Pathogenicity of Anamorphic Fungi Plectosporium oratosquillae and Acremonium sp. to Mantis Shrimp Oratosquilla oratoria

The experiment was conducted to investigate the effects of oral administration of probiotic Halomonas sp. B12 (previously isolated from the intestine of Fenneropenaeus chinensis) on the intestinal microflora, immunological parameters, and midgut histological structure of F. chinensis. Shrimp (initial weight: 4.00 ± 0.10 g) were fed diets containing Halomonas sp. B12 at 0 (control), 3.68 × 107 (T1), and 7.18 × 1010 (T2) colony‐forming units per gram for 6 wk, respectively. The results showed that the total bacterial counts significantly increased (P < 0.05) with supplementation of dietary probiotic B12. However, Vibrio spp. counts significantly decreased (P < 0.05) in the intestine of shrimp with increasing dietary probiotic B12. Hemocyte counts in the shrimp fed the diets supplemented with probiotic B12 were significantly higher (P < 0.05) than the control group. Both phenoloxidase (PO) activity in plasma and hemocyte lysate supernatant were higher in the shrimp fed diets supplemented with probiotic B12 compared with the control group. No significant difference was found in PO activity in plasma between the T1 and the control (P > 0.05). PO activity in plasma was higher in T2 than that in T1. Cumulative shrimp mortality after 10‐d white spot syndrome virus (WSSV) challenge test significantly decreased with increasing dietary probiotic B12 (P < 0.05). No significant difference was found between T1 and control in cumulative shrimp mortality after challenge test (P > 0.05). The oral administration of probiotic B12 to F. chinensis was beneficial to protect the integrity of shrimp intestinal mucosal layer. In summary, even though the low dose (T1) had some effects on bacterial counts and immunological parameters, only the high dose (T2) significantly increased the resistance of the shrimp to WSSV.

This study was carried out to assess the pathogenicity of Plectosporium oratosquillae NJM 0662 and Acremonium sp. NJM 0672, both of which were isolated from mantis shrimp Oratosquilla oratoris, to kuruma prawn Penaeus japonicus by intramuscular injection of conidial suspensions. These fungi caused mortality in the injected kuruma prawn. The diseased kuruma prawn showed numerous black spots in the gills. Histopathologically, hyphae in the gill filaments and the injected sites were encapsulated by hemocytes. The results indicate that these two fungi are pathogenic against kuruma prawn.

Two fungal pathogens of the mantis shrimp (Oratosquilla oratoria) in Yamaguchi and Aichi Prefectures, Japan are described as the new species Plectosporium oratosquillae and Acremonium sp. (a member of the Emericellopsis marine clade). Both fungi infect the gills of the mantis shrimp, which become brown or black due to melanization. The former species is characterized by its slow growth on artificial seawater yeast extract peptone glucose (PYGS) agar, pale yellow to pale orange or grayish yellow colonies, short cylindrical solitary phialides with a wavy tip, and one-celled ellipsoidal conidia. Although lacking the two-celled conidia demonstrated by the type species Plectosporium tabacinum, the taxonomic placement of the new species was confirmed by DNA sequence analysis of the internal transcribed spacer (ITS) region of ribosomal DNA (ITS1, 5.8S rDNA and ITS2). Acremonium sp., the other causal pathogen, differs from P. oratosquillae by its fast growth on PYGS agar, pale orange to salmon-colored colonies, long, slender conidiophores consisting of solitary phialides with tips lacking an undulate outline, and typically cylindrical conidia. Analysis of ITS and beta-tubulin gene sequences placed this fungus within the phylogenetically distinct Emericellopsis (anam. Acremonium) marine clade. Various physiological characteristics of both pathogens were also investigated. This is the first report of a fungal infection found on the mantis shrimp in Japan.

An experimental study on the effects of ethanol and folic acid deficiency, alone or in combination, on pregnant Swiss mice

Editor – We would like to comment on an article published by Doi et al.1 The report was based on a review of studies examining the effectiveness of low and high administered doses of radioiodine for the ablation of thyroid remnant among patients with differentiated thyroid cancer. Their analysis was based on a previously published systematic review conducted by Hackshaw et al2 which concluded that there is currently insufficient evidence to reliably say whether a low dose is associated with a lower ablation success rate than a high dose. Doi et al, however, use the same studies to conclude that a low dose is worse, but there are fundamental problems with their analysis and interpretation. First, they combine studies with very different designs into a single meta-analysis producing a relative risk which appears to be precise and highly statistically significant. The relative risk of having a successful ablation in the low dose group compared to the high dose group was 0.73, 95% confidence interval (CI) 0.61–0.81. The 22 studies, on which this particular result is based, are a mixture of cohort studies, retrospective reviews of patient medical records, and randomized trials. It is inappropriate to combine these studies when the observational studies are likely to be affected by inherent biases and confounding, but the randomized trials are not. Indeed, meta-analyses of observational studies need to be interpreted with great care because the effect of potential confounding in each study could be magnified when the studies are combined, thus producing a spuriously precise effect.3 Sixteen of the 22 studies (73%) were observational, so their results will contribute most to the pooled result. The best evidence must come from randomized clinical trials. Second, when their analysis was restricted to the 6 randomized trials (in which no comparison was based on more than 150 patients in total), the pooled relative risk was 0.68 (95% CI 0.43–1.07), which was not statistically significant (P-value of 0.093). The correct interpretation is that, while there is some evidence of a lower ablation rate when using a low dose, the effect could be due to chance because the CI includes the no-effect value and P >0.05 (i.e., there could be no true difference). However, no comment was made on this. Third, the dose level that defines ‘low’ and ‘high’ differs greatly between these trials. For example, a low dose could be 30 or 50 mCi (a difference of two-thirds), and a high dose could be 50 or 100 mCi (a difference of two-fold). Because of this, it is best to not combine all the trials to produce a single relative risk. Once these considerations have been taken into account, there is no analysis that allows firm conclusions to be made about the comparison of low and high dose radioiodine in treating differentiated thyroid cancer. While some clinicians prefer to administer a high dose at present, it is misleading to rule out the use of a low dose based on current evidence. There are clear potential advantages, such as less time spent in isolation in hospitals and lower risk of future second malignancies.2 What is needed is a large randomized trial, and there are two such trials in progress in the UK and France, each based on several hundred patients.4 These trials will determine with sufficient certainty whether a low dose should be avoided, or could be used instead of a high dose.

Introduction: Clostridium difficile is implicated in 15%–25% of all cases of nosocomial antibiotic-associated diarrhea. Current guidelines recommend oral vancomycin 125 mg every six hours as the drug of choice for severe CDI. The recommendation is based on a retrospective analysis showing vancomycin to be superior to oral metronidazole for the treatment of severe disease, as well as data demonstrating no difference in outcomes between low (125 mg) and high (500 mg) dose vancomycin regimens. Despite this, many clinicians frequently prescribe higher doses (250, 500 mg) of oral vancomycin for severe CDI. While historical literature has suggested no benefit to increased doses of vancomycin, such data do not exist in the age of a more hypervirulent strain. Methods: This study evaluated adult patients admitted to four Detroit Medical Center hospitals hours with CDI confirmed by polymerase chain reaction and meeting severe CDI criteria. Patients received oral vancomycin 125mg every 6 hours (low dose), 250mg or 500mg every 6 hours (considered high dose for study purposes). Patients receiving concomitant CDI therapy were excluded. Exposure to concomitant antimicrobials was also collected. Groups were defined: low dose (LD) vs high dose (HD). P-values < 0.05 were considered significant. Results: From July 2010 to July 2012, this study included 137 CDI patients with a mean age of 67 years. LD group included 95 patients and HD group included 42. Baseline characteristics were similar between groups. Length of stay was 12 ± 9.6 LD v 11.8 ± 10.1 days HD, p=0.33. Duration of diarrhea was 4.2 days LD and 4.1 days HD, p=0.72. ICU admission was required in 28% LD patients and 26% HD, p=0.76. A mean of 2 non-CDI antimicrobials were received in 69% LD and 74% HD while on CDI therapy, p=0.61. Overall clinical cure was achieved in 74% LD and 67% HD, p=0.42. The overall mortality rate was not different between groups, 5.3% LD and 2.4% HD, p=0.67. Conclusions: Clostridium difficile is a very prevalent nosocomial infection. Many patients continue to receive concomitant antimicrobials while on CDI therapy. Increasing the dose of oral vancomycin for patients with severe CDI does not improve efficacy.

Japan's economy is entering a new phase of economic growth through the so-called “lost 15 years” since 1990. Particularly Tokyo and Aichi prefectures have been drawing attention as engine of new economic growth in Japan. Although the recovery of Japan's economy has resulted in an increase in the demand for traffic, construction of new roads in rural areas has been located in a serious situation. It is attributed to a decreasing trend in Japan's population and aging. Thus Japan's national budget will be being reduced in the future. On the other hand, the environmental issues that Japan is facing are becoming serious as well. Japan is one of countries which have ratified Kyoto Protocol, but attaining the target of Kyoto Protocol seems to be very difficult for Japan. Particularly the carbon dioxide emissions from the motor vehicles have still been showing an increasing trend. Thus one can observe a dilemma between the growing demand for traffic and the increasing environmental load in Japan. So this article aims at finding a solution for this dilemma developing an economy-transport-environment interactive model from the spatial point of view. In this study, Aichi, Shizuoka, and Nagano prefectures in Japan are taken as a study region, and then economy-transport-environment interactions are investigated focusing upon emissions of carbon dioxide, nitrogen oxide, sulfur oxide, and suspended particulate matter.JEL Classification: Q53, Q55, R41

There is growing evidence that docetaxel, a microtubule-targeting agent like the other taxane paclitaxel, induces dual cytotoxicity mechanism according to dose level. Postgenomics screening technologies are now more and more applied to the elucidation of drug response mechanisms. Proton nuclear magnetic resonance spectroscopy-based pharmacometabolomics was here applied to get further insight into the response of human MCF7 breast carcinoma cells to docetaxel at high (clinical, 5 microM) and low (1 nM) doses. The global response to both doses was evaluated by nuclear morphology and DNA content, the latter as an index of cell proliferation and DNA ploidy. High dose provoked long-lasting cell cycle arrest in mitosis during the first 48 h of exposure to treatment and severe decrease in DNA content followed by significant amount of cell death. In contrast, at low dose, no long-lasting cell cycle arrest was observed on micrographies, and DNA content was decreased but less than at high dose (P < 0.05), without significant cell death. This response was compared to biochemical alteration assessed by pharmacometabolomics. Thirty metabolites were identified and quantified. Metabolite profiling at clinical dose revealed time-dependent disorders in derivatives of glycolysis, lipid metabolism and glutathione metabolism. Comparison between high and low doses was performed at 72 h and showed common traits including the accumulation of cytidinediphosphocholine (x 5.0 and x 6.9, respectively, P < 0.03), the decrease in phosphatidylcholine (x 0.3 and x 0.2, respectively, P < 0.03), and gluthathione (x 0.6 and x 0.6, respectively, P < 0.03). Despite that, significant dose-dependent differences were found in 12 of 30 measured metabolites. Among them, the most discriminant metabolites were polyunsaturated fatty acids (ratio of high-to-low dose of 14.8, P < 0.05), glutamate, myoinositol, and homocysteine (ratio < 0.4, P < 0.05). In addition, the mechanism for glutathione decrease was different. At high dose, it resulted from extensive consumption with precursor starvation (glutamate: -89%, P < 0.05) and increased glutathione S-transferase activity (x 5, P < 0.01), whereas at low dose, it resulted from glutathione biosynthesis blockade with homocysteine accumulation (+144%, P < 0.03) and decreased glutathione S-transferase activity (-70%, P < 0.01). Altogether, this pharmacometabolomics analysis provides further evidence of the varying cellular responses at high and low doses of docetaxel in MCF7 breast cancer cells.

Comparison of low and high dose intracoronary adenosine and acetylcholine in women undergoing coronary reactivity testing: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

BackgroundWhile most of the clinical benefits of inhaled corticosteroid (ICS) therapy may occur at low doses, results of dose-ranging studies are inconsistent. Although symptom/lung function response to low and high dose ICS medication is comparable, it is uncertain whether low dose ICSs are as effective as high dose in the treatment of inflammation and remodeling.Methods22 mild or moderate asthmatic adult subjects (corticosteroid free for > 2 months) participated in a randomized, parallel group study to compare effects of fluticasone propionate (FP) 200 mcg/day and 1000 mcg/day. Alveolar macrophage (AM)-derived cytokines and basement membrane thickness (BMT) were measured at baseline and after 7 weeks treatment while symptoms, spirometry, exhaled nitric oxide (eNO) and airway hyperresponsiveness (AHR) to mannitol at baseline and 6 weeks.ResultsFP improved spirometry, eNO, symptoms and AHR with no difference between low and high dose FP. Both high and low dose FP reduced GM-CSF, TNF-alpha and IL-1ra, with no change in BMT and with no differences between low and high dose FP.Conclusions200 μg/day of FP was as effective as 1000 μg/day in improving asthma control, airway inflammation, lung function and AHR in adults in the short term. Future studies should examine potential differential effects between low and high dose combination therapy (ICS/long acting beta agonist) on inflammation and airway remodeling over longer treatment periods.

Morphological and biochemical adaptations to unilateral dopamine denervation of the neostriatum in newborn rats

A population of nearly 30,000 RFM and 11,000 BALB/c mice were exposed to graded radiation doses of ..gamma.. rays at a high (40 to 45 rad/min) or intermediate (8.3 rad/day) dose rate, or to fission neutrons at a high (5 to 25 rad/min) or low (1 rad/day) dose rate. Effects on life shortening are reported. The dose-response curve for ..gamma.. rays in RMF female mice at the high rate showed multiple changes in slope. In the region of 0 to 50 rad, the relationship between life shortening and dose could be described by a dose squared or a linear-dose-squared model with the dose-squared component predominating above approx. 4 rad. For RFM male mice after irradiation at the high dose rate, and for both RFM and BALB/c female mice irradiated at the intermediate dose rate, the curve was linear over the entire range of doses tested. Linear dose-response relationships were also observed with neutrons at both dose rates over the lower end of the dose range. The relative biological effectiveness of neutrons in the 0- to 50-rad range for RFM female mice irradiated at high dose rates was proportional to the -0.5 power of neutron dose, i.e., the RBE increased withmore » decreasing total dose. ..gamma.. rays were less effective in shortening life when delivered at an intermediate dose rate than at a high dose rate. With neutrons, the low dose rate was more effective than the high dose rate at high total doses for both strains. For the RFM, the low-dose rate neutron irradiation at low total doses was less effective than the high dose rate, while no dose-rate effect was observed for BALB/c mice in the low dose range.« less

In this study, four experimental assays were conducted to evaluate the use of a new silver nanoparticle formulation named Argovit-4, which was prepared with slight modifications to enhance its biological activity against white spot syndrome virus (WSSV) in shrimp culture. The goals of these assays were to (1) determine the protective effect of Argovit-4 against WSSV, (2) determine whether Argovit-4 supplemented in feed exhibits toxicity towards shrimp, (3) determine whether Argovit-4 as antiviral additive in feed can prevent or delay/reduce WSSV-induced shrimp mortality, and (4) determine whether Argovit-4 supplemented in feed alters the early stages of the shrimp immune response. In bioassay 1, several viral inocula calibrated at 7 SID50(shrimp infectious doses 50% endpoint) were exposed to 40, 100, 200 and 1,000 ng/SID50 of Ag+ and then intramuscularly injected into shrimp for 96 h. In bioassay 2, shrimp were fed Argovit-4 supplemented in feed at different concentrations (10, 100 and 1,000 µg per gram of feed) for 192 h. In bioassay 3, shrimp were treated with Argovit-4 supplemented in feed at different concentrations and then challenged against WSSV for 192 h. In bioassay 4, quantitative real-time RT-qPCR was performed to measure the transcriptional responses of five immune-relevant genes in haemocytes of experimental shrimp treated with Argovit-4 supplemented in feed at 0, 6, 12, 24 and 48 h. The intramuscularly injected Argovit-4 showed a dose-dependent effect (p < 0.05) on the cumulative shrimp mortality from 0–96 h post-infection. In the second bioassay, shrimp fed Argovit-4 supplemented in feed did not show signs of toxicity for the assayed doses over the 192-h experiment. The third and fourth bioassays showed that shrimp challenged with WSSV at 1,000 µg/g feed exhibited reduced mortality without altering the expression of some immune system-related genes according to the observed level of transcriptional. This study is the first show that the new Argovit-4 formulation has potential as an antiviral additive in feed against WSSV and demonstrates a practical therapeutic strategy to control WSSV and possibly other invertebrate pathogens in shrimp aquaculture.

Limb girdle muscular dystrophy (LGMD) 2A/R1, caused by mutations in the CAPN3 gene and CAPN3 loss of function, is known to play a role in disease pathogenicity. In this study, AAVrh74.tMCK.CAPN3 was delivered systemically to two different age groups of CAPN3 knockout (KO) mice; each group included two treatment cohorts receiving low (1.17 × 1014 vg/kg) and high (2.35 × 1014 vg/kg) doses of the vector and untreated controls. Treatment efficacy was tested 20 weeks after gene delivery using functional (treadmill), physiological (in vivo muscle contractility assay), and histopathological outcomes. AAV.CAPN3 gene therapy resulted in significant, robust improvements in functional outcomes and muscle physiology at low and high doses in both age groups. Histological analyses of skeletal muscle showed remodeling of muscle, a switch to fatigue-resistant oxidative fibers in females, and fiber size increases in both sexes. Safety studies revealed no organ tissue abnormalities; specifically, there was no histopathological evidence of cardiotoxicity. These results show that CAPN3 gene replacement therapy improved the phenotype in the CAPN3 KO mouse model at both doses independent of age at the time of vector administration. The improvements were supported by an absence of cardiotoxicity, showing the efficacy and safety of the AAV.CAPN3 vector as a potential gene therapy for LGMDR1.

Comparison of effects of no-, medium-, and high dose dexamethasone in adult cardiac surgery – A post-hoc analysis of the prospective, observational inflacor trial