VARIATION IN RADIATION DOSE RATES FROM RADIONUCLIDES DISCHARGED BY THE SPENT NUCLEAR FUEL REPROCESSING PLANT IN ROKKASHO UNDER DIFFERENT YEARLY WEATHER CONDITIONS.

The radiation dose rate from radionuclides released by the spent nuclear fuel reprocessing plant in Rokkasho, Japan, was assessed for a year specified in the safety review during which the weather conditions were not significantly different from those of the other 10 y. However, the actual year-by-year variation in annual radiation dose rate was not examined. A model system for evaluating the dose rate from the radionuclides released into the atmosphere was constructed. In this study, the radiation dose rate in the weather conditions of 24 weather bins was estimated for a standard year by the model. The annual maximum dose rate from 1959 to 2012 was estimated using a simplified method that integrated the dose rates of each weather bin in the standard year by estimating the annual frequency of the bin in the target year. We obtained ~1.3 as the maximum/minimum ratio of the annual maximum dose rate.

In which cases of pneumonia should we consider treatments for Stenotrophomonas maltophilia?

BACKGROUND: Stenotrophomonas maltophilia is a pathogen commonly associated with respiratory infection. However, the characteristics of pneumonia caused by S. maltophilia remain unknown. AIM: To evaluate the characteristics of and risk factors for S. maltophilia pneumonia. METHODS: A retrospective evaluation was undertaken of 2002 patients with sputum cultures positive for S. maltophilia between January 2010 and December 2019. Cases were excluded based on clinical information and laboratory results. Included cases were divided into two groups: the S. maltophilia pneumonia group (patients with pneumonia caused by S. maltophilia) and the non-S. maltophilia pneumonia group (patients with pneumonia caused by pathogens other than S. maltophilia). Patient characteristics, clinical data and Sequential Organ Failure Assessment (SOFA) scores were compared between the groups. FINDINGS: Eight and 91 patients were assigned to the S. maltophilia pneumonia and non-S. maltophilia pneumonia groups, respectively. The median age was significantly lower in the S. maltophilia pneumonia group than in the non-S. maltophilia pneumonia group (63.4 vs 73.1 years; P<0.01), and the SOFA score was significantly higher in the S. maltophilia pneumonia group (7.5 vs 3.0; P<0.01). Underlying malignancy and pre-administration of antipseudomonal ß-lactams and steroids were confirmed in seven of the eight cases in the S. maltophilia pneumonia group, suggesting an association with immunosuppression. CONCLUSIONS: Pneumonia due to S. maltophilia is a rare occurrence. Treatment for this pathogen should be considered in cases of pneumonia with: (1) predominance of S. maltophilia in sputum cultures; (2) pre-administration of broad-spectrum antibiotics; (3) immunodeficiency; and (4) a high SOFA score.

Alveolar heparan sulfate shedding impedes recovery from bleomycin-induced lung injury.

The pulmonary epithelial glycocalyx, an anionic cell surface layer enriched in glycosaminoglycans such as heparan sulfate and chondroitin sulfate, contributes to the alveolar barrier. Direct injury to the pulmonary epithelium induces shedding of heparan sulfate into the air space; the impact of this shedding on recovery after lung injury is unknown. Using mass spectrometry, we found that heparan sulfate was shed into the air space for up to 3 wk after intratracheal bleomycin-induced lung injury and coincided with induction of matrix metalloproteinases (MMPs), including MMP2. Delayed inhibition of metalloproteinases, beginning 7 days after bleomycin using the nonspecific MMP inhibitor doxycycline, attenuated heparan sulfate shedding and improved lung function, suggesting that heparan sulfate shedding may impair lung recovery. While we also observed an increase in air space heparanase activity after bleomycin, pharmacological and transgenic inhibition of heparanase in vivo failed to attenuate heparan sulfate shedding or protect against bleomycin-induced lung injury. However, experimental augmentation of airway heparanase activity significantly worsened post-bleomycin outcomes, confirming the importance of epithelial glycocalyx integrity to lung recovery. We hypothesized that MMP-associated heparan sulfate shedding contributed to delayed lung recovery, in part, by the release of large, highly sulfated fragments that sequestered lung-reparative growth factors such as hepatocyte growth factor. In vitro, heparan sulfate bound hepatocyte growth factor and attenuated growth factor signaling, suggesting that heparan sulfate shed into the air space after injury may directly impair lung repair. Accordingly, administration of exogenous heparan sulfate to mice after bleomycin injury increased the likelihood of death due to severe lung dysfunction. Together, our findings demonstrate that alveolar epithelial heparan sulfate shedding impedes lung recovery after bleomycin.

A novel endoscopic hydro-mastoidectomy technique for transcanal endoscopic ear surgery.

BACKGROUND: In order to remove a cholesteatoma in the mastoid under transcanal endoscopic ear surgery, it is necessary to perform transcanal endoscopic mastoidectomy. Bone dust and blood, however, obscure the surgical field. A novel endoscopic hydro-mastoidectomy technique was developed, in which the operator performs the mastoidectomy 'underwater' using a lens cleaning system that provides saline perfusion in the surgical space. METHODS: A curved round coarse diamond bur is attached to an otological drill. A lens cleaning sheath is fitted to the endoscope. The surgeon controls the infusion of saline solution by stepping on a footswitch of the power console. RESULTS: Endoscopic hydro-mastoidectomy washes out bone dust and blood from the surgical field, improving the surgical view during mastoidectomy. Additionally, the operator can easily control the flow of saline perfusion. CONCLUSION: This technique provides a clear surgical view by washing out bone dust and blood from the surgical area. The setup for endoscopic hydro-mastoidectomy technique is easy and the operator needs only to buy sheaths if they already own the power console, as many otological and rhinological surgeons do.

Air test as a simple method of screening for Hirschsprung's disease.

AIM: To present the technique and the diagnostic accuracy of the air test to diagnose Hirschsprung's disease (HD). MATERIALS AND METHODS: Children who attended hospital for chronic constipation (CC) between January 2012 and December 2016 for whom the air test was performed were enrolled. The test was conducted during contrast enema under fluoroscopic observation using 20-50 ml injections of air into the rectum through a 10 F Nelaton catheter. The demographics, results of the air test, and additional examinations, as well as the outcomes of subsequent treatments were analysed retrospectively. RESULTS: The air test was conducted in 179 patients (median: 3 years, range: 0-14 years), and was positive in 150 and negative in 29 cases. Of the 29 patients with negative results, four were diagnosed with HD by rectal suction biopsy (RSB). Of the remaining 25 patients, RSB was conducted in seven and HD was excluded in all cases. In all 150 patients with positive air test results, CC was adequately controlled with conservative treatment. The sensitivity and specificity of the air test were 100% (4/4) and 85.7% (150/175), respectively. CONCLUSIONS: The air test can be used as a new non-invasive screening method for HD, performed simultaneously with contrast enema.

ß-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.

Dectin-1 (gene symbol: Clec7a) is a receptor for ß-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a-/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c+/CD11b+ myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a-/- and Il17f-/- mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with ß-glucan-free food. These observations suggest that food-derived ß-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.

Clinical characteristics and outcome of human herpesvirus-6 encephalitis after allogeneic hematopoietic stem cell transplantation.

In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11.09, P<0.001; relative risk in transplantation from HLA-mismatched unrelated donor, 9.48, P<0.001; vs transplantation from HLA-matched related donor) and GvHD prophylaxis by calcineurin inhibitor alone. At 100 days after transplantation, the overall survival rate was 58.3% and 80.5% among patients with and without HHV-6 encephalitis, respectively (P<0.001). Neuropsychological sequelae remained in 57% of 121 evaluated patients. With both foscarnet and ganciclovir, full-dose therapy (foscarnet ⩾180 mg/kg, ganciclovir ⩾10 mg/kg) was associated with better response rate (foscarnet, 93% vs 74%, P=0.044; ganciclovir, 84% vs 58%, P=0.047). HHV-6 encephalitis is not rare not only in cord blood transplant recipients but also in recipients of HLA-mismatched unrelated donors. In this study, development of HHV-6 encephalitis was associated with a poor survival rate, and neurological sequelae remained in many patients.

Surface Protonics Promotes Catalysis.

Catalytic steam reforming of methane for hydrogen production proceeds even at 473 K over 1 wt% Pd/CeO2 catalyst in an electric field, thanks to the surface protonics. Kinetic analyses demonstrated the synergetic effect between catalytic reaction and electric field, revealing strengthened water pressure dependence of the reaction rate when applying an electric field, with one-third the apparent activation energy at the lower reaction temperature range. Operando-IR measurements revealed that proton conduction via adsorbed water on the catalyst surface occurred during electric field application. Methane was activated by proton collision at the Pd-CeO2 interface, based on the inverse kinetic isotope effect. Proton conduction on the catalyst surface plays an important role in methane activation at low temperature. This report is the first describing promotion of the catalytic reaction by surface protonics.

Structural alterations of the superior temporal gyrus in schizophrenia: Detailed subregional differences.

BACKGROUND: Reduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus. METHODS: We acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification. RESULTS: As expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics. CONCLUSIONS: These findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia.

p38γ MAPK is required for inflammation-associated colon tumorigenesis.

Chronic inflammation has long been considered to causatively link to colon cancer development. However, signal transduction pathways involved remain largely unidentified. Here, we report that p38γ mitogen-activated protein kinase mediates inflammatory signaling to promote colon tumorigenesis. Inflammation activates p38γ in mouse colon tissues and intestinal epithelial cell-specific p38γ knockout (KO) attenuates colitis and inhibits pro-inflammatory cytokine expression. Significantly, p38γ KO inhibits tumorigenesis in a colitis-associated mouse model. The specific p38γ pharmacological inhibitor pirfenidone also suppresses pro-inflammatory cytokine expression and colon tumorigenesis. The tumor-promoting activity of epithelial p38γ was further demonstrated by xenograft studies. In addition, p38γ is required for ß-catenin/Wnt activities and p38γ stimulates Wnt transcription by phosphorylating ß-catenin at Ser605. These results show that p38γ activation links inflammation and colon tumorigenesis. Targeting p38γ may be a novel strategy for colon cancer prevention and treatment.

A survival case of severe liver failure caused by acetylsalicylic acid that was treated with living donor liver transplantation.

BACKGROUND: Severe liver dysfunction caused by acetylsalicylic acid (ASA) is quite rare. The purpose is to describe a patient with severe liver dysfunction due to excessive intake of ASA in a suicide attempt, who was successfully treated with living donor liver transplantation (LDLT). DESCRIPTION OF CASE: We report a 20-year-old woman who took 66 g of ASA in a suicide attempt. She was admitted to our hospital and received forced alkaline diuresis. However, her liver and renal functions worsened after admission. On the 6th day after intake of ASA, she was transferred to the intensive care unit, and plasma exchange (PE) and continuous hemodiafiltration were performed. Since her liver function did not recover despite repeated PE, she was transferred to another hospital for LDLT on the 8th day. She underwent LDLT with a portion of the liver donated from her mother on the 11(th) day. After the operation, her renal dysfunction continued. Her renal parameters gradually improved, and she was discharged on the 44th post-operative day without renal dysfunction. CONCLUSION: PE is effective in removing ASA from blood. Liver transplantation is the only effective treatment if liver function does not recover in spite of repeated PE.

Dysregulation of BMI1 and microRNA-16 collaborate to enhance an anti-apoptotic potential in the side population of refractory mantle cell lymphoma.

The proto-oncogene BMI1 and its product, Bmi1, is overexpressed in various types of tumors, particularly in aggressive tumors and tumors resistant to conventional chemotherapy. BMI1/Bmi1 is also crucially involved in cancer-initiating cell maintenance, and is recurrently upregulated in mantle cell lymphoma (MCL), especially aggressive variants. Recently, side population (SP) cells were shown to exhibit tumor-initiating characteristics in various types of tumors. In this study, we show that recurrent MCL cases significantly exhibit upregulation of BMI1/Bmi1. We further demonstrate that clonogenic MCL SP shows such tumor-initiating characteristics as high tumorigenicity and self-renewal capability, and that BMI1 was upregulated in the SP from recurrent MCL cases and MCL cell lines. On screening for upstream regulators of BMI1, we found that expression of microRNA-16 (miR-16) was downregulated in MCL SP cells by regulating Bmi1 in the SPs, leading to reductions in tumor size following lymphoma xenografts. Moreover, to investigate downstream targets of BMI1 in MCL, we performed cross-linking/chromatin immunoprecipitation assay against MCL cell lines and demonstrated that Bmi1 directly regulated pro-apoptotic genes such as BCL2L11/Bim and PMAIP1/Noxa, leading to enhance anti-apoptotic potential of MCL. Finally, we found that a proteasome inhibitor bortezomib, which has been recently used for relapsed MCL, effectively induced apoptosis among MCL cells while reducing expression of Bmi1 and increasing miR-16 in MCL SP. These results suggest that upregulation of BMI1 and downregulation of miR-16 in MCL SP has a key role in the disease's progression by reducing MCL cell apoptosis. Our results provide important new insight into the pathogenesis of MCL and strongly suggest that targeting BMI1/Bmi1 might be an effective approach to treating MCL, particularly refractory and recurrent cases.

Chronic granulomatous disease: two decades of experience from a tertiary care centre in North West India.

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57%) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.

Septic shock caused by Klebsiella oxytoca: An autopsy case and a survival case with driving Extracorporeal Membrane Oxygenation.

We report two cases of Klebsiella oxytoca bacteremia. Case 1 was a 56-year-old man who was transferred to our hospital by ambulance due to diarrhea and general fatigue. On arrival, he was clearly conscious. However he was in septic shock. We injected broad spectrum antibacterial agents and started intensive care. Though intensive care included continuous hemodiafiltration (CHDF), he died 22 hours after admission. Case 2 was a 69-year-old man with a history of gastrectomy for gastric cancer. He had been admitted to a previous hospital due to ileus. His ileus tube was removed on the eighth day, and he then developed a fever of 38 ºC on the following day. He went into shock and became unconscious; he was therefore transferred to our hospital. We diagnosed septic shock and disseminated intravascular coagulation (DIC). We injected broad spectrum antibacterial agents, and recombinant thrombomodulin alpha (rTM). Although he was started in intensive care, his hemodynamics were unstable on the day following admission. Extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pumping (IABP) were started to maintain his hemodynamics. His condition gradually improved, and he was transferred to the previous hospital for rehabilitation on the 28(th) day. ECMO for septic shock in adults is unusual; however ECMO can be introduced even in patients with severe sepsis under careful monitoring. The new anti-DIC agent rTM is useful for safe driving of ECMO in patients with DIC.

Visceral varicella zoster virus infection after allogeneic stem cell transplantation.

INTRODUCTION: Varicella zoster virus (VZV) disease is one of the major infectious complications that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Many reports have shown visceral VZV infection, a special type of VZV disease, to be rare. However, few studies so far have included a large number of patients. FINDINGS: Visceral VZV infection was found in 20 (0.8%) of 2411 patients who underwent allo-HSCT at our hospitals. Seventeen (85%) patients were taking immunosuppressive agents at the time of presentation with zoster. The presenting symptom was abdominal pain in 16 patients (80%), unconsciousness in 3 patients (15%), and no symptoms in 1 patient. The mean time interval from allo-HSCT to symptomatic visceral VZV infection was 273 days (103-800 days). The eruptions appeared within 3 days (0-13) after the first symptoms. Treatment with intravenous acyclovir was initiated before the appearance of eruptions in 3 of 18 patients (all 3 survived) with vesicular eruptions, the same day in 12 patients (11 survived, 1 died), and after the appearance in 3 patients (1 survived, 2 died). The overall mortality was 20%. CONCLUSION: In conclusion, these data confirm that the incidence of visceral VZV infection is infrequent, but this disease is serious. When patients being treated with immunosuppressive agents demonstrate abdominal pain or unconsciousness, the possibility of visceral VZV infection should be considered as well as earlier therapeutic intervention.

Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation.

OBJECTIVES: Micafungin (MCFG) is an antifungal agent that is widely used for the treatment of invasive fungal infection. Although the pharmacokinetics of MCFG is considered to depend on the hepatic metabolism, the impact of hepatic function on the pharmacokinetics of MCFG has been inconsistent among previous studies. The object of this study was to evaluate the relationship between plasma MCFG concentration and clinical and laboratory data. PATIENTS AND METHODS: We examined the plasma concentration of MCFG in 10 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). MCFG at 150 mg/day was administered intravenously a median of 58.5 days after HSCT. Trough and peak concentrations of MCFG (Cmin and Cmax) were measured at a median of 5.5 days after the first administration of MCFG. RESULTS: The presence of graft-versus-host disease involving the liver at blood sampling was associated with significantly higher Cmin and Cmax of MCFG. Among the laboratory data, Cmin and Cmax were significantly higher in patients with severely impaired hepatic function defined as serum total bilirubin (TBi) level >5 mg/dL and/or serum gamma-glutamyltransferase (γ-GTP) level >500 IU/L, but the presence of mildly impaired hepatic function defined as serum TBi level >2 mg/dL and/or serum γ-GTP level >200 IU/L did not affect Cmin and Cmax. Renal function did not show significant impact on Cmin and Cmax. CONCLUSION: These findings suggest that the pharmacokinetics of MCFG is affected only by severely impaired liver function.

Hyperbilirubinemia in the early phase after allogeneic HSCT: prognostic significance of the alkaline phosphatase/total bilirubin ratio.

Hyperbilirubinemia in the early phase after allogeneic hematopoietic SCT (HSCT) is due to various causes. One of the most important causes of hyperbilirubinemia is veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS). However, the prognosis of patients who are clinically diagnosed as SOS varies. We retrospectively evaluated 82 patients who underwent their first allogeneic HSCT. GVHD prophylaxis was a combination of short-term MTX and CsA (n=77) or tacrolimus (n=5). Thirty-three patients developed hyperbilirubinemia, with a bilirubin level of at least 2 mg/dL, within 20 days after HSCT. Of these patients, 24 were diagnosed as VOD/SOS using the modified Seattle criteria. Twenty-six recovered to a bilirubin level of <2 mg/dL. We focused on the serum alkaline phosphatase/total bilirubin ratio (ALP/TB) at the onset of hyperbilirubinemia and found that it significantly predicted the recovery from hyperbilirubinemia. OS was significantly higher in patients with a lower ALP/TB ratio (P=0.00056). In addition, a lower ALP/TB ratio was associated with better survival even in patients who were clinically diagnosed as SOS (P<0.001). The ALP/TB ratio at the onset of hyperbilirubinemia may be a useful predictor for the prognosis of hyperbilirubinemia and SOS early after HSCT.

Prediction of transplant-related complications by C-reactive protein levels before hematopoietic SCT.

Various biomarkers have been investigated with regard to their ability to predict the outcome of allogeneic hematopoietic SCT (HSCT). In this study, we retrospectively reviewed 90 recipients who received HSCT between 2007 and 2011 in our institution, and evaluated the predictive value of the baseline serum C-reactive protein (CRP) levels just before the initiation of conditioning for transplant-related complications after allogeneic HSCT. A receiver-operating characteristic curve revealed that the baseline serum CRP levels had an excellent predictive value for non-relapse mortality (NRM), with an area under the curve of 0.83. The sensitivity and specificity for NRM were 80% and 87%, respectively, with a cutoff of 0.6 mg/dL. With this cutoff value, multivariate analyses revealed that a higher baseline CRP level was an independent risk factor for NRM (HR 6.21, P<0.01), grade III-IV acute GVHD (HR 3.91, P=0.03) and poor overall survival (HR 3.27, P=0.0018). On the other hand, the baseline CRP level did not predict infectious events. These findings suggested that CRP levels before conditioning may be a useful predictive biomarker for poor survival.