopic group showed Grade IIIa late complications. The introduction of laparoscopic surgery to living donor hepatectomy should be performed carefully.

A case of laboratory cross-contamination of Mycobacterium tuberculosis identified using comparative genomics.

BACKGROUND: Two false-positive tuberculosis (TB) cases in Yamagata Prefecture, Japan, 2016. OBJECTIVE: To report the effectiveness of comparative genomics of Mycobacterium tuberculosis for identification of cross-contamination cases. DESIGN: Case report of laboratory cross-contamination. RESULTS: Beginning with detection of an identical genotype in two M. tuberculosis strains using variable number of tandem repeat typing, we suspected M. tuberculosis cross-contamination of specimens collected in a mycobacteriology laboratory based on epidemiological investigations. This suspicion was confirmed using comparative genomics of the two M. tuberculosis strains and a strain from an epidemiologically unrelated specimen from the same batch as the two strains in the mycobacteriology laboratory. All strains had an identical genomic sequence with no single nucleotide variants. CONCLUSION: Comparative genomics, which offers the highest discrimination power, is a potent tool for identifying laboratory cross-contamination using epidemiological investigations.

Endovascular Treatment for Very Early Hepatic Artery Stenosis Following Living-Donor Liver Transplantation: Report of Two Cases.

BACKGROUND: Some literature has reported on endovascular treatment for very early hepatic artery stenosis (HAS; within 2 weeks after liver transplantation, and has deemed endovascular treatment to be a contraindication because out of serious complications associated with the procedure. We report on 2 cases of very early HAS successfully treated with endovascular treatment after living-donor liver transplantation (LDLT). CASE 1: A 54-year-old woman underwent LDLT with a left liver graft. The native right gastric artery and left hepatic artery (LHA) of the donor were anastomosed. On postoperative day (POD) 13, HAS was suspected and multidetector computerized tomographic angiography (MDCTA) was performed, which revealed 90% stenosis of the arterial anastomosis and 50% stenosis of the LHA in the graft. We performed percutaneous balloon arterioplasty (PBA) without any complications. The artery was patent with a postoperative follow-up of 60 months without the need for repeat intervention. CASE 2: A 67-year-old woman with a history of repeated transarterial chemoembolization for hepatocellular carcinoma underwent LDLT with a left liver graft. The native A4 and LHA of the donor were anastomosed. We performed MDCTA on POD 11, which revealed 70% stenosis of the native hepatic artery. We performed PBA followed by stent placement on POD 11 without complication. The artery was patent with a postoperative follow-up of 40 months without the need for repeated intervention. CONCLUSIONS: Endovascular treatment has the potential to avoid the need for repeated surgical interventions or retransplantation, and it can be safely performed in carefully selected patients.

Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations.

Azoospermia affects up to 1% of adult men. Non-obstructive azoospermia is a multifactorial disorder whose molecular basis remains largely unknown. To date, mutations in several genes and multiple submicroscopic copy-number variations (CNVs) have been identified in patients with non-obstructive azoospermia. The aim of this study was to clarify the contribution of nucleotide substitutions in known causative genes and submicroscopic CNVs in the genome to the development of non-obstructive azoospermia. To this end, we conducted sequence analysis of 25 known disease-associated genes using next-generation sequencing and genome-wide copy-number analysis using array-based comparative genomic hybridization. We studied 40 Japanese patients with idiopathic non-obstructive azoospermia. Functional significance of molecular alterations was assessed by in silico analyses. As a result, we identified four putative pathogenic mutations, four rare polymorphisms possibly associated with disease risk, and four probable neutral variants in 10 patients. These sequence alterations included a heterozygous splice site mutation in SOHLH1 and a hemizygous missense substitution in TEX11, which have been reported as causes of non-obstructive azoospermia. Copy-number analysis detected five X chromosomal or autosomal CNVs of unknown clinical significance, in addition to one known pathogenic Y chromosomal microduplication. Five patients carried multiple molecular alterations. The results indicate that monogenic and oligogenic mutations, including those in SOHLH1 and TEX11, account for more than 10% of cases of idiopathic non-obstructive azoospermia. Furthermore, this study suggests possible contributions of substitutions in various genes as well as submicroscopic CNVs on the X chromosome and autosomes to non-obstructive azoospermia, which require further validation.

Crossreactivity of an Antiserum Directed to the Gram-Negative Bacterium Neisseria gonorrhoeae with the SNARE-Complex Protein Snap23 Correlates to Impaired Exocytosis in SH-SY5Y Cells.

Early maternal infections with Neisseria gonorrhoeae (NG) correlate to an increased lifetime schizophrenia risk for the offspring, which might be due to an immune-mediated mechanism. Here, we investigated the interactions of polyclonal antisera to NG (α-NG) with a first trimester prenatal brain multiprotein array, revealing among others the SNARE-complex protein Snap23 as a target antigen for α-NG. This interaction was confirmed by Western blot analysis with a recombinant Snap23 protein, whereas the closely related Snap25 failed to interact with α-NG. Furthermore, a polyclonal antiserum to the closely related bacterium Neisseria meningitidis (α-NM) failed to interact with both proteins. Functionally, in SH-SY5Y cells, α-NG pretreatment interfered with both insulin-induced vesicle recycling, as revealed by uptake of the fluorescent endocytosis marker FM1-43, and insulin-dependent membrane translocation of the glucose transporter GluT4. Similar effects could be observed for an antiserum raised directly to Snap23, whereas a serum to Snap25 failed to do so. In conclusion, Snap23 seems to be a possible immune target for anti-gonococcal antibodies, the interactions of which seem at least in vitro to interfere with vesicle-associated exocytosis. Whether these changes contribute to the correlation between maternal gonococcal infections and psychosis in vivo remains still to be clarified.

Beneficial effects of Lactobacillus casei strain Shirota on academic stress-induced sleep disturbance in healthy adults: a double-blind, randomised, placebo-controlled trial.

The present study examined whether Lactobacillus casei strain Shirota (LcS) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy 4th year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a national standardised examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. Study measures included subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. These findings suggest that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.

Prognostic heterogeneity of the seventh edition of UICC Stage III gallbladder carcinoma: Which patients benefit from surgical resection?

BACKGROUND: This study sought to evaluate the prognostic heterogeneity of Stage III (Union for International Cancer Control, seventh edition) gallbladder carcinoma. METHODS: Of 175 patients enrolled with gallbladder carcinoma who underwent radical resection, 22 were classified with Stage IIIA disease (T3N0M0) and 46 with Stage IIIB disease (T2N1M0 [n = 23] and T3N1M0 [n = 23]). The median number of retrieved lymph nodes per patient was 18. RESULTS: This staging system failed to stratify outcomes between Stages IIIA and IIIB; survival after resection was better for patients with Stage IIIB disease than for patients with Stage IIIA disease, with 5-year survival of 54.9% and 41.0%, respectively (p = 0.366). Multivariate analysis for patients with Stage III disease revealed independently better survival for patients with T2N1M0 than for patients with T3N0M0 (p = 0.016) or T3N1M0 (p = 0.001), with 5-year survival of 77.0%, 41.0%, and 31.0%, respectively. When N1 status was subdivided according to the number of positive nodes, 5-year survival in patients with T2M0 with 1-2 positive nodes, T2M0 with ≥3 positive nodes, T3M0 with 1-2 positive nodes, and T3M0 with ≥3 positive nodes was 83.3%, 50.0%, 45.8%, and 0%, respectively (p < 0.001). CONCLUSIONS: The prognosis of T2N1M0 disease was better than that of T3N0/1M0 disease, suggesting that not all node-positive patients will have uniformly poor outcomes after resection of gallbladder carcinoma. T2M0 with 1-2 positive nodes leads to a favorable outcome after resection, whereas T3M0 with ≥3 positive nodes indicates a dismal prognosis.

What is a typical optic nerve head?

Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.

Development of an E-learning System for the Endoscopic Diagnosis of Early Gastric Cancer: An International Multicenter Randomized Controlled Trial.

BACKGROUND: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness. METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results. FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001). INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

Study of Immune Tolerance Cases in Adult Living Donor Liver Transplantation.

BACKGROUND: Complete immune tolerance is the chief goal in organ transplantation. This study aimed to evaluate patients who successfully withdrew from immunosuppressive (IS) agents after living donor liver transplantation (LDLT). MATERIALS AND METHODS: A retrospective review of all adult LDLT from July 1999 to March 2012 was conducted. In patients who acquired immune tolerance after LDLT, their background and the course of surgical procedures were evaluated. RESULTS: Of a total of 101 adult LDLT patients, 8 patients were completely free of IS agents. Six of these patients (75%) were female, and the median age at the time of transplantation was 56 years (range, 31-66 years). The primary disease causing liver failure was type C liver cirrhosis (50%), fulminant hepatitis (25%), type B liver cirrhosis (12%), and alcoholic liver cirrhosis (12%). The median Child-Pugh score and MELD score were 13 points (range, 8-15 points) and 19 points (range, 10-18 points), respectively. The living related donor was the recipient's child (75%), sibling (12%), or parent (12%). ABO compatibility was identical in 62%, compatible in 25%, and incompatible in 12%. CONCLUSIONS: In this study, we evaluated the adult patients who successfully withdrew from IS agents after LDLT. In most cases, it took more than 5 years to reduce IS agents. Because monitoring of the serum transaminase level is not adequate to detect chronic liver fibrosis in immune tolerance cases, further study is required to find appropriate protocols for reducing IS agent use after LDLT.