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Supplementary Figures S2 and S3 - PDF file 2332K, Figure S2:SG3 tumors are positive for beta-catenin and Myf5 Figure S3:Normal development of Myf5 myoblasts in beta-catenin knockout mice

Supplementary Figure S9 - PDF file 867K,Figure S9: The SYT-SSX2 domain SSXRD executes �-catenin activation and myogenic differentiation

Supplementary Figure S1 - PDF file 554K, Breeding strategy used to generate beta-catenin-null SYT-SSX2 transgenic mice

Supplementary Figure S8 - PDF file 1084K, Figure S8: Effects of SSTC-104 on Wnt-regulated tissues

Supplementary Figures S4, S5, S6, S7 - PDF file 1832K, Figure S4:Pyrvinium effect on beta-catenin in SYT-SSX2 expressing C2C12 and synovial sarcoma cells Figure S5:Phosphorylated �-catenin and full-length APC in HS-SY-II and SYO-1 SS cells Figure S6:SSTC-104 effects on growth and beta-catenin in HS-SY-II synovial sarcoma cells Figure S7: LRP6 depletion in HS-SY-II synovial sarcoma cells induces �-catenin nuclear exit

Supplementary Figure S11 and Tables S1-S3 - PDF file 460K, Figure S11: Regulation of an embryonic Wnt-interactive network by SYT-SSX2 and in human synovial sarcomas Table S1: Differentially regulated Wnt components in mesenchymal precursor cells expressing SYT-SSX2 and in synovial sarcoma tumors Table S2: Differentially regulated Wnt targets in mesenchymal precursor cells expressing SYT-SSX2 and in synovial sarcoma tumors Table S3: The embryonic Wnt interactive network in mesenchymal precursor cells expressing SYTSSX2 and in synovial sarcoma tumors

Supplementary Figure S10 4882K, Figure S10a and S10b: Nuclear beta-catenin accumulation in human synovial sarcoma tumors

Supplementary Methods and Legends - PDF file 130K, Methods:Additional information on experimental techniques Legends: describing supplementary figures

This study was conducted to determine the effect of replacing fishmeal (FM) with fermented soybean meal (FSBM) for 12 weeks on the growth performance, feed utilization, immunological parameters, antioxidant enzymes assays and lipid peroxidation, digestive enzymes, and histopathological analysis of juvenile Litopeneaus vannamei (L. vannamei). By substituting 0.0%, 20%, 30%, and 40% FSBM for fishmeal (w/w), four isonitrogenous diets were generated. A total of 300 juvenile L. vannamei(1.59 ±0.01 g) were randomly allocated to the experimental fiber tanks at a rate of fifteen shrimp per tank, with three replicates for each treatment. Growth performance and feed utilization decline considerably (P < 0.05) with increasing amounts of FM replacement with FSBM in diets. In comparison to the juveniles fed the other experimental diets, the diet containing a moderate level of FM replacement (20% FSBM) considerably enhanced growth performance and feed consumption during the feeding trial. The 20% FSBM-fed group had the highest protein content. In contrast, raising FSBM levels significantly increased lipid content (P < 0.05) compared to the control. However, there were no statistically significant differences (P> 0.05) across FSBM treatments. Hemolymph plasma total protein (TP) concentration and lysozyme activity were substantially greater (P < 0.05) in 20% FSBM compared to 40% FSBM (P < 0.05). In addition, 20% FSBM exhibits a substantial (P < 0.05) increase in the activity of antioxidant enzymes (CAT SOD, GPX, and GR). In contrast, the control and 30% FSBM groups had considerably more lipid peroxidation marker (MDA) than the 20% and 40% FSBM groups. Hepatopancreas amylase activity was considerably elevated (P < 0.05) in the control group and with 40% FSBM. In addition, Hepatopancreas and intestinal protease and lipase activity increased significantly by 20% FSBM. Considerably more B-cells were present in the 40% FSBM diet than in the control diet, however they were significantly less prevalent in the 20% and 30% FSBM of diets (P < 0.05).

Nile tilapia(Oreochromis niloticus) fingerlings (average weight and length: 20.20 ± 0.20 g, 10 ±0.25 cm)cultivated at reusing water from systems with biofloc technology (BFT) under three treatments: T1: Control, T2: tilapia cultured in reused water biofloc (RW) with adding carbohydrate and T3: tilapia cultured in reused water biofloc (RW) without adding carbohydrate. Nine rectangular tanks (66 x 47 x 44 cm, 75L) were used with stocking densities (400 Fish/m3) for 60 days to investigate fish growth performance, feed utilization, body composition, survival, water quality and also economic evaluation was done. Fish were fed a commercial diet containing 30% crude protein. Growth performance of tilapia was recorded biweekly. Water temperature, dissolved oxygen and pH, were recorded daily, while NO2–, NO3–N; total hardness, carbonate hardness and total suspended solids were recorded biweekly. The body composition of the whole fish was determined at the end of the experiment. Results showed that the best water quality parameters, finial body weight, weight gain, daily weight gain, specific growth rate, final biomass, net yield, PER, FCR, FE, feed intake and economic evaluation were significantly(P 0.05). The present study recommended rearing Nile tilapia in reusing water from systems with biofloc technology (BFT) without adding carbon source for best growth performance and prolonged the useful life, quality of water and reduced overall water consumption.

Aim: This study was designed to evaluate immediate implant placement combined with sticky bone and enriched fibrin membrane for teeth exhibiting periapical pathosis clinically, radiographically and resonance frequency analysis. Subjects and methods: Thirteen immediate implant combined with sticky bone and CGF membrane were inserted in 13 patients suffering from teeth with periapical pathosis indicated for extraction. Preoperative cone beam CT (CBCT were taken for every patient to determine alveolar bone height, width and bone defects The change in the implant stability and bone density readings were measured using ostel device and (CBCT) immediatly, and after 6 months of healing. Results: the mean values of ISQ was 48, 02 1ry stability . After 6 months, the mean value was increased to 72. Increasing of ISQ was observed with the time with significant statistical difference in the value of ISQ in whole time of evaluation and There was statistically significant increase of bone density readings after 6 months. Conclusion: The Immediate implant placement combined with sticky bone and enriched fibrin membrane for teeth exhibiting periapical pathosis is a successful technique

The present study investigated the effect of rearing the meagre, Argyrosomus regius in brackish-water pond aquaculture without using supplementary feeding in the Mediterranean area near Damietta City during June, 2017 to June, 2018, Fingerlings of mean length 13.0cm and 40.0 g weight were stocked in brackish-water pond measuring 1 feddan and 1.25 m deep at a rate of 4000 fish/ feddan in a monoculture system on natural occurring prey (natural spawned tilapia) and small shrimp. Temperature varied from 21.0 – 30.8°C; pH, 7.4– 8.9; Dissolved Oxygen (DO), 4.0 – 5.0 mg /L and salinity, 16.0 – 18.8 ppt during the study. Meagre, attained average final length 40 cm/ fish and average final weight 1500g / fish at harvest with an increment of 1460.0g/ fish and a daily gain of 4.0g/ fish. Average survival rate was 80% and net production was 4640.0kg/ feddan. The results revealed that the cost of feeds accounted for the largest proportion (68.55%) of the total cost of fish production,then fingerlings (8.56%), rent (3.35%) and labor (12.60%). This is followed by cost of fixed input and variable coast (12%). This experiment demonstrated the possibility of cultivation of A. regius as well as the higher commercial value where better net return (54.48 LE /feddan) was recorded with investment return of 23.33 LE / return LE cost. The results of the study indicated meagre as a promising candidate for the brackish water pond aquaculture.

Chondrosarcoma is a group of primary bone cancers that arise from transformed cells of chondrocytic lineage. Tumor recurrence and metastasis are devastating for patients with chondrosarcoma since there are no effective treatment options. IDH mutations occur in over 50% of tumors from patients with conventional or dedifferentiated chondrosarcomas and represent an attractive target for therapy. However, their role in the pathogenesis of chondrosarcoma remains largely unknown. In this study, we sought to determine the association of IDH mutation and HIF-1

Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that ETV4 and ETV5 acted as drivers of synovial sarcoma growth, most likely through control of the cell cycle. Upon ETV4 and ETV5 knockdown, we observed a striking upregulation of DUX4 and its transcriptional targets that activate the zygotic genome and drive the atrophy program in facioscapulohumeral dystrophy patients. In addition to demonstrating the importance of inhibiting all three FGFRs, the current findings reveal potential nodes of attack for the cancer with the discovery of ETV4 and ETV5 as appropriate biomarkers and molecular targets, and activation of the embryonic DUX4 pathway as a promising approach to block synovial sarcoma tumors.

Stocking density is considered a priority topic in aquaculture research due to its bearing on the welfare of farmed fish and the need for future recommendations governing stocking density management on fish farms. The aim of this study was to evaluate the influence of stocking density (10, 20, 30 and 40 fry/L3) on growth performance, Feed utilization and survival rate of fry gilthead seabream (Sparus aurata). The results showed that the group of fry stocked at density 30 fry/ L3 was significantly the highest final weight, weight gain, daily gain, SGR and insignificant differences in survival rate. Growth performance parameters were the highest with stocking density 30 fry/ L3 compared with stocking density (10, 20 and 40 fry/ L3), respectively. The results indicated that the best FCR, PER and FE group of fry stocked at 30 fry/ L3 than the rest of experimental groups. Stocking density also did not affect the crude protein and moisture content in body composition. But ash content was significantly highest at density 30 fry/ L3 than the rest of other stocking density (10. 20 and 40 fry/L3) groups. In contrast, total lipid was significantly highest at density 10 fry/L3 than the rest of experimental groups (20, 30 and 40 fry/L3). From the aforementioned results, it could be concluded that stocking density 30 fry/L3 had the best growth performance and feed utilization under experimental conditions.

Astudy was undertaken to determine the effect of the dietary lipid levels on growth performance , feed utilization and body composition of Nile tilapia larvae. Four isonitrogenous diets (40% crude protein) and dietary lipid levels (4, 6, 8 and 10% DM) were fed to satiation Nile tilapia larvae for 9 weeks. The best survival, weight gain, specific growth rate (SGR), protein efficiency ratio (PER), feed conversion ratio (FCR) and feed efficiency were observed for larvae fed 8% lipid level. While the poorest survival, specific growth rate (SGR), protein efficiency ratio (PER), lowest weight gain, specific growth rate (SGR), feed efficiency and highest feed conversion ratio (FCR), were observed with larvae fed 4% lipid level. The lipid content of fish were positively correlated with dietary lipid level. The body protein content increased with increasing the protein levels in the diet. It could be concluded that the requirement of lipid for Nile tilapia fry was 8% lipid under the present experimental condition.

The present study was performed to investigate the influence of feeding diets contained three levels of yellow corn (YC) without or with enzymes and/or prebiotics on the nutrient digestibility and blood parameters of growing New Zealand White (NZW ) rabbits. A feeding trial (3x4) with factorial arrangement of treatment was carried out. The chemical analyses for experimental diets and faces and blood constituents were run. One hundred and eight, 6 weeks old weaning NZW rabbits were used in this study. Rabbits were randomly distributed into 12 equal experimental groups; each contained three equal replicates. The digestibility coefficients of dry matter (DM), organic matter (OM), crude fiber (CF), ether extract (EE), nitrogen free extract (NFE), non-ditrgant fiber (NDF), ADF and hemicellulose were increased with feeding on 15 % YC diets than those of rabbits fed on 5 % or 10 % YC rations, but there was no significant effect of dietary treatments on DMI and CP digestibility. Rabbits fed enzyme-supplemented diets displayed significantly lower DM, OM, CF, EE, NFE, NDF, ADF and hemicellulose than those of other dietary treatments. There was no significant effect of these supplements on DMI (g/d) and CP digestibility, compared with the control diet (without supplements). The digestible DCP (%), TDN% and DEI (kcal/d) were significantly higher (P≤0.05) for animals fed diets containing 15 % YC than feeding on 5 or 10 % YC diets, while there were no significant effect on TDNI (g/d), CPI (g/d) and DEI (kcal/d). Rabbits fed the enzyme-supplemented diets exhibited significantly lower TDN (%) and DE (kcal/kg) than did those fed other experimental diets. Similarly, significantly lower means of DEI (kcal/d) were recorded by rabbits fed enzyme- or enzyme plus prebiotics-supplemented diets compared with other experimental groups of rabbits, but DCP % and CPI (g/d) were not affected. The plasma levels of triglycerides and total cholesterol were significantly lower for rabbits fed diets with 10 % or 15 % YC than those of rabbits fed the lowest level of YC,, while there was no significant effect on ALT, AST, total protein or urea concentration. Rabbits fed the diets fortified with enzymes plus prebiotics exhibited significantly lower (P≤0.05) levels of plasma urea and triglycerides and significantly higher cholesterol concentration than did the control group. In conclusion, using YC to partially replace wheat bran in growing rabbits diets had no negative effect on the nutritive value of diets. The nutritive value of the experimental diets for growing rabbits could increase by supplementing enzymes plus prebiotics. The present study showed that feeding growing rabbits on diets contained 10 % YC without supplements or feeding on diets contained 15 % YC with enzymes and prebiotics are effective for nutrient digestibility, nutritive value and health status of rabbits.

Extensive use of fertilizers and pesticides led to dangerous ecological effects and therefore the biological approaches have been widely recommended to prevent further deterioration for the environment. The current study was conducted to explore the potentiality of using single or combined inoculations by mycorrhizae, Bacillus subtilis and Pseudomonas fluorescence for controlling the infection of common bean plants with Sclerotium rolfsii on one hand and as bio-fertilizers for improving plants nutritional status on the other hand. The soil of study was mildly infected with S. rolfsii and contained high total-P content. Thus, minimal P inputs were added to the inoculated soil in the form of rock phosphate. Activities of plant defense enzymes i.e. chitinase, peroxidase and polyphenol oxidase were determined under the greenhouse conditions and the results obtained herein indicated that activities of such enzymes increased significantly owing to bio-agent inoculations. In this concern, combined treatments resulted in further significant increases over the single ones. A field study was then conducted for two successive years and the results reveal that single inoculations increased straw and green pod yields as well as the uptake of P and Fe by plants as compared with the non-inoculated treatment. Combined inoculants recorded further significant increases in these parameters even when compared with the fungicide treated plants. Generally, straw and pod yields obtained from the second growing season were significantly higher than those attained in the first growing one. Our study confirms the success of the used bio-treatments in minimizing soil pollution through fertilizer and/or pesticide inputs.

The ACC/AHA Pooled Cohort Equations (PCE) Risk Calculator is widely used in the US for primary prevention of atherosclerotic cardiovascular disease (ASCVD), but may under- or over-estimate risk in some populations. We therefore designed an automated, population-specific ASCVD risk calculator using machine-learning (ML) methods and electronic medical record (EMR) data, and compared its predictive power with that of the PCE calculator.We collected data from 101,110 unique EMRs of living patients from January 1, 2009 to April 30, 2020. ML techniques were applied to patient datasets that included either only cross-sectional (CS) features, or CS combined with longitudinal (LT) features derived from vital statistics and laboratory values. We compared the utility of the models using a proposed new cost measure (Screened Cases Percentage @ Sensitivity level). All ML models tested achieved better predictive power than the PCE risk calculator. The random forest ML technique (RF) applied on the combination of CS and LT features (RF-LTC) produced the best area under curve (AUC) score of 0.902 (95% confidence interval (CI), 0.895-0.910). To detect 90% of all positive ASCVD cases, the best ML model required screening only 43% of patients, while the PCE risk calculator required screening 69% of patients.Prediction models built using ML techniques improved ASCVD prediction and reduced the number of screenings required to predict ASCVD when compared with the PCE calculator, alone. Combining LT and CS features in the ML models significantly improved ASCVD prediction compared with using CS features, alone.

Context Familial hypercholesterolemia (FH) confers a greatly increased risk for premature cardiovascular disease, but remains very underdiagnosed and undertreated in primary care populations. Objective We assessed whether using a hybrid model consisting of 2 existing FH diagnostic criteria coupled with electronic medical record (EMR) data would accurately identify patients with FH in a Midwest US metropolitan healthcare system. Methods We conducted a retrospective, records-based, cross-sectional study using datasets from unique EMRs of living patients. Using Structured Query Language to identify components of 2 currently approved FH diagnostic criteria, we created a hybrid model to identify individuals with FH. Results Of 264 264 records analyzed, between 794 and 1571 patients were identified as having FH based on the hybrid diagnostic model, with a prevalence of 1:300 to 1:160. These patients had a higher prevalence of premature coronary artery disease (CAD) (38-58%) than the general population (1.8%) and higher than those having a high CAD risk but no FH (10%). Although most patients were receiving lipid-lowering therapies (LLTs), only 50% were receiving guideline-recommended high-intensity LLT. Conclusion Using the hybrid model, we identified FH with a higher clinical and genetic detection rate than using standard diagnostic criteria individually. Statin and other LLT use were suboptimal and below guideline recommendations. Because FH underdiagnosis and undertreatment are due partially to the challenges of implementing existing diagnostic criteria in a primary care setting, this hybrid model potentially can improve FH diagnosis and subsequent early access to appropriate treatment.

To determine the outcomes of Ahmed glaucoma valve (AGV) and transscleral diode cyclophotocoagulation (CPC) in neovascular glaucoma (NVG).This was a single-center retrospective comparative case series involving chart review of consecutive patients who underwent AGV or CPC for treatment of NVG and had ≥6 months of follow-up. Surgical failure at 6 months, defined as an IOP of21 or6 mm Hg with hypotony maculopathy after 1 month, progression to no light perception (NLP) vision, glaucoma reoperation, or removal of AGV were the main outcome measures.In total, 121 eyes of 121 patients were included (70 AGV and 51 CPC). Baseline demographics, visual acuity (VA), and intraocular pressure (IOP) were comparable between groups. At 6 months, failure was significantly higher in the CPC group than in the AGV group (43.1% vs. 17.1%, P = 0.020). Both groups had similar IOP and medication number at 6 months, but VA was significantly lower in the CPC group compared to the AGV group (2.4 ± 0.8 vs. 1.9 ± 1.0, P = 0.017). More CPC eyes required reoperation for glaucoma than AGV eyes (11.8% vs. 1.4%, P = 0.041). Multivariate regression analysis identified higher preoperative IOP (P = 0.001) and CPC surgery (P = 0.004) as independent predictors of surgical failure at 6 months. Age, sex, race, NVG etiology, bilaterality of the underlying retinal pathology, perioperative retina treatment, and prior or combined vitrectomy were not significant.AGV and CPC had comparable IOP and medication reduction in NVG eyes at 6 months. CPC was more frequently associated with failure, reoperation for glaucoma, and worse visual outcomes. High preoperative IOP and CPC surgery independently predicted surgical failure.

Pieris rapae L. is one of the most economically important pests of Brassicaceae causing extensive defoliation of plants. Entomopathogenic fungi and nematodes are promising biological control agents. The virulence of each of them tested alone against 4th instar larvae and pupa of P. rapae. The entomopathogenic fungi, Beauveria bassiana showed efficiency against 4th instar larvae and pupae with LC50: 28.857x103 and 175.406x103 spore/ml, respectively. Also, the entomopathogenic nematode, Steinernema carpocapsae was revealed efficacy against 4th instar larvae and pupae with LC50: 18.148 and 38.96 IJs/larva and pupa, respectively. In addition, the interaction of S. carpocapsae with Beauveria bassiana against P. rapae larvae was studied. An antagonistic effect was clearly seen when S. carpocapsae nematode was applied immediately after the B. bassiana. However, the synergistic or the additive effect was seen when the application of the EPNs 12h after their treatment with B. bassiana.

The present study was carried out to study the possibility of early weaning of gilthead sea bream (Sparus aurata) larvae. Therefore seabream larvae divided into different groups and weaned at 35, 40, 45, 50, 55and 60 days post hatching (dph). At the end of the experiment the mean wet weight and length of gilthead seabream were recorded for larvae. Showed that, the late weaning (50, 55 or 60 dph) significantly increased the wet weight and length of larvae compared to larvae groups that early weaned (35 and 40 dph) and the same trend was also observed for larvae after 60 dph. During the entire experimental period the highest SGR values were recorded for groups 60 and 55 dph (3.75 and 3.19), while the lowest SGR recorded for group 35 dph (1.59) indicating that, the late weaning age released the best SGR was compared to the early weaning of gilthead seabream larvae . The obtained results indicated that the late weaning of larvae (60 dph) significantly increased each of protein and fat content of larvae when compared to the early weaning of larvae (35 dph). In conclusion, it can be concluded that, the early weaning could not only improve the growth performance, but also keep the survival rate within the same limits for the original late weaning age.

One hundred and eight, 6 weeks of age weaning New Zealand White (NZW) rabbits were used in this study to investigate the impact of feeding three levels of yellow corn diets without or with enzymes or prebiotics or both. Rabbits were distributed in a completely randomized experimental design in a 3×4 factorial arrangements, with the variables being supplementation or not with enzymes (500 g / ton feed) or prebiotics (500 g / ton feed) or both (500 g enzymes +500 g prebiotics) / ton feed. The experimental groups of rabbits were fed their respective experimental rations in pelleted form. Three basal rations were used in this study; the first containing 5% corn (R1), the second one contained 10% corn (R5) and the third one contained 15% corn (R9). The composition and calculated analysis of the basal diets were done according to NRC (1977). The basal ration (R1) was supplemented with enzymes or prebiotics or both for R2, R3 and R4, respectively. While the basal ration (R5) was supplemented with enzymes or prebiotics or both for R6, R7 and R8, respectively, and the basal ration (R9) was supplemented with enzymes or prebiotics or both for R10, R11 and R12, respectively. Apart from the effect of feed rations which were contained 5% or 15% corn, were significantly (P 0.05) on live body weight of rabbits at different ages of the experimental period, from 6 to 15 weeks of age. Apart from the effect of corn levels and dietary supplements had no significant effect (P< 0.05) on daily feed intake (DFI) of rabbits during the period from 6 to 15 weeks. The daily feed intake (DFI) of rabbits fed rations contained 5%, 10% and 15% corn were 89.88, 89.03 and 89.62 g / d, respectively. The interaction between dietary corn levels and added supplements on feed conversion ratio (FCR) duringthe whole experimental period (from 6-15 weeks) showed that, the FCR of the growing rabbits were better(P

The effect of dietary protein levels (35%, 40% and 45%) on growth, survival, feed utilization and body composition of mono sex and mixed sex of Nile tilapia; Oreochromis niloticus L. fry was investigated. Fish were fed frequently to satiation for 7 days a week for 56 days. Results showed that fish growth was significantly affected by protein level. The highest growth performance of fry were obtained with 45% protein diet and the poorest one was obtained with 35% protein diet in both mono and mixed sex Nile tilapia, Oreochromis niloticus fry. Mono sex tilapia were reared in hap in earthen pond showed the highest weight gain, specific growth rate, feed conversion ratio, feed efficiency and protein efficiency ratio, while mixed-sex tilapia showed the lowest weight gain, specific growth rate, feed conversion ratio, feed efficiency and protein efficiency ratio. In conclusion, it was found that 45% crude protein had the highest growth performance parameters, feed utilization and economical evaluation for mono sex Nile tilapia (O. niloticus) fry under this experimental condition.

Objective:Postoperative renal dysfunction necessitating hemodialysis after implantation of ventricular assist devices presents a challenge with respect to establishment of hemodialysis access. Lack of pulsatile flow has led to concerns that arteriovenous fistulas will not mature. This study aims to evaluate arteriovenous fistula as a method of hemodialysis.Methods:Consecutive patients who underwent implantation of a ventricular assist device between 1988 and 2016 with a subsequent need for hemodialysis were identified. Retrospective data were collected for patients requiring hemodialysis through an arteriovenous fistula or arteriovenous graft. Access flow rates and duration of patency are reported.Results:Sixty-four patients were identified (10 required long-term hemodialysis, 5 via arteriovenous fistula, 1 via arteriovenous graft). All six patients receiving long-term hemodialysis access were on continuous-flow ventricular assist devices. Brachiocephalic arteriovenous fistulas were performed in all arteriovenous fistula patients, and the average preoperative vein diameter was 4.1 ± 0.9 mm. On 30-day follow-up, the average flow rate was 1262 ± 643 mL/min (880–2220). In arteriovenous fistula patients, one died at 30 days, one arteriovenous fistula required ligation for steal syndrome at 5 months, and one was abandoned after 10.7 months for low flow. Of remaining fistulas, one was converted to an arteriovenous graft at 1.7 years for malfunction (with 5.3 month patency), and one remains open at 4.0 years.Conclusion:Arteriovenous fistulas should be considered in selected patients with ventricular assist devices as a means of long-term hemodialysis access to avoid use of catheters. Maturation and usage of primary arteriovenous fistulas is possible despite lack of pulsatile flow.

Sclerotium rolfsii is a soil-borne fungus that causes big losses in productivity of various plant species including Phaseolus vulgaris L. The objectives of this study were to (1) evaluate the impacts of Sclerotium rolfsii on growth and production of common bean plants, (2) determine the effects of Sclerotium rolfsii on nutritive contents of beans, and (3) test the efficacy of bio-inoculants on suppressing plant infection with Sclerotium rolfsii. To fulfill these objectives, we used a coupled pot and field experimental approaches during two growing seasons. Common beans were inoculated with either arbuscular mycorrhizal fungi (Claroideoglomus etunicatum), Saccharomyces cerevisiae, or Trichoderma viride solely or in different combinations. Non-inoculated plants and fungicide treated ones were considered as reference treatments. Throughout these experiments, minimal amounts of rock phosphate were added during soil preparation for bio-inoculated treatments, while the non-inoculated reference treatments received a full dose of P as calcium superphosphate. Results revealed that all tested bioinoculants significantly raised the activities of plant defense enzymes i.e. chitinase, peroxidase and polyphenoloxidase as compared to non-inoculated control. Likewise, pre-, post- and plant survival percentages significantly increased due to these bio-inoculations. Increased survival percentages were attributed to the concurrent increases in uptake of N, P and Zn nutrients by plants treated with bioinoculants. In this concern, plant nutrients uptake was higher in combined than single bio-inoculant treatments. Moreover, the uptake values of plant nutrients owing to the combined bio-inoculants were higher than the corresponding ones achieved due to fungicide treatment. In conclusion, application of the tested bio-inoculants, especially the combined ones can be considered an eco-friendly approach that not only enhances plants resistance against infection with Sclerotium rolfsii but also improves plant nutritive status.

Objectives: To evaluate the prevalence of occult hepatitis B viral infections (OBIs) among blood donors considering the clinical and epidemiological importance of identifying OBIs. Methods: A cross-sectional study conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between January 2011 and January 2012. Blood donors (n=8501) were screened for Hepatitis B virus surface antigen (HBsAg) and hepatitis B core antibodies (HBcAb). All HBsAg-negative and HBcAb-positive samples were tested further for hepatitis B surface antibodies (HBsAb), hepatitis B virus (HBV)-DNA, and HBV genotyping. Results: Of the 8501 serum samples tested, 56 (0.7%) were positive and 8445 (99.3%) were negative for HBsAg. Among the HBsAg-negative samples, 198 (2.3%) were positive for HBcAb and these patients were suspected to have OBIs. Among the HBcAb-positive samples, 119 (60.1%) were positive while 79 (39.9%) were negative for HBsAb. Analysis of HBV-DNA for the suspected OBIs showed that 17 out of 198 samples (8.6%) yielded positive results, and all of them were HBsAb-negative. The viral load was low (less than 20-186 IU/mL) in all OBIs. Hepatitis B virus genotyping showed that 15 out of 17 samples (88.2%) were genotype D, and the other 2 samples (11.8%) were genotype E. Conclusion: The prevalence of OBIs among blood donors in Riyadh was 0.2%. Therefore, it is recommended that HBV molecular testing should be incorporated with serological assays for screening of blood donors. Saudi Med J 2016; Vol. 37 (10): 1114-1119 doi: 10.15537/smj.2016.10.14708 How to cite this article: Alshayea AI, Eid GE, El-Hazmi MM, Alhetheel AF. Prevalence and characterization of occult hepatitis B infection among blood donors in central Saudi Arabia. Saudi Med J . 2016 Oct;37(10):1114-9. doi: 10.15537/smj.2016.10.14708.

Chondrosarcomas are a heterogeneous group of malignant bone tumors that produce hyaline cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers, including conventional and dedifferentiated chondrosarcomas. These mutations lead to the inability of IDH to convert isocitrate into &alpha, ketoglutarate (&alpha, KG). Instead, &alpha, KG is reduced into D-2-hydroxyglutarate (D-2HG), an oncometabolite. IDH mutations and D-2HG are thought to contribute to tumorigenesis due to the role of D-2HG as a competitive inhibitor of &alpha, KG-dependent dioxygenases. However, the function of IDH mutations in chondrosarcomas has not been clearly defined. In this study, we knocked out mutant IDH1 (IDH1mut) in two chondrosarcoma cell lines using the CRISPR/Cas9 system. We observed that D-2HG production, anchorage-independent growth, and cell migration were significantly suppressed in the IDH1mut knockout cells. Loss of IDH1mut also led to a marked attenuation of chondrosarcoma formation and D-2HG production in a xenograft model. In addition, RNA-Seq analysis of IDH1mut knockout cells revealed downregulation of several integrin genes, including those of integrin alpha 5 (ITGA5) and integrin beta 5 (ITGB5). We further demonstrated that deregulation of integrin-mediated processes contributed to the tumorigenicity of IDH1-mutant chondrosarcoma cells. Our findings showed that IDH1mut knockout abrogates chondrosarcoma genesis through modulation of integrins. This suggests that integrin molecules are appealing candidates for combinatorial regimens with IDH1mut inhibitors for chondrosarcomas that harbor this mutation.

The objective of this study was to apply a biological control program on cucumber crop under greenhouse conditions, using biological control agents compared with insecticides to control the cotton aphid, Aphis gossypii Glover. The treatments were conducted at Dokki, Giza, Egypt, through two cucumber summer plantations in 2015 and 2016. Inspection was made once a week to determine the population density of A. gossypii, one of the major pests on cucumber. Aphid infestation occurred from week 6 to week 12 in 2015 and from week 4 to week 11 in 2016. Adults of the aphid parasitoid Aphidius colemani Viereck and larvae of the predatory coccinellid, Coccinella septempunctata L., were released in the biological greenhouse in weeks 8, 9, and 10 in season 2015 and 7, 8, and 9 in season 2016. In the insecticide greenhouse, the recommended insecticide program was used. The cost of control in the biological control greenhouses was more than that in the insecticide one, but the yield was much higher, recording 63.88% increase in 2015 and 64.91% in 2016.

The purpose of this study was to test the ability of some essential oils to dissolve three types of commercial gutta-percha brands which are commonly used in Egypt. The chemical composition of three commercially available gutta-percha brands (Hygenic, Maillefer and Meta) was determined using X-ray, FTIR and elemental microanalysis. Essential oils from thirty medicinal plants representing the six most famous families of aromatic plants growing in Egypt were extracted by steam distillation and tested for dissolving the gutta-percha brands. Essential oils from the peels of Citrus x sinensis (L.) Osbeck (Navel orange), C. deliciosa Tenora (Common mandarin) and C. x aurantium L.(Bitter orange)(Rutaceae) showed the highest dissolution rate. The essential oils from the aerial parts of Origanum syriacum L. and Lavandula hyprida Reverchon cv. Grosso (Labiateae) showed complete dissolution at 40oC, also essential oils from the seeds of Elletaria cardamomum (Cardamom) Matonvar. miniscula Burkill (Zingibracea...

Introduction Considering the large number of patients undergoing anterior cruciate ligament (ACL) surgery, it is important for radiologists to be familiar with these procedures, the normal imaging findings as well as the appearances of common complications that can occur in these patients. Symptomatic patients might present with complications related to the graft itself or due to other causes not related to the graft. Aim of the work Evaluate the MRI findings in symptomatic patients following ACL surgery. Patients and methods The study included 26 symptomatic patients following anterior cruciate ligament surgery. The examination was done on 1.5 Tesla magnet MRI machines. Results Twenty-five patients had reconstruction surgery (96%) and 1 patient had fixation of tibial attachment (4%). Among 25 cases of ACL reconstruction 21 patients had semi-membranosus/semi-tendinosus graft (84%) and 4 patients had Bone-patellar tendon-Bone graft (16%). The most common finding was complete graft tear (32%); followed by abnormal tunnel position (24%); screw failure (16%); graft impingement and partial graft tear (12% each); tibial tunnel and femoral tunnel cysts (8% each); arthrofibrosis (4%). Conclusions MRI is the modality of choice in evaluating the causes of symptomatic patients following ACL reconstruction surgery.

Cellular metabolism reprogramming is an emerging hallmark of cancer, which provides tumor cells with not only necessary energy but also crucial materials to support growth. Exploiting the unique features of cancer metabolism is promising in cancer therapies. The growing interest in this field has led to numerous inhibitors being developed against key molecules in metabolic pathways, though most of them are still in preclinical development. Potential targeted cancer cell metabolic pathways under investigation include glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), glutaminolysis, pentose phosphate pathway (PPP), lipid synthesis, amino acid and nucleotide metabolism. Sarcoma is a type of cancer that arises from transformed cells of mesenchymal origin, in contrast to carcinoma which originates from epithelial cells. Compared with carcinoma, progress towards harnessing the therapeutic potential of targeting sarcoma cell metabolism has been relatively slow. Recently however, with the discovery of cancer-specific mutations in metabolic enzymes such as isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH) in certain sarcoma types, cancer cellular metabolism has been considered more as a source of new targets for treating sarcoma. In this article, we review metabolic enzymes currently tested for cancer therapies and describe the therapeutic potential of targeting IDH mutations and SDH deficiency in sarcomas.

In this experiment, fifty four, 6-week-old weaned New Zealand White rabbits were used to investigate the impact of dietary supplementation with nano-selenium or glutamine on growth performance and carcass characteristics of growing rabbits fed diets containing two crude protein levels. A factorial experiment (2x3), being two levels of dietary crude protein (16 and 14 %) without or with organic nano-Se (0.1 mg/kg feed) and glutamine (10 g/kg feed) were performed. Rabbits were randomly distributed into 6 equal experimental groups; each contained three equal replications. Each replicate group was housed in a separate cage and fed their respective experimental diets from 6 to 15 weeks of age. Feed and water were offered ad libitum throughout the experimental period. Apart from the effect of feed supplements, rabbits fed the normal crude protein level (16%) achieved significantly better growth performance (final live body weight, daily weight gain, daily feed intake and feed conversion ratio) while carcass traits were not affected compared with those of rabbits fed the low crude protein level. But dietary supplements (nano-Se or glutamine) did not significantly affect criteria of growth performance or dressing-out percentage of rabbits. Dietary protein by added supplements interaction did not significantly affect traits, investigated in the present study, the whole experimental period. Based on the present results, it can concluded that the crude protein level (14%) is inadequate for attaining normal growth of post-weaning New Zealand White rabbits. However, dietary supplementation with nano-selenium or glutamine proved to be ineffective.

The role of four bioagents, i.e. Bacillus subtilis, Pseudomonas fluorescens, yeast (Saccharomyces cerevisiae) and Trichoderma viride, in controlling damping-off disease of bean (Phaseolus vulgaris L.) caused by Sclerotium rolfsii was evaluated under greenhouse and field conditions. The greenhouse experiment indicated that all the tested bioagents significantly reduced the incidence of the disease compared to control treatment. The most effective treatments were B. subtilis, T. viride and P. fluorescens which reduced disease incidence by more than 83.7 and 74.5% for pre- and post-emergence damping-off, respectively, while increased the plant survival by 90.3, 86.1 and 87.6%, respectively, compared to 26.3% in untreated plants. These treatments also increased the dry and fresh weights of bean shoot and root as well as resulted in considerable increases in the activities of peroxidase, polyphenoloxidase and chitinase by 260.0, 109.0 and 218.3%, respectively. Under field conditions, all the tested bioagents significantly reduced disease incidence with considerable increases in plant survival and higher seed yield during the two seasons (February of 2009 and 2010) of study. During the first season, B. subtilis T. viride, S. cerevisiae and P. fluorescens were found to be the most effective bioagents which reduced the disease incidence with more than 61.3 and 41.3% than the control for pre- and postemergence damping-off, respectively. The corresponding percentages of survived plants were 78.2, 79.0, 75.2 and 76.8%, respectively, viz. 38.5% for the control. On the other hand, the most effective treatments for increasing seed yield were S. cerevisiae followed by P. fluorescens, being 894.95 and 748.1 kg/feddan viz. 269.2 kg/feddan for the control. The other two bioagents showed moderate effect. The same trend was obtained during the second season. It could be suggested that such bioagents might be promising as alternatives to synthetic fungicides for controlling bean damping-off caused by S. rolfsii.

Chemical fungicides are effective tools in controlling plant pathogens; however, these chemicals can, on the other hand, distress the ecosystem. Accordingly, the current research investigates the potentiality of substituting traditional chemical fungicides by inducing plant resistance against infection with soil-born pathogens i.e. Sclerotium rolfsii in the presence of mycorrhizae (AMF) as plant inoculants and one of the following amendments: humic acid, sulphex (a mixture of canola oil and diluted sulphuric acid) and paclobutrazol (ABZ). To attain the abovementioned objective, a field (mildly infected with S. rolfsii) was cultivated with Helianthus tuberosus (a perennial plant belongs to the Asteraceae family) for two successive seasons (2014 and 2015) and the above-mentioned treatments were tested for their feasibilities in controlling S. rolfsii infection against the chemical fungicide “Vitavax-200” either solely or in combinations in a complete randomized block design. Inoculating plants with AMF or amending soils with either humic acid, Sulphex or ABZ solely increased significantly the activities of plant defense enzymes by approximately 1.5–2.1 folds higher than the control treatment. These treatments also improved NPK availability in soil and; hence, increased their contents within plant tubers. Consequently, these treatments decreased the disease incidence and severity caused by S. rolfsii while improved shoot biomass and tuber yield. In spite of that, these results stood below the prospective of the fungicide treatment. The integrated treatments i.e. “humic acid + AMF”, “Sulphex + AMF” and “ABZ + AMF” caused further significant improvements in both NPK availabilities in soil and plant areal bio-masses. This probably induced further plant resistance against the investigated soil-borne pathogen while recorded insignificant variations in disease incidence and severity when compared with the fungicide treatment. Moreover, the integrated treatments increased the tuber yields beyond those attained for the fungicide treatment. Accordingly, such integrated strategies can completely substitute the chemical fungicides; thus, minimize their negative impacts on the ecosystem.

Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers, including chondrosarcomas. IDH mutations detected in human cancers invariably are heterozygous missense substitutions. These mutations lead to the inability of IDH to convert isocitrate into α-ketoglutarate (α-KG). Instead, α-KG is reduced into 2-hydroxyglutarate (D-2HG), an oncometabolite. Due to the structural similarity between D-2HG and α-KG, it has been reported that high levels of D-2HG competitively inhibit α-KG-dependent dioxygenases such as TET, JHDM and PHD enzymes, thus contributing to tumorigenesis. We sought to determine the role of IDH1 mutations in the tumorigenesis of human chondrosarcomas by inactivating mutant IDH1 using pharmacological and genetic approaches. In our study, we employed two human chondrosarcoma cell lines, JJ012 and HT1080, that carry endogenous IDH1 mutations. IDH mutation analysis was performed by PCR-based DNA sequencing, and D-2HG levels were measured by tandem mass spectrometry. Mutant IDH1 was knocked down via siRNA and knocked out via CRISPR/Cas9. We analyzed the effect of mutant IDH1 on chondrosarcoma growth in murine xenograft models. We found that knockdown of mutant IDH1 via siRNA significantly reduced D-2HG production in chondrosarcoma cells. In addition, mutant IDH1 knockdown dramatically inhibited colony formation in the sarcoma cells. Consistently, genetic knockout of mutant IDH1 almost completely depleted D-2HG production and significantly inhibited colony formation in the chondrosarcoma cells. To assess the significance of these results in vivo, we implanted the mutant IDH1- knockout cells in nude mice and studied their capacity for tumor initiation and growth. In these models, we observed that loss of mutant IDH1 led to a marked attenuation of chondrosarcoma formation. Our findings clearly demonstrate that mutant IDH1 plays a vital role in chondrosarcoma tumor formation. By investigating the role of IDH mutations in the pathogenesis of chondrosarcomas, we aim to uncover the potential therapeutic targets against this aggressive cancer. Citation Format: Luyuan Li, Xiaoyu Hu, Josiane E. Eid, Joanna DeSalvo, Jonathan C. Trent. Mutant IDH1 is essential for chondrosarcoma growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 864.

Avian oncogenic viruses include Marek’s disease virus (MDV), a highly contagious herpesvirus, as well as retroviruses such as avian leukosis virus (ALV) subgroups A to J and reticuloendotheliosis virus (REV). In this study, we are surveying the incidence of these viruses during 2011-2015. A total of 64 flocks were vaccinated against MDV by using bivalent vaccine (HVT FC-126 + Rispens CVI988) (45 commercial Brown, white layers and 19 broiler breeder flocks) suffering from increase mortality with high No. of culling birds, bad uniformity and the post mortem examination revealed the presence of tumor lesions in different visceral organs. The age of birds varied from 11-24week, located in eight different governorates; [El-Sharkia, El-Dakahlia, El-Behera, Ismailia, Damietta, El-Monofia, El-Giza, Alexandria] .The total mortality reached 32.6% in brown commercial layers, 25.2% in white commercial layers (with average 28.9%) , 35.7% and 25.2% in females and males of broiler breeders respectively. Samples were collected from a total number of 20 out of 64 examined flocks, the twenty flocks representive 8, 6 and 6 commercial brown, white layer and broiler breeders respectively from tumor organs (liver, spleen, kidney, Bursa of Fabricious, heart, nerve, brain, mesentery and proventriculus). The histopathology-positive tissue sections were identified and further con-firmed by RT-PCR in addition to a blood samples were also collected for serological test using ELISA for ALV and REV. PCR using primers specific to (MDV, ALV, REV) appeared to be the method of choice for rapid and accurate diagnosis of these viruses. PCR and ELISA tests demonstrated the presence of MDV only in all collected samples except one sample was positive for both MDV and REV virus but all samples were negative for ALV.

Synovial sarcoma is an aggressive soft-tissue malignancy of children and young adults, with no effective systemic therapies. Its specific oncogene, SYT–SSX (SS18–SSX), drives sarcoma initiation and development. The exact mechanism of SYT–SSX oncogenic function remains unknown. In an SYT–SSX2 transgenic model, we show that a constitutive Wnt/β-catenin signal is aberrantly activated by SYT–SSX2, and inhibition of Wnt signaling through the genetic loss of β-catenin blocks synovial sarcoma tumor formation. In a combination of cell-based and synovial sarcoma tumor xenograft models, we show that inhibition of the Wnt cascade through coreceptor blockade and the use of small-molecule CK1α activators arrests synovial sarcoma tumor growth. We find that upregulation of the Wnt/β-catenin cascade by SYT-SSX2 correlates with its nuclear reprogramming function. These studies reveal the central role of Wnt/β-catenin signaling in SYT–SSX2-induced sarcoma genesis, and open new venues for the development of effective synovial sarcoma curative agents. Significance: Synovial sarcoma is an aggressive soft-tissue cancer that afflicts children and young adults, and for which there is no effective treatment. The current studies provide critical insight into our understanding of the pathogenesis of SYT–SSX-dependent synovial sarcoma and pave the way for the development of effective therapeutic agents for the treatment of the disease in humans. Cancer Discov; 3(11); 1286–1301. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 1207

Summary Background We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. Methods In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m 2 intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1–14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. Findings Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87–8·40) in the vorinostat group and 6·83 months (5·67–7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64–0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most common grade 3–4 adverse events were thrombocytopenia (143 [45%] patients in the vorinostat group vs 77 [24%] patients in the placebo group), neutropenia (89 [28%] vs 80 [25%]), and anaemia (53 [17%] vs 40 [13%]). Interpretation Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo, the clinical relevance of the difference in PFS between the two groups is not clear. Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity. Funding Merck.