Artículos de revistas sobre el tema "300.72/3"

One of the most prominent natural resources in Congko Village is agricultural land of around 300.72 hectares, while the area of plantation land managed by the Bulu Mappalasae farmer group reaches 101 hectares consisting of 21 hectares of corn land, 63 hectares of cocoa/cocoa land, and 17 hectares of rice fields. The results of the plantation are unsatisfactory, namely for the cocoa plantation which is only able to produce 500kg/hectare/year. One of the obstacles to the lack of productivity of agricultural products is due to the lack of fertilizer, the amount of fertilizer obtained by farmers averages 600kg / hectare, while the fertilizer needed by farmers averages 1 ton / hectare or a total of 63 tons from a land area of 63 hectares. Apart from agricultural activities, there are also livestock activities owned by the community. With the livestock business, the community can make this a potential area. However, the problem in animal husbandry is that livestock waste/dung increases every day and pollutes the environment because it is not managed properly, but if livestock waste/dung can be managed properly, it can provide great benefits to the community such as biogas management from livestock manure which produces gas and organic fertilizer. The solution to the existing problems is to integrate farming and livestock to make organic fertilizer and apply the technology of making biogas from livestock manure. To implement the solution, an implementation method was prepared, namely conducting training and mentoring in making organic fertilizer and managing livestock manure into biogas and organic fertilizer using a bidiogester. From the results of processing waste into organic fertilizer, there are organic fertilizer products that are ready to be applied to agricultural land and produce 3 tons of organic fertilizer / month. And the results of managing livestock manure produce 540kg/month of biogas and 2.3 tons/month of organic fertilizer.

Slow-release bioplastic fertilizer (BpF) composites were developed by processing oil palm empty fruit bunch (EFB), fertilizer, and poly(hydroxybutyrate-co-valerate) (PHBv) using extrusion techniques with controlled formulation and temperature. The temperature was kept at 150°C for 3 to 5 min during processing using twin-screw extruder. The PHBv lost weight gradually with the increasing temperature and its thermal degradation occurred initially at 263.4°C and reached the maximum at 300.7°C. Scanning electron microscope (SEM) images showed that the bonding of all composites created small gaps between matrices polymer and fiber because the hydrophilic characteristic of EFB fibers weakened the interfacial bonding. PHBv/EFB/NPKC2 showed faster biodegradation over PHBv/NPKC1 and PHBv/NPKC2, which was 99.35% compared to 68.66% and 90.28%, respectively.

Eighteen commercially used white Antirrhinum majus (snapdragon) inbreds, a hybrid of Inbred 1 × Inbred 18 (Hybrid 1) and an F2 population (F2) of Hybrid 1 were evaluated for stomatal size and density and transpiration rate to determine their affect on postharvest longevity. Stems of each genotype were cut to 40 cm, placed in distilled water and discarded when 50% of florets wilted or browned. Postharvest longevity of inbreds ranged from 3.7 to 12.9 days; Hybrid 1 and the F2 averaged 3.0 and 9.1 days postharvest, respectively. Leaf impressions showed less than 3% of stomata were found on the adaxial leaf surface. Inbred abaxial stomatal densities ranged from 128.2 to 300.7 stomata mm-2; Hybrid 1 and the F2 averaged 155 and 197 stomata mm-2, respectively. Transpiration measurments on leaves of stems 24 hr after cutting were made with a LI-COR 1600 Steady State Porometer. Statistical analysis showed inbreds were significantly different based on postharvest longevity, stomatal size and density and transpiration of cut stems.

For the functional food applications, antioxidant properties and the bioactive compounds of the 23 Curcuma species commercially cultivated in Thailand were studied. Total phenolic content and DPPH radical scavenging activity were determined. The concentrations of eight bioactive compounds, including curcumin (1), demethoxycurcumin (2), bisdemethoxycurcumin (3), 1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (4), germacrone (5), furanodienone (6), zederone (7), and ar-turmerone (8), were determined from the Curcuma by HPLC. While the total phenolic content of C. longa was highest (22.3 ± 2.4 mg GAE/g, mg of gallic acid equivalents), C. Wan Na-Natong exhibited the highest DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) radical scavenging activity. Twenty-three Curcuma species showed characteristic distributions of the bioactive compounds, which can be utilized for the identification and authentication of the cultivated Curcuma species. C. longa contained the highest content of curcumin (1) (304.9 ± 0.1 mg/g) and C. angustifolia contained the highest content of germacrone (5) (373.9 ± 1.1 mg/g). It was noteworthy that 1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (4) was found only from C. comosa at a very high concentration (300.7 ± 1.4 mg/g). It was concluded that Thai Curcuma species have a great potential for the application of functional foods and ingredients.

Purpose: The aim of the present investigation was to formulate protein nanoparticles loaded suppositories for colon targeting of metronidazole (MZ), to achieve sustain release effect. Methods: Protein nanoparticles were formulated via desolvation technique by utilizing 2 3 factorial design which results into eight formulations. The synthesized protein nanoparticles were characterized for different physicochemical and in vitro parameters viz. particle size, surface morphology, entrapment efficiency and zeta potential, drug- excipients compatibility studies. Results: The formulated protein nanoparticles were found to be spherical in shape and have an average size in the range of 300.7 nm to 504.8 nm. Based on the results obtained, F7 was found to be the optimized formulation that was loaded into the suppository base. Furthermore, suppositories were also characterized for several parameters like content uniformity, weight variation and liquefaction time. Conclusion: Resultant, suppositories were free from pits, fissures and cracks. The in-vitro release data of metronidazole protein nanoparticles (MZ-PNPs) loaded suppositories were compared with the suppositories loaded with active ingredient only i.e. metronidazole. Screening against Pheretima posthuma was also conducted. The results of in vitro drug release testing proved that protein nanoparticle loaded suppositories is a better approach, compared to pure metronidazole loaded suppositories. Release kinetic study concluded that the formulation follows higuchi’s equation i.e. having a biphasic release pattern. The efficiency of the formulated dosage form was evaluated using Indian earthworms, Pheretima posthuma (P. posthuma).

Purpose. To investigate the long-term changes of corneal endothelial cells (EC) in anterior chamber intraocular lens- (AC-IOL-) implanted eyes. Methods. Retrospective study. We included 37 eyes (25 patients) that received AC-IOL implantation previously in the Eye and ENT Hospital of Fudan University between 1995 and 2016. Follow-up outcomes included the best-corrected visual acuity (BCVA), endothelial cell density, hexagonality, coefficient of variance, and central corneal thickness. Results. In total, 23 eyes (62.16%) with phakic and 14 eyes (37.84%) with aphakic AC-IOLs were included. Among these, 3 eyes (8.11%) were angle-supported AC-IOLs and 34 eyes (91.89%) were Artisan iris-fixated AC-IOLs. The mean age of patients was 41.40 ± 17.17 years, and the mean follow-up time was 12.12 ± 4.71 years in our study. At the follow-up time, corneal decompensation existed in 3 angle-supported AC-IOL eyes with a rate of 100% and 15 iris-fixated AC-IOL eyes with a rate of 44.12%. AC-IOL displacement occurred in 14 (41.18%) iris-fixated AC-IOL eyes. In the 19 iris-fixated AC-IOL eyes without corneal decompensation, significant changes also took place in corneal endothelial cells. The endothelial cell density decreased from 2843.26 ± 300.76 to 2015.58 ± 567.99 cells/mm2 (29.1% loss, P < 0.001 ) and hexagonality decreased from 51.21 ± 7.83 to 42.53 ± 9.17 (%) (16.9% loss, P < 0.001 ). The Kaplan–Meier survival curve also demonstrated the accumulated expectation rates of corneal endothelial cell decomposition for AC-IOLs with a median survival time of 12 years. Conclusion. We reported a significant chronic loss and long-term decompensation destiny of corneal endothelial cells in AC-IOL eyes. Semiannual or annual follow-up and evaluation of endothelial cells should be conducted in AC-IOL-implanted patients.

Abstract The study was carried out in the certified citrus propagation nursery of the Horticultural and Forestry Company in Al-Hindiya District / Holy Karbala Governorate during the period 20/4/ up to 20/8/2021, in order to study the effect of adding bio-fertilizer and spraying nano and chelated iron fertilizers on the content of orange seedlings leaves of the elements food. The experiment included three factors, the first biological fertilizing factor, adding ground at four levels, which are (the comparison treatment, azotobacter, mycorrhizal fungi, mycorrhizal fungi + azotobacter). It is the spraying of chelated iron in three levels (zero, 3, and 6 g / liter). A factorial experiment was carried out with a Randomized Complete Block Design, and the averages of traits were compared with the L.S.D. test at the 5% probability level. The results indicated: The biofertilization treatment (Mycorrhizal fungus+ Azotobacter bacteria). And the spraying treatment with nano iron fertilizer (3 g. L-1) was significantly superior in the content of orange seedlings leaves of nutrients (Zn,Fe,K,P,N) and the spraying treatment was The chelated iron fertilizer (6g.l-1) showed the same behavior and showed significant differences in the content of nutrients in the leaves. It gave the highest concentrations of the studied elements. The dual interactions between the study factors gave significant differences in the school characteristics, as it gave the treatment (Azotobacter + Mycorrhizae) + spraying of nano iron (3 g. L-1), and biological fertilization (Azotobacter + Mycorrhizae) + spraying of chelated iron (6 g. L-1), And (nano iron spray (3 g.l-1) + chelated iron spray (6g.l-1) the highest values are superior to the rest of the treatments and reached (2.58%, 0.68%, 2.81%, 300.79 mg. kg-1. dry weight, 42.80 mg. kg-1.d.w.) (2.55%, 0.64%, 2.97%, 297.79 mg. kg-1. d.w., 42.19 mg. kg-1. d.w.) (2.49%, 0.62%, 2.74%, 256.17 mg kg-1 dry weight, 39.66 mg kg-1 dry weight, respectively, gave the triple interaction treatment (Azotobacter + Mycorrhizae) + spray of nano iron (3 g. L-1) + spray of chelated iron (6 g). L-1) was significantly superior in leaf content of the studied elements, and it reached (2.77%, 0.75%, 3.20%, 309.17 mg. kg-1. dry weight, 49.40 mg. kg-1. dry weight), respectively.

14116 Background: We have previously reported that O-LM inhibits malignant cell proliferation and increases survival in rodent tumor models (Int J Cancer S13:183, 2002). Molecular and immunological basis of O-LM action were reported (J Clin Oncol 24:18S, 2006). As O- LM selectively protects normal tissues from high doses of ionizing radiation (Proc Int Cancer Congress,1495–9, 1998), we here investigated O- LM protective action upon radiation effects on immune cells. Methods: Balb/c mice (n=15 each group) were employed: control (C); 2Gy whole body irradiated (IR); treated with O-LM (Zn, Se, Mn 4μg/ml each; L. Muta 4 ng/ml; 0.1 ml/day, sc) for 15 days and 2Gy irradiated (O-LM+IR). Mice were sacrificed at day 3, 7 or 15 post-irradiation (PI). Proliferation was evaluated in lymphocytes by [3H]- Thymidine incorporation after T- or B selective mitogen stimulation. In cell-free supernatants (SN) from mitogen-stimulated cultures cytokines involved in lymphocyte regulation and/or inflammation were determined by ELISA. Results: Irradiation induced a decrease in T lymphocyte proliferation at 3 and 7 days PI (% of decrease in IR: 47.6±9.0, p<0.05; 42.0±7.2, p<0.02 respectively). Pretreatment with O-LM recovered proliferation to basal values (day 3 PI 93.4±10.2%; day 7 PI 130.9±15.3%, O-LM+IR vs. C; p=NS). No modifications were observed in B cells. At day 3 PI, a marked decrease in IFN? levels was obtained in SN of IR mice that was reverted by O-LM treatment (pg/ml: IR 1653±419; C 10884±2783, p<0.02; O-LM+IR 16924±4284, p<0.05 vs C). Also, at day 7 PI, an important increase in TNFa was observed in IR mice, that were reverted by O-LM (pg/ml: IR: 300.7±62.3 vs O-LM+IR: 28.7±2.3, p<0.02). No differences were found in IL-2 levels. Conclusions: The therapeutic action of O-LM is based on its ability of targeting simultaneously multiple pathways involved in cancer development. Present data demonstrate that O-LM protects animals from irradiation by recovering the immune function, improving T lymphocyte activity and modulating the production of key cytokines as IFN? and TNFa. The reported effect may represent a potential benefit for cancer patients undergoing radiotherapy. No significant financial relationships to disclose.

Purpose To evaluate the effect of intravitreal triamcinolone acetonide on visual acuity and macular thickness using optical coherence tomography (OCT) in macular edema associated with various retinal vascular disorders. Methods This prospective nonrandomized clinical interventional study included 81 eyes (76 patients) comprised of Group I, 57 eyes (51 patients) with diabetic macular edema; Group II, 10 eyes (10 patients) with branch retinal vein occlusion; and Group III, 13 eyes (13 patients) with central retinal vein occlusion. All eyes received an intravitreal injection of 4 mg triamcinolone acetonide (with the solvent) in the operation theater under sterile conditions. Results Mean preinjection central macular thickness was 531.84±132 μm in Group I, 458.4±149 μm in Group II, and 750.81±148 μm in Group III. All groups showed a statistically significant decrease in mean central macular thickness at 1 month (300.7±119 μM in Group I, 218.2±99 μm in Group II, and 210.5 ±56 μm in Group III) and 3 months (253.19±109 μm in Group I, 187±47 μm in Group II, and 182±50 μm in Group III) after injection (p<0.05). Mean follow-up was 22±2.4 weeks. Mean visual acuity increased in all three groups (preoperative visual acuity in Group I, 1.2±0.4 logMAR units; Group II, 1.24±0.5 logMAR units; Group III, 1.1 ±0.4 logMAR units; 1 month postinjection in Group I, 0.88±0.3 logMAR units; Group II, 0.67±0.3 logMAR units; Group III, 0.86±0.4 logMAR units; 3 months postinjection in Group I, 0.84±0.4 logMAR units; Group II, 0.59±0.3 logMAR units; Group III, 0.82±0.5 logMAR units) (p<0.05). Forty-one eyes completed 6 months and 20 eyes completed 9 months follow-up. Twelve of 20 (41%) eyes in Group I, 2/6 (33%) eyes in Group II, 3/6 (50%) eyes in Group III, and 8/15 (53%) eyes in Group I, 1/3 (33%) eyes in Group II, and 2/2 (100%) eyes in Group III developed recurrence of macular edema with worsening of visual acuity at 6 and 9 months, respectively. Thirty-three (40.7%) eyes developed IOP elevation (at least one reading > 24 mmHg). One eye developed infective endophthalmitis. Conclusions Intravitreal injection of triamcinolone acetonide may be considered as an effective treatment for reducing macular thickening due to diffuse diabetic macular edema, venous occlusion associated macular edema, and may result in increase in visual acuity at least in the short term. Further follow-up and analysis is required to demonstrate its long-term efficacy.

Abstract Abstract 2111 Pathogenic bacteria must acquire iron from their hosts to survive and have evolved multiple mechanisms to capture iron or iron-containing heme from the bloodstream or tissues. In response, mammals have developed defense mechanisms to keep iron from pathogens. For example, in response to inflammatory cytokines, hepcidin secreted by the liver binds to the iron exporter ferroportin (FPN1), leading to FPN1 internalization and degradation, decreasing gastrointestinal iron absorption and increasing macrophage iron storage. Much of the body's iron stores are complexed in heme. The Feline leukemia virus, subgroup C (FeLV-C) receptor, FLVCR, is a heme export protein. We showed previously that FLVCR is required for the normal development of the erythroid [Science (2008)319:825] and T cell lineages [Blood (ASH Annual Meeting Abstracts)114:913,2009]. Although macrophages express high levels of FLVCR, the role of FLVCR in regulating heme-iron after infection remains unexplored. Other heme regulatory proteins, such as heme oxygenase-1 (HMOX1), a heme-degrading enzyme, are known to be transcriptionally regulated in macrophages in response to infection. We hypothesized that macrophages dynamically regulate Flvcr in response to bacterial infection. To test this hypothesis, we stimulated J774, a murine macrophage cell line, with lipopolysaccharide (LPS from E. coli O111:B4) at varying concentrations and durations. LPS, an outer membrane component from gram-negative bacteria, binds to Toll-like receptor 4 (TLR4) on macrophages and activates downstream signaling pathways. Using multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR), we measured mRNA levels of Flvcr, Hmox1, and Fpn1. We found that J774 cells down-regulated Flvcr transcript levels in response to LPS with a maximal decrease (69%) seen at 6–8 hours of stimulation. While the extent of Flvcr down-regulation was dose-responsive, a significant decrease (57%) occurred even with the lowest LPS dose (10 ng/ml). Macrophages decreased Fpn1 expression (71%) and increased Hmox1 expression (55%) in response to LPS stimulation as previously reported. Similar results were obtained with LPS from a different bacterial source (Salmonella minnesota Re595). We also performed these studies using primary macrophages cultured from murine bone marrow mononuclear cells and observed a similar decrease in Flvcr and Fpn1 (64 and 72%) and an increase in Hmox1 (40%) transcripts after stimulation with both O111:B4 and Re595 LPS. While Fpn1 transcriptional regulation by heme and oxidative stress has been studied, the mechanism by which LPS regulates Fpn1 transcription is less clear. The similar pattern and kinetics of LPS-induced Flvcr and Fpn1 expression changes raise the possibility that the same regulatory mechanism is responsible. Analysis of the human and mouse Flvcr promoter regions revealed several putative LPS downstream transcription factor binding sites including NF-κB, AP1, and C/EBPβ. In addition to transcriptional regulation, LPS downstream signaling could alter Flvcr and Fpn1 mRNA stability and translation, so we compared the 5' untranslated regions (UTR) and 3'UTR of murine Flvcr and Fpn1. We found little similarity between the 5'UTR of Flvcr and the 5'UTR of Fpn1, known to contain an iron-responsive element (IRE) and be regulated by iron via iron regulatory proteins (IRP). However, alignment of the 3'UTR from Flvcr and Fpn1 showed similarity (pair wise score 65). Both the Flvcr and Fpn1 3'UTR are predicted to have a high degree of secondary structure based on their large negative fold energies (−421.25 and −300.74 kcal/mol), further suggesting that these 3'UTR may have a regulatory function. Studies are underway to determine the roles of the Flvcr promoter, 5'UTR, and 3'UTR in LPS-induced down-regulation. This work suggests that LPS-induced down-regulation of Flvcr and Fpn1 might act in concert to decrease heme and iron export from macrophages and sequester iron from bacterial pathogens. Heme export control through FLVCR could serve as a novel mechanism of iron regulation in response to infection. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Recent trends indicate a change in the epidemiology of inflammatory bowel disease (IBD) with previously low incidence areas now reporting progressive rise. The number of epidemiological population-based studies are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to analyze the incidence and disease phenotype at diagnosis, and the maximal therapeutic step distributions during follow-up in a prospective population-based database from Veszprem Province, including incident ulcerative colitis (UC) patients diagnosed between January 1, 2007 and December 31, 2018. Methods Data of 467 incident UC patients were analyzed (male/female:236/231; median age at diagnosis:36 years(y)[IQR: 25–54]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The source of age- and gender-specific demographic data for statistical analysis was derived from the results of a national population census in 2011. Results Adjusted mean incidence rate was 11.02(CI95%:10.1–12.1)/105 person-years in this 12 year period[males:11.53(CI95%:10.2–13.1)/105; females:10.54(CI95%:9.3–12.0)/105]. Prevalence rate was 283.51(CI95%:265.7–300.7)/105 persons in 2011 and 317.79(CI95%:298.8–335.8) in 2015. For detailed annual incidence rates and age-specific mean incidence rates see Figure 1 and 2. Peak onset age in UC was 20–29 years of age. Diagnostic delay from symptom onset was ≥1year in 19.1%, and ≥3 years in 4.1% of the patients. Disease extension was proctitis(E1) in 22.3%, left sided colitis(E2) in 43.9%, and extensive colitis(E3) in 33.8% of the patients at diagnosis. Patients with extensive colitis were younger(32.9y,SD:16.6) at diagnosis compared to patients with proctitis(40.1y,SD:15.9;p&lt;0.001) or left sided colitis(44.0y;SD:19.1;p&lt;0.001). Extraintestinal manifestations were as follows: hepatic5.4%(PSC 2.1%), arthritis10.7%, ocular0.9%, skin3.6%. Active smokers at diagnosis were 12.6%. Distribution of maximal therapeutic steps during the course of follow-up (8.34y,SD: 3.5) were 5-ASA in 46.9%, systemic corticosteroids in 16.3%, immunosuppressive therapy in 19.3%; anti-TNF biologic therapy in 12.2% and other biologic therapy in 4.3%. Conclusion The incidence of UC in this 12 year period was high, comparable to high-incidence areas in Western European countries, and comparable to previous data from the Veszprem cohort, while prevalence rates continue to rise compared to our previous data.(Lakatos 2011, IBD). Disease extension at diagnosis and distribution of highest treatment step was comparable to European population-based data.(Burisch 2019, JCC).

Abstract Introduction A specific antibody fragment (Fab) is currently in development to reverse the effects of dabigatran in cases of life-threatening bleeding or emergency surgery. In trauma, different volume expanders are used for resuscitation to compensate for blood loss and hemorrhagic shock. The influence of volume expanders on binding of dabigatran to the Fab, however, is not known. Therefore, in this study we investigated whether frequently used infusion solutions affect binding of dabigatran to the Fab antidote and the resulting effects on coagulation assays. Methods All studies were performed after ethical approval. Dabigatran etexilate was given to pigs for 3 days (30 mg/kg bid) and on day 4 a 90 min infusion of dabigatran (30 min:0.77mg/kg/h; 60 min:0.26 mg/kg/min) was performed in anesthetized pigs. Then ∼50% (100 mL/min) of total blood volume was removed and animals were randomized to (n=5/group): balanced Ringer’s solution, 6% HES 130/0.4, 6% HES 200/0.5, 4% gelatin, retransfusion of washed red blood cells (RBCs) or control (no haemodilution). Resuscitation consisted of, 1:1 to blood loss for crystalloids, 25 mL/kg for colloids, and 12 mL/kg for RBC. Antidote was then given (30 mg/kg iv) and serial blood samples were taken for up to 24 hrs to measure active dabigatran as diluted TT (Hemoclot) and total dabigatran (LC-MS/MS). Coagulation was assessed by means of aPTT, diluted PT (dPT, Neoplastin R, 1:100), i-Stat ACT celite (ACT), and ROTEM, ExTem and InTem reagents. Data expressed as mean ± SE and analyzed with ANOVA. Results Hemodilution resulted in a substantial reduction of hemostatic parameters (Hemoglobin, platelets and leukocytes) with all agents, except after RBC transfusion vs control. Mean plasma dabigatran levels measured at dTT were 640 ± 60 ng/mL after infusion and 625 ± 123 ng/mL after hemodilution without significant differences between groups. Administration of 30 mg/kg iv Fab resulted in a comparable reduction of active dabigatran in all groups, with a calculated half-life of 3.2 ± 0.1 hrs. The best correlation between dTT and other coagulation assays was obtained for the dPT (r2=0.6321), the ACT-celite (r2=0.6605) and clotting time from ExTEM and InTEM ROTEM (r2=0.5169 and 0.7303, respectively). The correlation between aPTT and dTT was moderate: r2=0.2321. Overall, coagulation was prolonged upon dabigatran treatment as indicated by the dPT (from 32.3±10.6 to 162.7±18.1 sec), aPTT (fom 44.6±6.2 to 67.9±10.3 sec), ACT (from 97±6 to 297±25 sec), CT ExTem (from 36.5±3.7 to 1205.4±598.3 sec) and CT InTem (from 122.0±11.9 to 989.3±218.9 sec). Fab treatment restored coagulation by on average 73% (between 58 and 95%, depending on the applied assay) at 5 minutes following administration. The dPT shortened to 43.8±24.1 sec, the aPTT to 30.6±5.5 sec, the ACT to 126±25 sec, the CT ExTem to 124.3±83.4 sec, and the CT InTem to 300.7±168.7 sec, with no significant differences in coagulation parameters between the various volume expanders. However, resuscitation with 4% gelatin and Fab treatment resulted in a significant lesser reduction of the CT InTem compared to the other volume expanders: 631.6±360.4 sec for 4% gelatin and 203.8±22.4, 251.7±157.2, and 280.8±235.3 sec for 6% HES 200/0.5, 6% HES 130/0.4, and Ringers, respectively. All coagulation parameters were comparable between the various volumes expanders from 60 minutes onward. Twenty four hours after Fab administration all coagulation parameters were almost back to baseline values with 26.9±62.8 ng/mL dabigatran, 50.9±12.6 sec for the dPT, 48.6±13.5 sec for the aPTT, 121±6 sec for ACT, 50.0±3.4 sec for CT ExTem, and 189.7±24.5 sec for CT InTem. Conclusions Clinically used infusion solutions for volume resuscitation do not interfere with binding of dabigatran to its specific antidote. Inhibition of dabigatran with its specific Fab antidote at this particular dose, restored coagulation by almost 70% This effect was independent of the volume applied for resuscitation. Disclosures: Spronk: Boehringer Ingelheim Pharma GmbH & Co. KG: Research Funding. van Ryn:Boehringer Ingelheim Pharma GmbH & Co. KG: Employment. Grottke:Boehringer Ingelheim Pharma GmbH & Co. KG: Research Funding.

Background:Infections are the most common adverse event of Tocilizumab (TCZ) in Giant Cell Arteritis (GCA). In GiACTA study(1),serious infections were observed in 7% (9.6/100 patient-years) of patients who received TCZ weekly. Randomized clinical trials (RCTs) are conducted under highly standardized design excluding some real-world patients. Therefore, adverse events may be underestimated in RCTs. In our series of real-life, serious infections occurred in 11.9% (10.6/100 patient-years)(2).Objectives:In a wide series of GCA of clinical practice treated with TCZ, we assess the frequency, type and predisposing factors of serious infections.Methods:Multicenter study of 134 patients diagnosed with GCA, all of them refractory to conventional therapy, treated with TCZ. Serious infection was considered when a life-threatening infection, fatal, or requiring hospitalization occurred, intravenous antibiotics were required, or the infectious process led to persistent or significant disability.Results:16 of 134 (11.9%, 10.6/100 patient-years) patients developed serious infections during follow-up. The most frequent infections were pneumonia (n=4), urinary tract infection (n=4), and facial herpes zoster (n=2). At TCZ onset, serious infections were more frequent in older patients (74.3±9.6 vs 72.9±8.7 years), with a longer GCA evolution (20 [4.3-45.6] vs 13 [5-29.3] months), with visual manifestations (43.75% vs 17.8%) and a higher dose of prednisone at TCZ onset (30.4±15.5 vs 21.1±16.1 mg/day) (TABLE). Presence of comorbidities were similar in both groups. 13 of the 16 patients who had infections received a dose of prednisone greater than 15 mg/day (16.3/100 patient-years) compared to 3 patients under treatment with less than 15 mg/day of prednisone (4.2/100 patient-years).Conclusion:The age, GCA duration, ocular involvement and the dose of glucocorticoids, at TCZ onset, seem to be predisposing factors related to an increased risk of developing serious infections in GCA patients.References:[1]Stone JH, et al. N Engl J Med. 2017; 377:317-28.[2]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLESERIOUS INFECTIONS(n=16)WITHOUT SERIOUS INFECTIONS(n=118)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURES Age, years, mean± SD74.3±9.672.9±8.70.552 Sex, female/male n(%)13/388/300.760 Time from GCA diagnosis to TCZ onset (months), median [IQR]20[4.3-45.6]13[5-29.3]0.604COMORBIDITIES Hypertension, n(%)9(56)86(73)0.551 Diabetes, n(%)3(19)39(33)0.677 Chronic kidney disease, n(%)3(19)27(23)0.512CLINICAL FEATURES OF GCA PMR, n(%)9(56.25)64(54.2)0.879 Aortitis, n(%)5(31.25)53(45)0.301 Visual manifestations, n(%)7(43.75)21(17.8)0.017CORTICOSTEROIDS AT TCZ ONSET Prednisone dose mg/d, mean (SD)30.4±15.521.1±16.10.031Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, Carmen González-Vela: None declared, Javier García-Fernández: None declared, Patricia Vicente-Gómez: None declared, Ángel García-Manzanares: None declared, Norberto Ortego: None declared, Francisco Ortiz-Sanjuán: None declared, Montserrat Corteguera: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:The efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, in patients (pts) with active psoriatic arthritis (PsA) were demonstrated through 24 weeks in the phase 3 SELECT-PsA 1 and SELECT-PsA 2 placebo-controlled clinical trials.1,2Objectives:To describe the long-term integrated safety profile of UPA relative to adalimumab (ADA) in pts with PsA treated in the SELECT program.Methods:The SELECT-PsA program enrolled pts with prior inadequate response or intolerance to ≥1 non-biologic DMARD (SELECT-PsA 1) or ≥1 biologic DMARD (SELECT-PsA 2). Both trials include UPA 15 mg and 30 mg, and only SELECT-PsA 1 includes long-term comparison with ADA 40 mg every other week. Treatment-emergent adverse events (TEAEs: AE onset ≥first dose and ≤30 days after last dose for UPA and ≤70 days for ADA) were summarized for the following: pooled UPA 15; pooled UPA 30; and ADA. TEAEs are reported as exposure-adjusted event rates (EAERs; events/100 pts years [E/100 PY]) up to a cut-off date of 20 June 2020.Results:2257 pts received ≥1 dose of UPA 15 (N=907; 1247.2 PYs), UPA 30 (N=921; 1257.4 PYs), or ADA (N=429; 549.7 PYs), with median (max) exposures of 69 (155), 69 (154), and 68 (152) weeks, respectively. EAERs of TEAEs and serious AEs were generally similar between UPA 15 and ADA and higher with UPA 30; rates of AEs leading to study drug discontinuation were generally similar across all groups (Table 1). Similarly, rates of serious infection were comparable between UPA 15 and ADA and higher with UPA 30 (Figure 1 next page). The most common serious infection was pneumonia. Rates of herpes zoster were lower with UPA 15 than UPA 30 but higher than ADA. Most herpes zoster events involved a single dermatome; no events involved the central nervous system or other internal organs. Lower rates of opportunistic infections (OI) excluding tuberculosis were observed with UPA 15 vs UPA 30; the most common OI was mucosal candida infection. Malignancies were reported at similar rates across all treatment groups; no events of lymphoma were reported. Age-gender-adjusted standardized incidence ratios for malignancies excluding NMSC indicated no increased risk with UPA compared to the general population. Rates of adjudicated major adverse cardiovascular events and venous thromboembolic events were ≤0.3 E/100 PY for both UPA arms; all pts had ≥1 risk factor. One adjudicated gastrointestinal perforation was reported with UPA 15.Table 1.Overall Treatment-emergent AEs for Upadacitinib and Adalimumab (E/100 PY [95% CI])UPA 15 mg QDN=907(1247.2 PY)UPA 30 mg QDN=921(1257.4 PY)ADA 40 mg EOWN=429(549.7 PY)AEs263.9 (254.9, 272.9)321.5 (311.6, 331.5)286.5 (272.4, 300.7)Serious AEs10.3 (8.6, 12.1)13.2 (11.2, 15.2)9.6 (7.0, 12.2)AE leading to discontinuation6.7 (5.2, 8.1)7.8 (6.2, 9.3)7.8 (5.5, 10.2)Deathsa0.2 (-0.1, 0.4)0.2 (-0.0, 0.5)0.2 (-0.2, 0.5)aDeaths included non-treatment emergent deaths: UPA 15, 1; UPA 30, 1.ADA, adalimumab; AE, adverse event; CI, confidence interval; E, event; EOW, every other week; PY, patient years; QD, once daily; UPA, upadacitinib.Hepatic disorders were mostly transient, non-serious transaminase increases. Creatine phosphokinase elevations were reported more frequently with UPA 30 vs UPA 15; most were asymptomatic with no rhabdomyolysis reported. AEs of anemia, neutropenia, and lymphopenia were generally mild or moderate, non-serious. Except for rates of lymphopenia (higher with UPA 15), hepatic disorders, and neutropenia (both higher with ADA), lab-related TEAEs occurred at generally consistent rates between UPA 15 and ADA. Study drug discontinuation due to lab-related TEAEs was uncommon.Conclusion:The safety profiles of UPA 15 and ADA were generally similar; the rates of most AEs were higher with UPA 30 compared with ADA. Through the cut-off date, the safety profile of UPA 15 and UPA 30 in PsA pts demonstrated consistent results compared to what has been observed with UPA in rheumatoid arthritis.3References:[1]McInnes IB et al. Ann Rheum Dis, 2020; 79:12.[2]Mease PJ et al. Ann Rheum Dis, 2020.[3]Cohen SB et al. Ann Rheum Dis, 2020.Figure 1Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc.Disclosure of Interests:Gerd Rüdiger Burmester Speakers bureau: AbbVie, Gilead, Lilly, Pfizer, Consultant of: AbbVie, Gilead, Lilly, Pfizer, Kevin Winthrop Consultant of: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Grant/research support from: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Ricardo Blanco Consultant of: Abbvie, Lilly, Novartis, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Grant/research support from: Abbvie, MSD and Roche, Peter Nash Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Philippe Goupille Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Valderilio F Azevedo Consultant of: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Grant/research support from: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Carlo Salvarani Consultant of: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Grant/research support from: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Andrea Rubbert-Roth Consultant of: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Grant/research support from: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: AbbVie, Employee of: AbbVie, Bosny Pierre-Louis Shareholder of: AbbVie, Employee of: AbbVie, Sandra Walko Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.

Phytochemicals found in extracts obtained from plants are very important bioactive constituents. In this study, phytochemicals in extract content obtained from Celtis tournefortii .Lam. tree (CT) leaves were determined by a LC-MS method. The constituents with the major concentrations was found rutin (2479.89 µg ml-1), coumarin (1241.68 µg ml-1), biochanin A (1026.42 µg ml-1), shikimic acid (477.32 µg ml-1), chlorogenic acid (300.76 µg ml-1). The suppressive effects of CT extract on the growth of pathogenic strains were studied by microdilution method. It was observed that it caused suppression on the strains in the concentration range of 2.00-8.00 µg ml-1. The inhibition effects of the extract on acetyl cholinesterase and glutathione-S transferase enzyme activities were investigated, and 50% inhibitory values of enzyme activity were found to be 13.58 and 13.86, respectively. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method, the cell viability suppressive effects of CT leaf extract were studied in healthy skin fibroblast cells as well as ovarian, colon and brain cancer cells. It was observed that they created a 42%, 4.27%, and 14.29% suppression in cells, respectively.

This research aimed to obtain the best nori from a mixture of Sargassum sp and Eucheuma spinosum seaweed and the most preferred by panellists. The research's method used in this study is an experimental method with 3 treatments comparing the seaweed between Sargassum sp. and Eucheuma spinosum that is 1:1, 2:1, 3:1 then tests that used are hedonic test with 20 semi-trained panellists who have experience in organoleptic assessment as replications, physical and chemical tests were also tested for the best treatment according to hedonic test. This research was conducted at the Fisheries Product Processing Technology Laboratory of the Faculty of Fisheries and Marine Sciences, Universitas Padjadjaran, while the chemical and physical testing of the final results of the research was conducted at the Laboratory of Biological Resources and Biotechnology at LPPM Institut Pertanian Bogor. This research was conducted on February 28, 2019, until March 8, 2019. Based on the results of the research level of preference of nori, it was found that all treatments carried out were still acceptable to the panellists, but the treatment with a ratio of 1: 1 was more preferred by panellists. Chemical characteristics of the Sargassum sp. and Eucheuma spinosum, namely water content contained in the amount of 15.67%, crude fibre content of 11.7% and physical characteristics of the hardness of 300.78 gf, also thickness with nori 0.347 mm.

AbstractAldo‐keto reductases (AKRs) are important biocatalysts that can be used to synthesize chiral pharmaceutical alcohols. In this study, the catalytic activity and stereoselectivity of a NADPH‐dependent AKR from Kluyveromyces dobzhanskii (KdAKR) toward t‐butyl 6‐chloro (5S)‐hydroxy‐3‐oxohexanoate ((5S)‐CHOH) were improved by mutating its residues in the loop regions around the substrate‐binding pocket. And the thermostability of KdAKR was improved by a consensus sequence method targeted on the flexible regions. The best mutant M6 (Y28A/L58I/I63L/G223P/Y296W/W297H) exhibited a 67‐fold higher catalytic efficiency compared to the wild‐type (WT) KdAKR, and improved R‐selectivity toward (5S)‐CHOH (dep value from 47.6% to >99.5%). Moreover, M6 exhibited a 6.3‐fold increase in half‐life (t1/2) at 40°C compared to WT. Under the optimal conditions, M6 completely converted 200 g/L (5S)‐CHOH to diastereomeric pure t‐butyl 6‐chloro‐(3R, 5S)‐dihydroxyhexanoate ((3R, 5S)‐CDHH) within 8.0 h, with a space‐time yield of 300.7 g/L/day. Our results deepen the understandings of the structure−function relationship of AKRs, providing a certain guidance for the modification of other AKRs.

Purpose To assess the safety and efficacy of intraoperative dexamethasone intravitreal (DEX) implant in patients with diabetic macular edema (DME) undergoing femtosecond laser assisted cataract surgery (FLACS). Methods In this single-center retrospective study, the charts of patients who underwent combined FLACS and DEX implant in the previous three months were reviewed. Primary outcome measures were ocular complications; secondary outcome measures were the change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Results 20 eyes of 20 patients were included. None developed intraoperative or postoperative complications. Mean BCVA was 20/120 (logMAR, 0.78 ± 0.31) at baseline and improved significantly to 20/63 (logMAR, 0.52 ± 0.24; p = 0.01), 20/58 (LogMAR, 0.48 ± 0.28; p < 0.001) and to 20/58 (LogMAR, 0.48 ± 0.31; p < 0.001) at month 1,2 and 3, respectively. A mean improvement of 0.30 LogMAR was recorded at month 1 and 3. Mean CRT decreased significantly from 416.6 ± 76.1 μm at baseline to 322.4 ± 46.4 μm (p < 0.001), to 300.7 ± 29.7 μm (p < 0.001), and to 319.8 ± 54.7 μm (p < 0.001) at month 1,2 and 3, respectively. Comparing to the 1-month follow-up, the largest mean reduction in CRT (112.4 ± 68.9 µm) was observed at month 2 (p = 0.001). Fourteen patients (70%) had an improvement of CRT over the first 2 months followed by a recurrence of edema at month 3. Conclusion DEX implant following FLACS seems to be a safe and effective approach for patients with coexisting cataract and DME.

AbstractThe Cryogenic Underground Observatory for Rare Events (CUORE) is the first cryogenic experiment searching for $$0\nu \beta \beta $$ 0 ν β β decay that has been able to reach the one-tonne mass scale. The detector, located at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, consists of an array of 988 $${\mathrm{TeO}}_{2}$$ TeO 2 crystals arranged in a compact cylindrical structure of 19 towers. CUORE began its first physics data run in 2017 at a base temperature of about 10 mK and in April 2021 released its $$3{\mathrm{rd}}$$ 3 rd result of the search for $$0\nu \beta \beta $$ 0 ν β β , corresponding to a tonne-year of $$\mathrm{TeO}_{2}$$ TeO 2 exposure. This is the largest amount of data ever acquired with a solid state detector and the most sensitive measurement of $$0\nu \beta \beta $$ 0 ν β β decay in $${}^{130}\mathrm{Te}$$ 130 Te ever conducted . We present the current status of CUORE search for $$0\nu \beta \beta $$ 0 ν β β with the updated statistics of one tonne-yr. We finally give an update of the CUORE background model and the measurement of the $${}^{130}\mathrm{Te}$$ 130 Te $$2\nu \beta \beta $$ 2 ν β β decay half-life and decay to excited states of $${}^{130}\mathrm{Xe}$$ 130 Xe , studies performed using an exposure of 300.7 kg yr.

To figure out how polyphenol compounds with a low molecular weight helped in aluminum tannage, a complex of gallic acid and aluminum as well as its application to the tanning of hide powder was studied in this paper. Precipitation points of aluminum chloride solution with different concentrations of gallic acid were measured to guide the basification in hide powder tannage. UV-Visible spectra showed that gallic acid and aluminum would form soluble complexes in aqueous solution and the complexation reaction was pH reliable. Through stoichiometry studies, generations of the 1:2 complex under pH 4.0 and 2:3 complex under pH 4.5 were discovered. Results of stoichiometry studies and Fourier Transform Infrared Spectroscopy (FTIR) spectra confirmed that aluminum-gallic acid complex played the role of links which connected collagen molecules rather than gallic acid or aluminum forming individual bridges with collagen. According to the results of differential scanning calorimetry (DSC) and thermal gravity analysis (TGA), denaturation temperature (Td) of hide powder tanned with different methods, such as aluminum, gallic acid-aluminum combination or aluminum-gallic acid complex, was 76.1°, 82.8° and 85.5°C respectively, and the initial decomposition temperature for the aluminum-gallic acid complex tannage was 300.7°C, also higher than those for another two methods. Furthermore, the results of inductive coupled plasma emission spectroscopy (ICP) showed that after washing for 12 h, the Al2O3 content in hide powder tanned with complex could be maintained at 93.42% of that in unwashed samples, which was the highest among three tanning methods.

Saracatinib/AZD0530 (SAR), a Src tyrosine kinase inhibitor, mitigates seizure-induced brain pathology in epilepsy models upon repeated oral dosing. However, repeated dosing is stressful and can be challenging in some seizing animals. To overcome this issue, we have incorporated SAR-in-Diet and compared serum pharmacokinetics (PK) and brain concentrations with conventional repeated oral dosing. Saracatinib in solution or in-diet was stable at room temperature for &gt;4 weeks (97 ± 1.56%). Adult Sprague Dawley rats on SAR-in-Diet consumed ~1.7 g/day less compared to regular diet (16.82 ± 0.6 vs. 18.50 ± 0.5 g/day), but the weight gain/day was unaffected (2.63 ± 0.5 g/day vs. 2.83 ± 0.2 g/day). Importantly, we achieved the anticipated SAR dose range from 2.5–18.7 mg/kg of rat in response to varying concentrations of SAR-in-Diet from 54 to 260 ppm of feed, respectively. There was a strong and significant correlation between SAR-in-Diet dose (mg/kg) and serum saracatinib concentrations (ng/ml). Serum concentrations also did not vary significantly between SAR-in-Diet and repeated oral dosing. The hippocampal saracatinib concentrations derived from SAR-in-Diet treatment were higher than those derived after repeated oral dosing (day 3, 546.8 ± 219.7 ng/g vs. 238.6 ± 143 ng/g; day 7, 300.7 ± 43.4 ng/g vs. 271.1 ± 62.33 ng/g). Saracatinib stability at room temperature and high serum and hippocampal concentrations in animals fed on SAR-in-Diet are useful to titer the saracatinib dose for future animal disease models. Overall, test drugs in the diet is an experimental approach that addresses issues related to handling stress-induced variables in animal experiments.

Compliance mismatch between the artificial blood vessel and the host vessel leads to abnormal hemodynamics and is a major mechanical trigger of intimal hyperplasia. Efforts have been made to achieve higher compliance of artificial blood vessels. However, the preparation of artificial blood vessels with compliance matching to host vessels has not been realized. A bi-layered artificial blood vessel was successfully prepared by dip-coating and electrospinning composite method using poly(L-Lactide-co-caprolactone) (PLCL) and thermoplastic poly(ether urethane) (TPU). In the case of a certain wall thickness (200 μm), thickness ratios of the PLCL inner layer (dip-coating method) and TPU outer layer (electrospinning method) were controlled at 0:1, 1:9, 3:7, 5:5, 7:3, and 1:0 respectively and the compliance, radial tensile properties, burst pressure, and suture retention strength were investigated. Results showed compliance value of the artificial blood vessel decreased with the increase of the thickness ratio, which suggested the compliance of the bi-layered artificial blood vessel can be regulated by adjusting the ratio of the inner and outer layer thicknesses. In the six different artificial blood vessels, the one with thickness ratio of 1:9 not only had high compliance (8.768 ± 0.393%/100 mmHg) but also can guarantee the other mechanical properties, such as the radial breaking strength (6.333 ± 0.689 N/mm), burst pressure (534.473 ± 20.899 mmHg), and suture retention strength (300.773 ± 9.351 cN). The proposed artificial blood vessel preparation method is expected to achieve compliance matching with the host vessel. It is beneficial for eliminating abnormal hemodynamics and reducing intimal hyperplasia.

Aim To evaluate the incidence of ocular adverse events after loading phase of the brolucizumab therapy in patients with neovascular age-related macular degeneration (nAMD) in real-life clinical practice – in treatment-naive patients and in patients after switching from another anti-VEGF agent. Another aim was to evaluate treatment outcomes in patients with adverse events. Methods This is a multicentre, retrospective, observational study from 16 application centres in the Czech Republic. Patients diagnosed with nAMD were treated with brolucizumab in a fixed regimen of loading phase (3 injections administered at one-month intervals) and the mean follow-up period was 120 ± 10 days after the first injection. The incidence of adverse events and the development of best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with complications were evaluated. A total of 1,098 eyes were followed up, of which 783 were treatment-naive and 315 eyes were after switching from another anti-VEGF agent. Results Adverse events were recorded in 42 eyes (3.83%), of which 30 eyes were treatment-naive (2.7%) and 12 eyes were post-switch (1.09%). The mean baseline BCVA ± SD was 56.7 ± 10.7 ETDRS chart letters in the group of patients with adverse events, 58.8 ± 10.1 letters in treatment-naive patients, and 51.4 ± 10.2 letters in patients after switch from another anti-VEGF agent. The mean baseline CRT ± SD was 432.2 ± 154.7 μm, being 435.8 ± 137.3 μm in treatment-naive patients and 424.5 ± 186.6 μm in patients after switch from another anti-VEGF agent. At the end of the follow-up, the mean BCVA ± SD was 53.4 ± 9.5 ETDRS charts letters in patients with adverse events, 55.6 ± 10 letters in treatment-naive patients, and 47.6 ± 10 letters in patients after switching from another anti-VEGF agent. The mean CRT ± SD at the end of the follow-up was 300.7 ± 115.7 μm in the total patient cohort, 285.2 ± 78.8 μm in treatment-naive patients and 334.5 ± 165.4 μm in patients after switching from another anti-VEGF agent. Conclusion We observed the development of adverse events in the form of intraocular inflammation or vasculitis with subsequent decrease in BCVA in 3.83% of cases after loading phase of the brolucizumab therapy. The decrease in BCVA was reversible in most cases after initiation of anti-inflammatory steroid treatment. From a functional and morphological point of view, we did not demonstrate any statistically significant difference between the groups of treatment-naive patients and patients after switching from another anti-VEGF agent.

Identification of suitable varieties of cow- The soil was red acidic in reaction, me- pea [I/igrza unguiculata (L.) Walp.] for fod: dium in organic carbon (0.69%) and avail- der purpose and their nutritional require- able N (300 kglha), low in available P(6.2 ments specially of phosphorus is important kglha) and rich in available K (295 kgtha). for obtaining higher forage yields under There was a long drought ~~ell(33.8 mi,,- rainfed conditions. heref fore an attempt in 7 rainy days) from mid-June to mid-sep< was made to evaluate the comparative per- tember. The crop was sown on 18 Septem- formance of 4 cowpea varieties (IFC 8401, ber 199 1. A basal dose of 20 kg Nlha and IFC 8503, UPC 8801) and EC 4216) 20 kg K,O/ha was applied along with P as under 3 levels of phosphorus (0, 30 and 60 per treatment. The crop was harvested at kg P,O,/ha) at Tiptur. The experiment was 50% flowering stage which took 65 days conducted during the rainy season (khar~j) from sowing. A rainfall of 288 mm was re- 1991. ceived in 15 rainy days during the crop- growth period. Table 1. Growth parameters, green-fbcjder and dry mat- The plant height and number of leaves/ ter yields of cowpea varieties &q influenced by plant were not affected due to varieties and phosphorus phosphorus (Table 1). Green-fodder yields Treatment Plant Trifoliate Yield (qha) of IFC 8503 and IFC 8401 were signifi- he~ght lcavesl (cm) plant Green Dry cantly higher (9.7 and 16.4%, respectively) -- - fodder matter than EC 4216, while all these were at par Variety with UPC 8801. IFC 840 1 122.8 16.2 332.2 The dry-matter yield of IFC 8503 was IFC 8503 116.5 15.0 313.4 significantly higher than that of IFC 8401 UPC 8801 114.7 16.3 308.5 and EC 4216. There was a significant im- EC 4216 118.1 20.5 285.6 provement in dry-matter yield at 60 kg CD (P= 0.05) NS NS 26.9 P,O,/ha compared with the control. On pcr day production basis, the varieties IFC p,o, (kg/ha) 8503 and UPC 8801 performed better (a 0 113.1 15.3 300.7 mean yield of 493 kg green fodder or 59.3 30 120.4 18.5 317.4 kg dry matterlha) than EC 4216 cowpea. 60 120.5 17.2 311.7 A dose of 30 kg P,O,/ha is needed for fod- . CD(P = 0.05) NS NS NS der cowpea crop to obtain higher fodder yields.

Introduction: We present a case report of posterior reversible leukoencephalopathy syndrome (PRES) following transarterial chemoembolization (TACE) of liver metastasis of an intestinal neuroendocrine tumour.Case presentation: A 62-year-old female was evaluated for progressive bilateral vision loss following transarterial chemoembolization (TACE) of hepatic metastasis of a midgut carcinoid tumour with cisplatin. Vital signs were remarkable for significant hypertension (170-210/85-110) since having undergone TACE (baseline BP 136/74), despite pre-procedure administration of octreotide. Blood pressure failed to correct with administration of amlodipine, hydralazine, captopril and labetalol infusion but responded promptly to octreotide infusion. Magnetic resonance imaging showed findings compatible with PRES. The patient’s vision gradually corrected to her baseline over 2 days. Conclusion: TACE for neuroendocrine tumours can be complicated by carcinoid crisis despite pre-administration of octreotide. Rarely, this may present as a hypertensive emergency of which PRES is a manifestation. Prompt recognition and treatment with high dose octreotide are important and can avoid permanent neurological injury in patients.RésuméIntroduction : Il s’agit d’une étude de cas de syndrome de leuco encéphalopathie réversible postérieure (SERP) consécutive à la chimioembolisation transartérielle (CETA) d’une métastase hépatique d’une tumeur neuro-endocrinine intestinale.Présentation du dossier: Une femme de 62 ans est évaluée pour une perte de vision bilatérale progressive à la suite de la chimioembolisation transartérielle (CETA) de métastases hépatiques d’une tumeur du tube digestif effectuée au moyen du cisplatine. Les signes vitaux sont remarquables malgré une hypertension importante (170-210/85-110) depuis la CETA (p.a. de base 136/74) et l’administration d’octréotide préalable à l’intervention. La pression artérielle ne s’est pas corrigée avec l’administration d’amlodipine, d’hydralazine, de captopril et de labétalol en perfusion, mais a répondu promptement à l’octréotide en perfusion. Une imagerie par résonnance magnétique a fourni des résultats compatibles avec un diagnostic de SERP. La vision de la patiente s’est graduellement corrigée pour revenir à son état habituel en deux jours.Conclusion : Dans le cas de tumeurs neuro-endocriniennes, la CETA peut être compliquée d’une crise carcinoïde malgré l’administration d’octréotide au préalable. Cette condition peut, quoique rarement, représenter une urgence hypertensive dont le SERP est une manifestation. L’identification rapide de la condition et un traitement à l’aide d’octréotide à dose élevée sont de la plus haute importance et peuvent éviter des dommages neurologiques permanents.Carcinoid syndrome is a syndrome classically consisting of diarrhea, paroxysms of cutaneous flushing with or without hypotension and bronchospasm arising most frequently in the setting of hepatic metastases originating from midgut carcinoid tumours. However, these neuroendocrine tumours can synthesize a wide variety of polypeptides, prostaglandins, and biogenic amines and hence present atypical clinical manifestations such as pellagra, abdominal pain, right-sided heart failure from valvular lesions and paroxysmal hypertension. Tumour manipulation may result in a massive influx of hormones into the systemic vasculature, potentially resulting in life threatening swings in blood pressure, cardiac arrhythmias and bronchoconstriction, even in patients without liver metastases or preoperative carcinoid syndrome.1 We present a case report of hypertensive emergency presenting as posterior reversible leukoencephalopathy syndrome (PRES) after transarterial chemoembolization (TACE) of a hepatic metastasis of carcinoid tumour.Case PresentationA 62-year-old caucasian female was evaluated on the surgical ward for progressive bilateral vision loss about 10 hours following transarterial chemoembolization (TACE) of a hepatic metastasis of a midgut carcinoid tumour (Figure 1, Figure 2) with Lipiodol and cisplatin. Premedication with octreotide 100 mcg subcutaneously and dexamethasone 8 mg IV pre-procedure was given, and post-procedure orders were given for dexamethasone 4 mg bid, ondansetron as needed and D5% NaCl 0.45% at a rate of 150 mL/h. The rest of her past medical history was unremarkable, specifically without history of hypertension, cerebrovascular disease, or clinical manifestations of carcinoid syndrome prior to admission. She had undergone two intra-abdominal surgeries without complication. Her usual medication was limited to inhaled glycopyrronium and indacaterol. Figure 1. Axial computed tomography scan of hepatic metastasis. A mass is visible in hepatic parenchyma corresponding to a metastasis of the midgut carcinoid tumour. Figure 2. Fluroscopic image of transarterial chemoembolization of hepatic metastasis. Upon evaluation, the patient was somnolent but otherwise well oriented. Eye exam confirmed bilateral 0/20 vision though pupils were 4 mm and reactive. On motor exam, the patient had diffuse hyperreflexia with upgoing plantar reflexes but without focal weakness. Chart review was remarkable for blood pressures ranging from 170-210/85-110 since TACE (pre-procedure blood pressure 136/74). A presumptive diagnosis of PRES due to cisplatin was made.Initial cerebral computed tomography scan was suspicious for a right occipital sub-cortical hypodensity of 3 cm, possibly of ischemic nature. IV fluids were discontinued (NaCl 0.9% at a rate of 250 mL/h) and anti-hypertensive agents were begun. After failure of improvement of blood pressure or symptoms despite amlodipine, hydralazine, labetalol, and captopril, a diagnosis of carcinoid crisis was suspected and octreotide 300mcg IV bolus followed by an infusion of 50 mcg/h was started. The suspected diagnosis of carcinoid crisis was later confirmed by 24h urinary 5-HIAA dosing at 141.4 umol/day (normal 0–42, previously within normal limits pre-operatively). Serum chromogranin A was also elevated at 138.2 ug/L (normal 0–82), compatible with a neuroendocrine tumour.Characteristic changes of PRES were seen on cerebral magnetic resonance imaging (MRI) (Figure 3) including predominantly sub-cortical hyperintensities in the bilateral parietal and occipital lobes on T2 and FLAIR sequences which were also hyperintense on diffusion-weighted imaging (DWI), likely from T2 shine through, and apparent diffusion coefficient (ADC) maps without restricted diffusion, hence confirming the finding of vasogenic edema compatible with PRES. Figure 3. FLAIR sequence, axial slice, cerebral magnetic resonance imaging. Subcortical hyperintensies in the bilateral occipital lobes reflecting vasogenic edema of the visual white matter tracts are seen. The patient’s blood pressure and her visual symptoms progressively normalized over 48 hours. On last follow-up 1 month after procedure, vital signs were normal (blood pressure 115/54) and vision was normal.DiscussionCarcinoid tumours are classically described as slow growing, mainly affecting the gastrointestinal (GI) tract. They are known to internists mainly for their capability to produce the carcinoid syndrome. However, only about 25% of carcinoids actually produce the mediators which produce the carcinoid syndrome and less than 10% of patients actually develop the carcinoid syndrome.2 The syndrome usually presents when midgut carcinoids metastasize to the liver, hence bypassing hepatic metabolism. Typical symptoms include secretory diarrhea (80%) and flushing of the head, neck, and upper torso (90%) which may be associated with hypotension and tachycardia. Less frequent manifestations are right heart failure due to carcinoid valve disease (30%), bronchospasm (15%) and pellagra (5%). 3 The classic triad of flushing, diarrhea and wheezing is infrequently found. Foregut (e.g., bronchial) and extra-digestive midgut (e.g., ovarian) bypass the liver and may result carcinoid syndrome without hepatic metastasis, although symptoms are usually atypical in these cases.Perioperative carcinoid crisis occurs in 10–30% of patients undergoing operative resection. Absence of preoperative carcinoid syndrome decreases the risk of carcinoid crisis, however it may still occur.1 This has led to the recommendation by some that patients be premedicated with somatostatin analogues to block bioactive peptide release and action, with or without other hormone antagonists (e.g., anti-histamines).3 However, the benefit of octreotide prophylaxis has been questioned by other studies.1 Once a carcinoid crisis has occurred, bolus doses of 25–500 mcg and intravenous infusions at rates of 50–150 mcg/h have been effective in case reports and case series, with higher doses being potentially required in patients on maintenance octreotide therapy or with carcinoid heart disease.4Despite a lack of data comparing it to surgical management, transarterial chemoembolization (TACE).5 is a frequent management strategy for patients with liver metastases, especially when patients present with hormonal symptoms and multiple metastases preclude resection. Rates of complication from TACE are difficult to estimate ranging from 0 to 100%, likely due to variable definitions and reporting. Only one study reported on the incidence of post embolization carcinoid crisis,6 with 2 of 12 patients developing the complication. Both had a history of carcinoid syndrome and had been premedicated with octreotide 200 mcg SC before procedure and q8h afterward. One group7 did report a patient who developed transient cortical blindness following TACE which possibly could have been due to PRES.PRES is a syndrome of failure of cerebral blood pressure autoregulation with acute onset elevations of blood pressure from baseline and a combination of altered level of consciousness, visual symptoms, headache and seizures.8 Blood pressure is often only moderately elevated, though significantly above the patient’s baseline. Etiologies are varied but include cytotoxic chemotherapy, eclampsia and other causes of hypertensive emergency. It was originally felt that the patient’s PRES was due to the cisplatin received during TACE with contribution from dexamethasone and iatrogenic fluid overload (NaCl 0.9% at 150 mL/h had been running for several hours) as she had no history of carcinoid syndrome, had been premedicated and had no other findings associated with the disease. However, her lack of response to standard anti-hypertensives and prompt response to octreotide suggest carcinoid crisis as the cause.Neuroimaging with MRI confirms the diagnosis. Findings are compatible with symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parieto-occipital regions. The cortex, basal ganglia, brainstem, and cerebellar may also be involved though less so than the subcortical white matter, while anterior cortical involvement is seen only with the most severe cases. Importantly, the distribution is not confined to a single vascular territory. Classically lesions appear as punctate or confluent areas of hyperintensity on T2 and FLAIR sequences.9 DWI usually shows hypo or iso-intense signal (though sometimes mildly hyperintense from T2 shine through) while ADC maps show increased signal, thus distinguishing PRES from ischemic stroke. With prompt recognition and management, full recovery over a period of days to weeks can be expected. ConclusionsCarcinoid crisis is a well-known and dreaded complication of surgical manipulation of carcinoid tumours. Transarterial chemoembolization of these tumours may also result in carcinoid crisis and our report suggests that pre-procedure carcinoid syndrome is not a prerequisite for this. Presentation may be atypical, as it was in our patient, and so clinical suspicion should be high. When suspected, prompt management with octreotide and other supportive therapies should be instituted.Key Points1. Patients undergoing transarterial chemoembolization for carcinoid tumour metastases are at risk for carcinoid crisis, even if they have been premedicated with octreotide and have no history of carcinoid syndrome.2. Carcinoid crisis may present as hypertensive crisis rather than hypotension, and may give rise to PRES.References1. Condron ME, Pommier SJ, Pommier RF. Continuous infusion of octreotide combined with perioperative octreotide bolus does not prevent intraoperative carcinoid crisis. Surgery 2016;159:358–67.2. Van Der Lely AJ, Herder WWd. Carcinoid syndrome: diagnosis and medical management. Arquivos Brasileiros de Endocrinologia & Metabologia 2005;49:850–60.3. Mancuso K, Kaye AD, Boudreaux JP, et al. Carcinoid syndrome and perioperative anesthetic considerations. J Clin Anesth 2011;23:329–41.4. Seymour N, Sawh SC. Mega-dose intravenous octreotide for the treatment of carcinoid crisis: a systematic review. Can J Anesth/J can d'anesthés2013;60:492–9.5. 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