Eight Thoroughbred horses were used to examine the effects of grass hay intake on the fiber digestion and the retention time of digesta in the total gastrointestinal tract and the hindgut segments. ...The horses were randomly assigned to 2 groups and offered 2.0 (high intake HI) or 1.3 kg DM/(100 kg BW • d; low intake LI) of timothy hay in equal amounts every 3 h for 17 d. The digestibility and total tract mean retention time of digesta (tMRT) in the total gastrointestinal tract were measured from d 11 to d 15. To measure the mean retention time of digesta in each hindgut segment (sMRT), the horses were euthanized on d 17, after being fed a series of hay markers that were labeled with different rare earth elements. The digesta were collected from the ileum, cecum, right ventral colon (RVC), left ventral colon (LVC), left dorsal colon, right dorsal colon (RDC), and small colon (SC) to measure fiber digestibility, sMRT, VFA concentration, and fibrolytic activities. The digestibility of NDF and ADF in the total gastrointestinal tract was lower (P < 0.01) for HI than for LI. The cumulative disappearance of NDF and ADF from the ileum to the LVC attained 90% of total tract digestion regardless of hay intake. Values did not differ according to treatments in the ileum and the cecum but were lower (P < 0.01) for HI than for LI in the postcecal segments. This was caused by the smaller increase in the cumulative NDF and ADF disappearance from the cecum to the RVC for HI than for LI. The solid phase tMRT was shorter (P = 0.04) for HI than for LI. Although sMRT in the RDC and SC were shorter (P = 0.04 and P < 0.01, respectively) for HI than for LI, no differences were observed in the other hindgut segments. There was no difference between treatments in the total VFA concentration, VFA proportions, or the specific activity of carboxymethyl cellulase and xylanase in each hindgut segment. The fibrolytic activity for the cecum and RVC were greatest and decreased beyond the LVC. A clear relation between mean retention time and fiber digestion was observed in the total gastrointestinal tract, but the segments where a difference in sMRT was detected because of the intake were not the same as those with the fiber digestibility depression. Although the reduction in total tract fiber digestibility with increased feed intake was clearly shown to occur between the cecum and RVC, which were the main segments for fiber digestion, it could be explained neither by the sMRT nor by the fibrolytic activity in these segments.
Objective The combination chemotherapy consisting of cisplatin and etoposide, one of the standard regimens for small cell lung cancer, has been widely used to treat extrapulmonary poorly ...differentiated neuroendocrine carcinomas. However, there were no prior reports limited to the hepatobiliary tract and pancreas as the primary sites. Methods We reviewed the cases in our database from October 1995 to January 2009 and retrospectively examined the clinical data of patients, with unresectable or recurrent poorly differentiated neuroendocrine carcinoma arising from the hepatobiliary tract and pancreas, who received combination chemotherapy with cisplatin and etoposide as the first-line treatment. The chemotherapy regimen consisted of cisplatin 80 mg/m2 given intravenously on day 1 and etoposide 100 mg/m2 intravenously on days 1–3, repeated every 3–4 weeks. Results Twenty-one patients were treated with the above regimen of cisplatin and etoposide combination chemotherapy. The primary tumor site was the liver in 2 patients, gallbladder in 8 patients, pancreas in 10 patients and ampulla of Vater in 1 patient. Although no complete responses were obtained, three patients had partial responses, resulting in an overall response rate of 14%. Median progression-free survival was 1.8 months, and median overall survival was 5.8 months. The major adverse events were myelosuppression and gastrointestinal toxicities, with Grade 3 or 4 neutropenia (90%), nausea (33%) and anorexia (24%). Conclusions Cisplatin and etoposide combination as the first-line chemotherapy for hepatobiliary or pancreatic poorly differentiated neuroendocrine carcinoma had only marginal antitumor activity and relatively severe toxicity compared with previous studies on extrapulmonary poorly differentiated neuroendocrine carcinoma treated with the same regimen.
SHP-2 protein tyrosine phosphatase plays an important role in activation of the RAS-dependent signaling. Gain-of-function mutations in the PTPN11 gene, which encodes SHP-2, have been found in the ...leukemia-prone developmental disorder Noonan syndrome as well as sporadic childhood leukemias, indicating that SHP-2 is a bona fide human oncoprotein. However, the role of SHP-2 mutations in non-hematological malignancies remains obscure. Here, we screened for PTPN11 mutations in primary solid tumors and identified a 1520C>A mutation that causes threonine-507 to lysine (T507K) substitution in the phosphatase domain of SHP-2 in a case of hepatocellular carcinoma. T507K SHP-2 exhibited altered substrate specificity with slightly elevated basal phosphatase activity. Upon expression in NIH3T3 cells, T507K SHP-2 induced transformed foci, which was not observed with wild type, Noonan-specific or leukemia-specific SHP-2. Furthermore, NIH3T3 cells transformed by T507K SHP-2 showed anchorage-independent growth and developed tumors in nude mice. These results indicate that quantitative and/or qualitative alteration in phosphatase activity determines the transforming potential as well as target cell/tissue spectrum of individual SHP-2 mutants as oncoproteins. Although rare in solid tumors, the identified T507K SHP-2 represents a distinct class of SHP-2 mutants with oncogenic RAS-like transforming activity, which could contribute to the development of solid tumors.
Oncolytic adenoviruses are a promising tool in cancer therapy. In this study, we characterized the role of autophagy in oncolytic adenovirus-induced therapeutic effects. OBP-405, an oncolytic ...adenovirus regulated by the human telomerase reverse transcriptase promoter (hTERT-Ad, OBP-301) with a tropism modification (RGD) exhibited a strong antitumor effect on glioblastoma cells. When autophagy was inhibited pharmacologically, the cytotoxicity of OBP-405 was attenuated. In addition, autophagy-deficient Atg5(-/-) mouse embryonic fibroblasts (MEFs) were less sensitive than wild-type MEFs to OBP-405. These findings indicate that OBP-405-induced autophagy is a cell killing effect. Moreover, autophagy-inducing therapies (temozolomide and rapamycin) synergistically sensitized tumor cells to OBP-405 by stimulating the autophagic pathway without altering OBP-405 replication. Mice harboring intracranial tumors treated with OBP-405 and temozolomide survived significantly longer than those treated with temozolomide alone, and mice treated with OBP-405 and the rapamycin analog RAD001 survived significantly longer than those treated with RAD001 alone. The observation that autophagy inducers increase OBP-405 antitumor activity suggests a novel strategy for treating patients with glioblastoma.
Summary
Background
Probiotic bacteria may be effective in the treatment of allergic inflammation and food allergy, but efficacy and underlying mechanisms remain unclear.
Objective
The present study ...investigated the effects of probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis (JCPsis).
Methods
In a randomized, double‐blind, placebo‐controlled trial, 44 JCPsis subjects received BB536 or placebo for 13 weeks during the pollen season. Subjective symptoms and self‐care measures were recorded daily and blood samples were taken before and during intervention to measure blood levels of parameters related to JCPsis.
Results
BB536 intake was associated with a significant reduction in number of subjects prematurely terminated due to severe symptoms and pollinosis medication (P=0.0057 vs. placebo group). Comparison of subjective symptom scores indicated significant decreases in rhinorrhea, nasal blockage and composite scores in the BB536 group compared with the placebo group. Comparison of medical scores showed marked improvements in all symptoms on BB536 intake. A T‐helper type 2 (Th2)‐skewed immune response occurring along with pollen dispersion was observed. BB536 significantly suppressed increases in plasma thymus‐ and activation‐regulated chemokine and tended to suppress elevations of Japanese cedar pollen (JCP)‐specific IgE.
Conclusion
These results suggest the efficacy of BB536 in relieving JCPsis symptoms, probably through the modulation of Th2‐skewed immune response.
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•Salt tolerant and sensitive cultivars of basil were characterized.•Photosystem functionality was better preserved in the tolerant cultivar.•The tolerant cultivar accumulated more Na+ ...in the leaf tissue.•The sensitive cultivar produced more ABA upon exposure to salt stress.
In this study, plant growth, water relations, ABA levels, ion accumulation patterns and chlorophyll fluorescence were functionally linked to salt stress tolerance of two basil cultivars (Napoletano and Genovese) with different stress sensitivity levels. Plants were treated with salty water at 0, 100 and 200mM of NaCl. Potential photosynthetic efficiency, non-photochemical quenching and upregulation of photodamage protection by D1 protein revealed higher salt tolerance in Genovese plants, which also resulted in improved water balance and photosynthesis preservation. Upon stress, these plants accumulated also lower ABA and were less affected than Napoletano by salinity in terms of biomass production. Genovese plants were able to upregulate the expression of genes for ROS scavenging and cation transport. These results along with the ability of GEN plants to accumulate larger amount of Na+ in the leaf tissue indicate that this cultivar was better suited to partially use Na+ as osmoticum.
The Challenge on Liver Ultrasound Tracking (CLUST) was held in conjunction with the MICCAI 2014 conference to enable direct comparison of tracking methods for this application. This paper reports the ...outcome of this challenge, including setup, methods, results and experiences. The database included 54 2D and 3D sequences of the liver of healthy volunteers and tumor patients under free breathing. Participants had to provide the tracking results of 90% of the data (test set) for pre-defined point-landmarks (healthy volunteers) or for tumor segmentations (patient data). In this paper we compare the best six methods which participated in the challenge. Quantitative evaluation was performed by the organizers with respect to manual annotations. Results of all methods showed a mean tracking error ranging between 1.4 mm and 2.1 mm for 2D points, and between 2.6 mm and 4.6 mm for 3D points. Fusing all automatic results by considering the median tracking results, improved the mean error to 1.2 mm (2D) and 2.5 mm (3D). For all methods, the performance is still not comparable to human inter-rater variability, with a mean tracking error of 0.5-0.6 mm (2D) and 1.2-1.8 mm (3D). The segmentation task was fulfilled only by one participant, resulting in a Dice coefficient ranging from 76.7% to 92.3%. The CLUST database continues to be available and the online leader-board will be updated as an ongoing challenge.
Microstructural development in chemically vapor-deposited (CVD) high-purity beta-SiC during neutron and self-ion irradiation at elevated temperatures was studied. The CVD SiC samples were examined by ...transmission electron microscopy following neutron irradiation to 4.5–7.7
×
10
25 n/m
2 (
E
>
0.1
MeV) at 300 and 800
°C and 5.1
MeV Si
2+ ion irradiation up to ∼200
dpa at 600–1400
°C. The evolution of various irradiation-produced defects including black spot defects, dislocation loops, network dislocations, and cavities was characterized as a function of irradiation temperature and fluence. It was demonstrated that the black spot defects and small dislocation loops continue to dominate at relatively low temperatures (<∼800
°C), whereas they grow into Frank faulted loops and finally develop into dislocation networks at a higher temperature (1400
°C). Substantial cavity formation on grain boundaries and stacking faults was confirmed after ion irradiation at 1400
°C. These observations were discussed in relation with the known irradiation phenomena in SiC, such as low temperature swelling and cavity swelling.
The effects of red- and blue-light irradiation at night on abscisic acid (ABA) synthesis and anthocyanin and sugar concentrations were examined in grape vines, which were grown in two different ...seasons. In grapes cultivated with early heating, the ABA concentrations were highest in blue-light-emitting diode (LED)-treated skin; however, those in grapes cultivated in the ordinary growing season were highest in red-LED-treated skin. The expressions of 9-cis-epoxycarotenoid dioxygenase (
VvNCED1
) and ABA 8′-hydroxylase (
VvCYP707A1
) were high in each treatment at veraison regardless of the growing season. In both seasons, anthocyanin concentrations were highest under the blue-LED treatment, followed by the red-LED treatment. The expressions of
VlMYBA1
-
2
,
VlMYBA2
, and
VvUFGT
coincided with anthocyanin concentrations. Sugar concentrations were increased by the blue-or red-LED treatment dependent on the growing season. The results suggest that blue- or red-LED irradiation at night may influence the ABA and anthocyanin metabolism including
VvNCED1
,
VlMYBA1
-
2
, and
VlMYBA2
and sugar synthesis in grape berries, although the degree of the effects differs with the growing season.
Aim
Precise biomarkers for predicting prognosis could help to identify high‐risk Crohn's disease (CD) patients to facilitate better follow‐up during the postoperative course. In this study, the ...primary aim is the identification of the most reliable nutrition marker that predicts surgical relapse in CD patients.
Method
We first evaluated the predictive value of various nutrition markers for postoperative surgical relapse in CD patients and identified the advanced lung cancer inflammation index (ALI) as a promising biomarker. Then, we assessed the clinical significance of preoperative ALI in CD patients using two cohorts.
Results
Preoperative ALI showed the highest correlation with reoperation rate compared with other nutritional parameters in CD patients receiving surgical resection (sensitivity 53%, specificity 86%, area under the curve 0.71). Lower levels of preoperative ALI were significantly correlated with the presence of perianal disease. A lower level of preoperative ALI was an independent prognostic factor for reoperation rate after an intestinal resection (hazard ratio 3.37, 95% CI 1.38–10.12, P = 0.006), and the prognostic impact of preoperative ALI was successfully validated in an independent cohort using the same cut‐off value.
Conclusion
Preoperative ALI might be useful for postoperative management of CD patients.
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