Clinical Features of Cytotoxic Lesions of the Corpus Callosum Associated with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Patients with SAH due to a ruptured intracranial aneurysm occasionally show reversible high-signal lesions in the splenium of the corpus callosum on DWI. These lesions are called cytotoxic lesions of the corpus callosum. This study retrospectively reviewed cases of aneurysmal SAH and investigated clinical features of cytotoxic lesions of the corpus callosum associated with SAH. MATERIALS AND METHODS: Participants comprised 259 patients with aneurysmal SAH who had undergone curative treatment at our hospital. We examined the following items related to cytotoxic lesions of the corpus callosum: occurrence rate, timing of appearance and disappearance of the lesions, lesion size, aneurysm location, severity of SAH, treatment method, clinical course, and outcome. RESULTS: Among the 259 cases, DWI detected cytotoxic lesions of the corpus callosum in 33 patients (12.7%). The mean periods from the onset of SAH to detection and disappearance of cytotoxic lesions of the corpus callosum were 6.3 days (range, 0-25 days) and 35.7 days (range, 9-78 days), respectively. Cytotoxic lesions of the corpus callosum were classified into 2 types: a small type localized in the splenium in 26 cases (78.9%) and a large type spread along the ventricle in 7 cases (21.2%). The severity of SAH, coiling, hydrocephalus, and poor mRS score at discharge were significantly higher in the group with cytotoxic lesions of the corpus callosum. However, multivariate analysis did not identify cytotoxic lesions of the corpus callosum as a risk factor for poor outcome. CONCLUSIONS: Cytotoxic lesions of the corpus callosum appear at a frequency of 12.7% in patients with aneurysmal SAH. Cytotoxic lesions of the corpus callosum associated with SAH take several days to appear and subsequently resolve within about a month. Cytotoxic lesions of the corpus callosum were likely to occur in patients with high-grade SAH but did not represent a predictor of poor outcome.

UVA-activated riboflavin promotes collagen crosslinking to prevent root caries.

Root caries is an increasingly problem in aging societies with severe implications for the general health and wellbeing of large numbers of people. Strengthening type-I collagen, a major organic component of human dentin, has proved effective in preventing root caries. This study sought to determine whether exposure to riboflavin followed by UVA irradiation (RF/UVA) could promote additional collagen crosslinking, and thus improve the acid and enzymatic resistance of human dentin under simulated oral environments. If so, it could offer potential for treatment of the intractable problem of root caries. The greatest flexural strengths were found in dentin exposed to a 0.1% riboflavin solution for 1 minute followed by 1,600 mW/cm2 UVA irradiation for 10 minutes. Mineral loss and lesion depth were significantly lower in the RF/UVA group than in the control group. The microstructures of dentinal tubules and collagen networks after RF/UVA treatment retained their original forms after acidic and enzymatic degradation. In conclusion, RF/UVA treatment may be a new method for preventing root caries with promising prospects for clinical application.

Association of preoperative inflammation-based prognostic score with survival in patients undergoing salvage esophagectomy.

Salvage esophagectomy (SALV) is potentially beneficial for patients with residual or relapsed esophageal carcinoma after definitive chemoradiotherapy (dCRT), although preoperatively identifying good candidates for SALV remains difficult. We investigated the prognostic impacts of inflammatory and nutritional status in patients undergoing SALV after dCRT. Forty-seven SALV patients were retrospectively reviewed, of whom 46 (98%) had squamous cell carcinoma and 1 (2%) adenocarcinoma. Possible prognostic factors included patients' demographic data, physical status, blood chemistry profiles, and clinical/pathological tumor features. The Glasgow prognostic score (GPS) was derived from preoperative C-reactive protein (CRP) and albumin values. Thirty (64%), 11 (23%), and 6 (13%) patients were classified into the GPS 0, 1, and 2, respectively, groups. None of the possible prognostic factors showed significant correlations with GPS. Patients with GPS 0 had better outcomes than those with GPS 1 or GPS 2 (Median survivals: 37.8, 15.9, and 5.1 months, respectively, P < 0.001). In the multivariable Cox proportional hazards model, GPS 1 (HR 5.62, 95% CI 1.94-16.4, P = 0.002), GPS 2 (HR 9.10, 95% CI 2.60-31.8, P < 0.001), R1/2 resection (HR 16.3, 95% CI 3.62-86.7, P < 0.001) and incomplete response to dCRT (HR 3.53, 95% CI 1.12-12.5, P = 0.03) were all independent risk factors for a poor outcome. Preoperative GPS is potentially useful for predicting outcomes in esophageal cancer patients undergoing SALV.

Endothelial-derived endothelin-1 promotes pulmonary vascular remodeling in bleomycin-induced pulmonary fibrosis.

Endothelin-1 (ET-1) induces pulmonary vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. Given that endothelial cells are the main source of ET-1 and ET-1 from other cells may encounter difficulty penetrating vascular compartments, we hypothesize that endothelial-derived ET-1 promotes vascular remodeling secondary to pulmonary fibrosis. We used vascular endothelial ET-1 knock-out (VEETKO) and Wild type mice for this research. They were given intratracheal bleomycin and euthanized at day 28. We quantified pulmonary fibrosis, measured lung ET-1 and its receptors' expression, and assessed pulmonary vascular remodeling by calculating medial wall index, muscularization index, adventitial collagen and adventitial fibroblast and macrophage accumulation. Right ventricle remodeling was also assessed. Both VEETKO and Wild type mice developed comparable pulmonary fibrosis and similar fibrosis-related gene expression. Compared to Wild type mice, bleomycin-induced VEETKO mice had lower ET-1 peptide levels (15.4 pg/mg vs. 31.2 pg/mg, p<0.01). Expression of both ET-1 receptors mRNAs were increased in fibrosis models. Bleomycin-induced fibrosis VEETKO mice had significantly less muscularized arterioles, lower muscularization index and attenuated adventitial collagen, fibroblast and macrophage accumulation as compared to that of Wild type mice. Right ventricular pressure, hypertrophy and fibrosis did not increase both in VEETKO and Wild type mice despite the more enhanced vascular remodeling in Wild type. In conclusion, endothelial-derived endothelin-1 promotes pulmonary vascular remodeling secondary to bleomycin-induced pulmonary fibrosis.

Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital.

BACKGROUND: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. OBJECTIVES: To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. METHODS: This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged 75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. RESULTS: In cross-sectional analyses, elderly patients with pMAC disease had significantly lower role-physical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. CONCLUSIONS: Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

Use of PIXE/PIGE for sequential Ca and F measurements in root carious model.

The progress of caries has conventionally been evaluated by checking changes in mineral density using transverse microradiography (TMR). Recent advances have seen development of a new measurement system, using in-air micro proton induced X-ray/gamma-ray emission (PIXE/PIGE). PIXE/PIGE enables analysis of distributions and concentrations of multiple mineral elements in a carious lesion. The aim of this study was to evaluate the effectiveness of PIXE/PIGE for investigating the development of root caries. In summary, we successfully established a multi-elemental sequential measuring method using in-air micro-PIXE/PIGE to identify the dynamic distributions and concentrations of Ca and F in human root dentin. The PIXE/PIGE potentially offers a useful advantageous technique for studying carious development by using as a combination with conventional techniques such as TMR and Micro-computed tomography (µCT).

An innovative masticatory efficiency test using odour intensity in the mouth as a target marker: a feasibility study.

A large number of studies have reported the findings for masticatory efficiency tests; however, some objective masticatory efficiency tests have a drawback, in that subjects are required to spit out the test material. This study examined the possibility of a masticatory efficiency test that evaluates the intensity of odours released when chewing an odour compound-containing material. A total of 20 volunteers were used in this study. The odour intensity in the breath after chewing a gum was measured by portable odour sensor device. The odour intensity after chewing the gum was measured over four chewing durations and at four intervals between spitting out and measurement of the odour intensity. The volume of stimulated saliva was measured by calculating the difference in the weight of the gauze before and after chewing to examine the effect of saliva flow. With an increase in chewing duration, odour intensity reduced. The odour intensity was the highest immediately after chewing. There was a positive correlation between odour intensity and gummy jelly-related masticatory efficiency test value (G-METV), which was significant for 10-s chewing. The regression equation was calculated from three objective variables of odour intensity and G-METV as dependent variable. Pearson's correlation coefficient between G-METV and the odour intensity-related masticatory efficiency value (O-METV) was 0·68. The coefficient of variation of O-METV was significantly lower than that of G-METV. These results suggest that the masticatory performance can be estimated by measuring the odour intensity immediately after chewing food containing odour compounds for 10 s.

Early endoscopic management for early bowel obstruction after gastrectomy: a case report.

BACKGROUND: Early bowel obstruction is not a rare complication of gastrectomy, and it may require re-operation in some cases. CASE PRESENTATION: We report the case of a 71-year-old woman who underwent a total gastrectomy with Roux-en-Y reconstruction for a massive gastrointestinal stromal tumor. Postoperatively, she was making good progress and started consuming meals on postoperative day 3. However, on postoperative day 10, she complained of upper abdominal discomfort and nausea. Blood tests showed a mild inflammatory reaction. An upper gastrointestinal series showed obstruction of the elevated jejunum. An abdominal computed tomography scan suggested upper bowel obstruction. Endoscopic observation and repositioning was selected as an effective approach for treatment considering the patient's clinical condition and background. Upper gastrointestinal endoscopy showed kinking of the elevated jejunum, easy passage through to the anal intestine, and no evidence of mucosal edema, stenosis of the Roux-en-Y anastomosis, bowel ischemia, or necrosis. After endoscopic repositioning, upper gastrointestinal series showed good passage of the jejunum and no evidence of bowel obstruction. At the 6-month follow-up examination, the patient was in good condition and had no complaints. CONCLUSION: We concluded that early endoscopic management should be the effective procedure considered for diagnosis and treatment of early bowel obstruction after gastrectomy in some cases.

The timing of worm exclusion in dogs repeatedly infected with the cestode Echinococcus multilocularis.

Experimental Echinococcus multilocularis infection and deworming was repeated three or five times in nine dogs at various re-infection schedules. The mean number of worms decreased more than 91% in dogs with repeated infection, compared to first infection controls (n= 6). The copro-antigen assay and the egg count in the faeces suggested that the worm burden gradually decreased each time the dogs were re-infected. To examine whether such worm exclusion was a non-specific response, five dogs were sequentially infected with the parasite four times and subsequently fed freely for 6 months. Even after the 6-month interval, the five dogs that were infected five times with the parasite were still able largely to exclude the adult worms. The results suggested that the ability of worm exclusion in dogs that developed a resistance did not become rapidly extinct. Observation of the condition of faeces and the excretion of hooks in the faeces of repeatedly infected dogs revealed that the exclusion of worms started at the first week after the re-infection, and it continued during the patent period. Serum antibodies specific to the parasite antigen increased gradually until the third infection and significantly decreased during the 6-month interval. There was little enhancement of serum antibodies after the fifth infection in most dogs, although no clear correlation was observed between the antibody response and the worm burden. These findings suggested the possibility of developing a vaccine.

Optimised paediatric CT dose at a tertiary children's hospital in Japan: a 4-y single-centre analysis.

Since diagnostic reference levels (DRLs) for children are not currently established in Japan, the authors determined local DRLs for the full range of paediatric CT examinations in a single tertiary care children's hospital. A retrospective review of 4801 CT performance records for paediatric patients (<15 y old) who had undergone CT examinations from 2008 to 2011 was conducted. The most frequent examinations were of the head (52 %), followed by cardiac (15 %), temporal bone (9 %), abdomen (7 %), chest (6 %) and others (11 %). Approximately one-third of children received two or more CT scans. The authors' investigation showed that mean CTDIvol and DLP for head, chest and abdomen increased as a function of age. Benchmarking of the results showed that CTDIvol, DLP and effective dose for chest and abdomen examinations in this hospital were below average, whereas those for the head tended to be at or slightly above average of established DRL values from five countries. The results suggest that CT examinations as performed in a tertiary children's hospital in Japan are well optimised.

Short-term outcomes of robotic radical esophagectomy for esophageal cancer by a nontransthoracic approach compared with conventional transthoracic surgery.

Transthoracic esophagectomy (TTE) is believed to have advantages for mediastinal lymphadenectomy in the treatment of resectable esophageal cancer despite its association with a greater incidence of pulmonary complications and postoperative mortality. Transhiatal esophagectomy is regarded as less invasive, though insufficient in terms of lymph node dissection. With the aim of achieving lymph dissection equivalent to that of TTE, we have developed a nontransthoracic esophagectomy (NTTE) procedure combining a video-assisted cervical approach for the upper mediastinum and a robot-assisted transhiatal approach for the middle and lower mediastinum. We prospectively studied 22 accumulated cases of NTTE and verified feasibility by analyzing perioperative and histopathological outcomes. We compared this group's short-term outcomes with outcomes of 139 equivalent esophageal cancer cases operated on at our institution by conventional TTE (TTE group). In the NTTE group, there were no procedure-related events and no midway conversions to the conventional surgery; the mean operation time was longer (median, 524 vs. 428 minutes); estimated blood loss did not differ significantly between the two groups (median, 385 mL vs. 490 mL); in the NTTE group, the postoperative hospital stay was shorter (median, 18 days vs. 24 days). No postoperative pneumonia occurred in the NTTE group. The frequencies of other major postoperative complications did not differ significantly, nor were there differences in the numbers of harvested mediastinal lymph nodes (median, 30 vs. 29) or in other histopathology findings. NTTE offers a new radical procedure for resection of esophageal cancer combining a cervical video-assisted approach and a transhiatal robotic approach. Although further accumulation of surgical cases is needed to corroborate these results, NTTE promises better prevention of pulmonary complications in the management of esophageal cancer.

Effect of reducing dietary forage in lower starch diets on performance, ruminal characteristics, and nutrient digestibility in lactating Holstein cows.

This experiment evaluated the effect of feeding a lower starch diet (21% of dry matter) with different amounts of forage (52, 47, 43, and 39% of dry matter) on lactational performance, chewing activity, ruminal fermentation and turnover, microbial N yield, and total-tract nutrient digestibility. Dietary forage consisted of a mixture of corn and haycrop silages, and as dietary forage content was reduced, chopped wheat straw (0-10% of dry matter) was added in an effort to maintain chewing activity. Dietary concentrate was adjusted (corn meal, nonforage fiber sources, and protein sources) to maintain similar amounts of starch and other carbohydrate and protein fractions among the diets. Sixteen lactating Holstein cows were used in replicated 4×4 Latin squares with 21-d periods. Dry matter intake increased while physically effective neutral detergent fiber (peNDF1.18) intake was reduced as forage content decreased from 52 to 39%. However, reducing dietary forage did not influence milk yield or composition, although we observed changes in dry matter intake. Time spent chewing, eating, and ruminating (expressed as minutes per day or as minutes per kilogram of NDF intake) were not affected by reducing dietary forage. However, addition of chopped wheat straw to the diets resulted in greater time spent chewing and eating per kilogram of peNDF1.18 consumed. Reducing dietary forage from 52 to 39% did not affect ruminal pH, ruminal digesta volume and mass, ruminal pool size of NDF or starch, ruminal digesta mat consistency, or microbial N yield. Ruminal acetate-to-propionate ratio was reduced, ruminal turnover rates of NDF and starch were greater, and total-tract digestibility of fiber diminished as dietary forage content decreased. Reducing the dietary forage content from 52 to 39% of dry matter, while increasing wheat straw inclusion to maintain chewing and rumen function, resulted in similar milk yield and composition although feed intake increased. With the lower starch diets in this short-term study, the minimal forage content to maintain lactational performance was between 39 and 43%.

Elevated liver enzymes are related to progression to impaired glucose tolerance in Japanese men.

AIMS: To investigate whether the elevation of liver enzymes is associated with the progression from normal to impaired glucose tolerance. METHODS: A historical cohort study was conducted in 594 male workers at public schools, who had normal glucose tolerance at baseline. The progression to impaired glucose tolerance and impaired fasting glycaemia during a mean follow-up of 3.1 years was measured using an oral glucose tolerance test. RESULTS: Overall, 141 (23.7%) subjects developed impaired glucose tolerance and 68 (11.4%) subjects developed impaired fasting glycaemia, 23 of whom had combined impaired fasting glycaemia/impaired glucose tolerance. The incidence of impaired glucose tolerance increased significantly with increasing quartiles of serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase (P for trend <0.01). In Cox proportional hazards regression analysis, after adjusting for comprehensive risk factors, including plasma glucose levels, BMI and homeostatic model assessment of insulin resistance, the risk of progression to impaired glucose tolerance was significantly higher in the highest quartile of alanine aminotransferase than in the lowest quartile (hazard ratio 2.5; 95% CI 1.1-5.7). A significant association between alanine aminotransferase and the progression to impaired glucose tolerance was found after further adjustments for other liver enzymes or after the sample was limited to those with BMI < 25.0 kg/m(2) or with fasting plasma glucose < 5.5 mmol/l. CONCLUSIONS: A higher level of alanine aminotransferase was independently associated with progression from normal to impaired glucose tolerance in Japanese men. The elevation of alanine aminotransferase may be a change that occurs early in the evolution of diabetes.

Visualization and live imaging analysis of a mosquito saliva protein in host animal skin using a transgenic mosquito with a secreted luciferase reporter system.

Mosquitoes inject saliva into a vertebrate host during blood feeding. The analysis of mosquito saliva in host skin is important for the elucidation of the inflammatory responses to mosquito bites, the development of antithrombotic drugs, and the transmission-blocking of vector-borne diseases. We produced transgenic Anopheles stephensi mosquitoes expressing the secretory luciferase protein (MetLuc) fused to a saliva protein (AAPP) in the salivary glands. The transgene product (AAPP-MetLuc) of transgenic mosquitoes exhibited both luciferase activity as a MetLuc and binding activity to collagen as an AAPP. The detection of luminescence in the skin of mice bitten by transgenic mosquitoes showed that AAPP-MetLuc was injected into the skin as a component of saliva via blood feeding. AAPP-MetLuc remained at the mosquito bite site in host skin with luciferase activity for at least 4 h after blood feeding. AAPP was also suspected of remaining at the site of injury caused by the mosquito bite and blocking platelet aggregation by binding to collagen. These results demonstrated the establishment of visualization and time-lapse analysis of mosquito saliva in living vertebrate host skin. This technique may facilitate the analysis of mosquito saliva after its injection into host skin, and the development of new drugs and disease control strategies.

Hepatotoxicity of sub-nanosized platinum particles in mice.

Nano-sized materials are widely used in consumer products, medical devices and engineered pharmaceuticals. Advances in nanotechnology have resulted in materials smaller than the nanoscale, but the biologic safety of the sub-nanosized materials has not been fully assessed. In this study, we evaluated the toxic effects of sub-nanosized platinum particles (snPt) in the mouse liver. After intravenous administration of snPt (15 mg/kg body weight) into mice, histological analysis revealed acute hepatic injury, and biochemical analysis showed increased levels of serum markers of liver injury and inflammatory cytokines. In contrast, administration of nano-sized platinum particles did not produce these abnormalities. Furthermore, snPt induced cytotoxicity when directly applied to primary hepatocytes. These data suggest that snPt have the potential to induce hepatotoxicity. These findings provide useful information on the further development of sub-nanosized materials.

Reduction of malaria transmission by transgenic mosquitoes expressing an antisporozoite antibody in their salivary glands.

We have previously developed a robust salivary gland-specific expression system in transgenic Anopheles stephensi mosquitoes. To establish transgenic mosquito lines refractory to Plasmodium falciparum using this system, we generated a transgenic mosquito harbouring the gene encoding an anti-P. falciparum circumsporozoite protein (PfCSP) single-chain antibody (scFv) fused to DsRed in a secretory form (mDsRed-2A10 scFv). Fluorescence microscopy showed that the mDsRed-2A10 scFv was localized in the secretory cavities and ducts of the salivary glands in a secreted form. To evaluate P. falciparum transmission-blocking in a rodent malaria model, a transgenic Plasmodium berghei line expressing PfCSP in place of PbCSP (PfCSP/Pb) was constructed. The PfCSP/Pb parasites were able to bind to the mDsRed-2A10 scFv in the salivary glands of the transgenic mosquitoes. Importantly, the infectivity of the transgenic mosquitoes to mice was strongly impaired, indicating that the parasites had been inactivated. These results suggest that salivary gland-specific expression of antisporozoite molecules could be a promising strategy for blocking malaria transmission to humans.

Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis.

BACKGROUND: Molecular characterisation using gene-expression profiling will undoubtedly improve the prediction of treatment responses, and ultimately, the clinical outcome of cancer patients. METHODS: To establish the procedures to identify responders to FOLFOX therapy, 83 colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets. Using Random Forests (RF) algorithm in the training set, predictor genes for FOLFOX therapy were identified, which were applied to test samples and sensitivity, specificity, and out-of-bag classification accuracy were calculated. RESULTS: In the training set, 22 of 27 responders (81.4% sensitivity) and 23 of 27 non-responders (85.1% specificity) were correctly classified. To improve the prediction model, we removed the outliers determined by RF, and the model could correctly classify 21 of 23 responders (91.3%) and 22 of 23 non-responders (95.6%) in the training set, and 80.0% sensitivity and 92.8% specificity, with an accuracy of 69.2% in 29 independent test samples. CONCLUSION: Random Forests on gene-expression data for CRC patients was effectively able to stratify responders to FOLFOX therapy with high accuracy, and use of pharmacogenomics in anticancer therapy is the first step in planning personalised therapy.

Protective effects of mineralocorticoid receptor blockade against neuropathy in experimental diabetic rats.

AIMS: Mineralocorticoid receptor (MR) blockade is an effective treatment for hypertension and diabetic nephropathy. There are no data on the effects of MR blockade on diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether MRs are present in the peripheral nerves and to investigate the effectiveness of MR blockade on DPN in streptozotocin (STZ)-induced diabetic rats. METHODS: Expression of MR protein and messenger RNA (mRNA) was examined in the peripheral nerves using Western blot analysis and RT-PCR. We next studied the effects of the selective MR antagonist eplerenone and the angiotensin II receptor blocker candesartan on motor and sensory nerve conduction velocity (NCV), morphometric changes and cyclooxygenase-2 (COX-2) gene and NF-κB protein expression in the peripheral nerves of STZ-induced diabetic rats. RESULTS: Expression of MR protein and mRNA in peripheral nerves was equal to that in the kidney. Motor NCV was significantly improved by 8 weeks of treatment with either eplerenone (39.1 ± 1.2 m/s) or candesartan (46.4 ± 6.8 m/s) compared with control diabetic rats (33.7 ± 2.0 m/s) (p < 0.05). Sensory NCV was also improved by treatment with candesartan or eplerenone in diabetic rats. Eplerenone and candesartan caused significant improvement in mean myelin fibre area and mean myelin area compared with control diabetic rats (p < 0.05). COX-2 mRNA and NF-κB protein were significantly elevated in the peripheral nerves of diabetic rats compared with control rats, and treatment with eplerenone or candesartan reduced these changes in gene expression (p < 0.05). CONCLUSION: MR blockade may have neuroprotective effects on DPN.