Treatment of gastric varices with cyanoacrylate complicated by systemic embolization.

Acute gastric variceal bleeding is a life-threatening condition that could be effectively treated with endoscopic cyanoacrylate injection diluted with lipiodol. The mixture acts as a tissue adhesive that polymerizes when in contact with blood in a gastric varix. This work reports a patient that presented to the emergency department with upper gastrointestinal bleeding due to acute variceal bleeding, who developed systemic embolization following cyanoacrylate injection therapy. This complication culminated in cerebral, splenic and renal infarctions with a fatal outcome. Systemic embolization is a very rare, but the most severe complication associated with endoscopic cyanoacrylate injection and should be considered in patients undergoing this treatment.

Preclinical Efficacy of Cabazitaxel Loaded Poly(2-alkyl cyanoacrylate) Nanoparticle Variants.

Background: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages. The present study aims at comparing two endotoxin-free PACA NP variants (PEBCA and poly(2-ethylhexyl cyanoacrylate); PEHCA), loaded with CBZ and test whether conjugation with folate would improve their effect. Methods: Cytotoxicity assays and cellular uptake of NPs by flow cytometry were performed in different breast cancer cells. Biodistribution and efficacy studies were performed in PDX models of breast cancer. Tumor associated immune cells were analyzed by multiparametric flow cytometry. Results: In vitro studies showed similar NP-induced cytotoxicity patterns despite difference in early NP internalization. On intravenous injection, the liver cleared the majority of NPs. Efficacy studies in the HBCx39 PDX model demonstrated an enhanced effect of drug-loaded PEBCA variants compared with free drug and PEHCA NPs. Furthermore, the folate conjugated PEBCA variant did not show any enhanced effects compared with the unconjugated counterpart which might be due to unfavorable orientation of folate on the NPs. Finally, analyses of the immune cell populations in tumors revealed that treatment with drug loaded PEBCA variants affected the myeloid cells, especially macrophages, contributing to an inflammatory, immune activated tumor microenvironment. Conclusion: We report for the first time, comparative efficacy of PEBCA and PEHCA NP variants in triple negative breast cancer models and show that CBZ-loaded PEBCA NPs exhibit a combined effect on tumor cells and on the tumor associated myeloid compartment, which may boost the anti-tumor response.

Characterization of the fludioxonil and phenamacril dual resistant mutants of Fusarium graminearum.

Fusarium graminearum is an important fungal pathogen causing Fusarium head blight (FHB) in wheat and other cereal crops worldwide. Due to lack of resistant wheat cultivars, FHB control mainly relies on application of chemical fungicides. Both fludioxonil (a phenylpyrrole compound) and phenamacril (a cyanoacrylate fungicide) have been registered for controlling FHB in China, however, fludioxonil-resistant isolates of F. graminearum have been detected in field. To evaluate the potential risk of dual resistance of F. graminearum to both compounds, fludioxonil and phenamacril dual resistant (DR) mutants of F. graminearum were obtained via fungicide domestication in laboratory. Result showed that resistance of the DR mutants to both fludioxonil and phenamacril were genetically stable after sub-cultured for ten generations or stored at 4 °C for 30 days on fungicide-free PDA. Cross-resistance assay showed that the DR mutants remain sensitive to other groups of fungicides, including carbendazim, tebuconazole, pydiflumetofen, and fluazinam. In addition, the DR mutants exhibited defects in mycelia growth, conidiation, mycotoxin deoxynivalenol (DON) production, and virulence Moreover, the DR mutants displayed increased sensitivity to osmotic stress. Sequencing results showed that amino acid point mutations S217L/T in the myosin I protein is responsible for phenamacril resistance in the DR mutants. Our results indicate that mutations leading to fludioxonil and phenamacril dual resistance could result in fitness cost for F. graminearum. Our results also suggest that the potential risk of F. graminearum developing resistance to both fludioxonil and phenamacril in field could be rather low, which provides scientific guidance in controlling FHB with fludioxonil and phenamacril.

Comparative uptake, translocation and metabolism of phenamacril in crops under hydroponic and soil cultivation conditions.

Many studies investigate the plant uptake and metabolism of xenobiotics by hydroponic experiments, however, plants grown in different conditions (hydroponic vs. soil) may result in different behaviors. To explore the potential differences, a comparative study on the uptake, translocation and metabolism of the fungicide phenamacril in crops (wheat/rice) under hydroponic and soil cultivation conditions was conducted. During 7-14 days of exposure, the translocation factors (TFs) of phenamacril were greatly overestimated in hydroponic-wheat (3.6-5.2) than those in soil-wheat systems (1.1-2.0), with up to 3.3 times of difference between the two cultivation systems, implying it should be cautious to extrapolate the results obtained from hydroponic to field conditions. M-144 was formed in soil pore water (19.1-29.9 µg/L) in soil-wheat systems but not in the hydroponic solution in hydroponics; M-232 was only formed in wheat shoots (89.7-103.0 µg/kg) under soil cultivation conditions, however, it was detected in hydroponic solution (20.1-21.2 µg/L), wheat roots (146.8-166.0 µg/kg), and shoots (239.2-348.1 µg/kg) under hydroponic conditions. The root concentration factors (RCFs) and TFs of phenamacril in rice were up to 2.4 and 3.6 times higher than that in wheat for 28 days of the hydroponic exposure, respectively. These results highlighted that cultivation conditions and plant species could influence the fate of pesticides in crops, which should be considered to better assess the potential accumulation and transformation of pesticides in crops.

Efficacy of cytoreductive radical cystectomy in metastatic urothelial bladder cancer based on site and number of metastases.

BACKGROUND: Recent studies have highlighted the overall survival (OS) benefit of cytoreductive radical cystectomy (CRC) in metastatic bladder cancer (mBCa). Cytoreductive surgery has been established in other urologic cancers. However, the efficacy of CRC and optimal criteria for patient selection in mBCa is unclear. This study investigated the oncologic efficacy of CRC, particularly emphasizing the location and number of metastasis sites as a predictor of survival and treatment response. METHODS: A retrospective analysis of cT2-4N0-3M1 mBCa patients treated with multiagent chemotherapy between 2004 and 2019 was conducted using the National Cancer Database. Patients were classified by additional treatment with CRC or conservative local treatment (CLT), consisting of transurethral resection of bladder tumor, radiation, or no local treatment and propensity score (PS) matched. Kaplan-Meier analysis and multivariate Cox Proportional Hazards model assessed the effect of CRC or CLT on OS within the matched cohort and in four subgroups (1) patients with only distant lymph node (LN) metastasis vs. any organ metastasis, (2) patients with single metastasis vs. multiple metastases. Sensitivity analysis estimated the influence of unmeasured confounders on CRC OS benefit. RESULTS: Propensity matching yielded 247 and 251 patients treated with CRC and CLT, respectively. Median OS in patients who received CRC was greater than that of patients treated with CLT (20.4 months vs. 12.0 months, P < 0.001). CRC was associated with reduced mortality risk in patients with only distant LN metastases (HR = 0.545, P = 0.039), any organ metastasis (HR = 0.421, P < 0.001), and single visceral metastasis (HR = 0.483, P = 0.002). However, CRC did not significantly improve OS in patients with multiple metastases (HR = 0.501, P = 0.064). CONCLUSION: These findings demonstrate an OS benefit of CRC with multiagent chemotherapy and pinpoint multiple visceral metastases as a potential contraindication for CRC. Although limited by the influence of unmeasured confounders, these findings may inform future prospective investigations into CRC.

The Effectiveness of Cyanoacrylates versus Sutures for Mesh Fixation after Lichtenstein Repair (SCyMeLi STUDY) A Systematic Review and Meta-Analyze of Randomized Controlled Trials.

Background: Chronic postoperative inguinal pain (CPIP) is still the most frequent complication after open Lichtenstein repair and any strategy to reduce its incidence and implications is a step forward to better outcomes. Between the means of mesh fixation atraumatic glue fixation has been explored as such possibility. A meta-analysis of randomized controlled trials comparing the performance of cyanoacrylate glue versus sutures fixation was conducted. Methods: the meta-analysis was conducted according to the PRISMA guidelines. Randomized controlled trials (RCTs) published between January 2000 and December 2021 were searched for in MEDLINE, PubMed, Web of Science, and Google Scholars. The quality of RCTs and the potential risk of bias were assessed using MINORS criteria and the Cochrane risk of bias tool. Results: of 269 papers the meta-analysis was performed on 19 RCTs including 3578 patients. In the glue fixation group, the operation was shorter (mean pooled difference 6 minutes; SE = 0.47; 95% CI = - 6.77 - - 4.92; t test = -12.36; p 0.0001) and immediate postoperative pain was lower (2.37% vs 13.3%OR - 0.158; 95% CI = 0.064 0.386; p = 0.0001). There was no difference in terms of chronic pain, recurrence rate and wound events. Conclusion: glue fixation of mesh in elective Lichtenstein repair of inguinal hernia seems to be a valid choice for a painful and safe procedure without increasing risk of recurrence.

Comparison of 2-octyl cyanoacrylate with polyester mesh with standard suture and staples in total knee and hip arthroplasty.

OBJECTIVE: The use of 2-octyl cyanoacrylate with polyester mesh (OCA-M) has become common in total hip and knee arthroplasty (THA, TKA). We aimed to compare the safety and cosmetic outcomes between OCA-M and standard suture techniques and staples, and determine whether OCA-M can safely be used for TKA. METHOD: Inclusion criteria were patients who underwent THA or TKA from January 2010 to October 2011 (Suture group), November 2011 to August 2013 (Staple group), March 2017 to September 2018 (OCA-M group). Exclusion criteria was loss of imaging data. Complications during hospitalisation (early complication) and after discharge (late complication) were compared in groups. Plastic and orthopaedic surgeons performed cosmetic evaluations with the modified Vancouver Scar Scale (VSS) and Likert scale at three and six months postoperatively and compared in groups. RESULTS: A total of 249 arthroplasties (suture group=88 patients; staple group=94 patients; OCA-M group=67 patients) were included in the study. The OCA-M group had a significantly lower early complication rate than the suture group (p=0.015). For THA, the OCA-M group had a significantly lower total complication rate than the suture group (p=0.048). For TKA, there was no significant difference among the three groups. The complication rate in the OCA-M group showed no significant difference between THA/TKA. With regards to the VSS, the OCA-M group was significantly better for cosmetic qualities than the suture group (p=<0.001, p=0.021 at three and six months, respectively). For the Likert scale, the OCA-M group was also significantly better for cosmetic qualities than the suture group and staple group (suture-OCA-M, p=0.003 (three months), p=<0.001 (six months); staple-OCA-M, p=0.027 (three months)). CONCLUSION: In this study, the OCA-M complication rate was low compared to suturing and similar to stapling. Moreover, better cosmetic outcomes were achieved compared to suturing and stapling.

Comparison of Radiofrequency Ablation and Cyanoacrylate Closure for Large-Diameter Great Saphenous Vein Insufficiency.

BACKGROUND: To compare radiofrequency ablation (RFA) and cyanoacrylate closure (CAC) for large-diameter great saphenous vein (GSV) insufficiency between diameters of 12 and 16 mm. METHODS: This study is a single-center retrospective study. Subjects who underwent endovenous treatment with RFA (Group A) or CAC (Group B) for GSV insufficiency between June 2015 and June 2021 who were followed up for at least 2 years were included in the study. Subjects who had a 12-mm to 16-mm target vessel diameter and subjects with grade 3 and grade 4 reflux were included. Subjects' demographic data (age, sex), body mass indices, clinical, etiological, anatomic, pathophysiologic classification, GSV diameter, reflux grade, target vessel length, preoperative venous clinical severity score (VCSS), procedural time, postoperative first-day pain scores, postoperative 14th-day patient satisfaction scale, and postoperative complications were noted. In follow-up, subjects were evaluated with duplex ultrasonography and VCSS at 1, 6, 12, and 24 months. RESULTS: In total, 142 subjects were included (n = 71 for both groups). The mean GSV diameter was 13.21 ± 1.00 for Group A and 13.51 ± 0.97 for Group B. The groups did not differ in terms of age, sex, body mass index, clinical, etiological, anatomic, pathophysiologic classification, GSV diameter, reflux grade, target GSV length, preoperative VCSS, complications, postoperative 24-hr pain status or postoperative 14-day patient satisfaction scale (P > 0.05 for all comparisons). The procedure time was significantly shorter in Group B (34.68 ± 4.22 min for Group A vs. 22.59 ± 4.5 min for Group B, P = 0.001). In the 1-month and 6-month Duplex ultrasonography of the subjects, partial closure and patency rates in Group B were significantly higher than those in Group A (P = 0.003 and P = 0.025, respectively). At the 12-month and 24-month evaluation, closure rates did not show a statistically significant difference between the groups (P = 0.056 and P = 0.090, respectively). Preoperative and 1-month VCSS measurements did not show a statistically significant difference between groups (P > 0.05 for all comparisons). The 6-month, 12-month, and 24-month VCSS measurements of Group A were significantly higher than those in Group B. (P = 0.043, P = 0.009 and P = 0.002, respectively). CONCLUSIONS: Both RFA and CAC were found to be effective in the treatment of large-diameter GSV incompetency. The complication rates were similar between the 2 techniques. CAC had a shorter procedure time. Although the closure rates in the early postoperative period were better in the RFA group, long-term follow-up demonstrated similar patency rates. The functional results in the long-term follow-up were better in the RFA group.

Cyanoacrylate tissue adhesive versus silk sutures for mandibular third molar surgery: a systematic review and meta-analysis.

OBJECTIVE: Cyanoacrylate tissue adhesive has been presented as an alternative to sutures and several studies have compared them. The objective of this meta-analysis was to evaluate the effect of cyanoacrylate tissue adhesive on postoperative pain and swelling, following mandibular third molar surgery. MATERIALS AND METHODS: Database search was conducted in MEDLINE/PubMed and Scopus, along with extensive search in the grey literature, including randomized and non-randomized clinical trials that applied cyanoacrylate adhesive for closing mandibular third molar surgical sites and compared it with silk sutures, assessing postoperative pain and swelling. The search ended on September 22, 2023. RESULTS: Of 886 identified articles, six were included and meta-analyzed. Applying cyanoacrylate demonstrated a reduction in the overall postoperative pain (SMD = -0.57, 95% CI -1.00 to -0.15, p = 0.009). A similar outcome was noted when pain was evaluated on the first and last postoperative days, based on controlled clinical trials (SMD = -0.47, 95% CI -0.92 to -0.03, p = 0.04), and randomized trials (SMD = -0.97, 95% CI -1.31 to -0.62, p < 0.00001). Patients/sides received cyanoacrylate showed a decrease in postoperative swelling (SMD = -0.26, 95% CI -0.51 to -0.01, p = 0.04). Following the GRADE rating system, the quality of evidence on pain and swelling was judged as moderate and low, respectively. CONCLUSIONS: The use of cyanoacrylate adhesive may offer benefit in reducing postoperative pain and swelling following mandibular third molar surgery. Nevertheless, this should be further investigated, considering the low number of included reports. CLINICAL RELEVANCE: The current results could help clinicians who perform this procedure to manage postoperative pain and swelling more effectively.

Effect of 5-Alpha Reductase Inhibitors on Magnetic Resonance Imaging and Prostate Cancer Detection.

Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.

Successful Sealing of Post-COVID-19 Bronchopleural Fistula with Computed Tomography Scan-Guided Percutaneous Cyanoacrylate Glue Injection: A Case Series.

Bronchopleural fistula (BPF), a sinus tract between the bronchial system and the pleural space, is associated with COVID-19 and can lead to pneumothorax, which increases the mortality rate. Due to the analytical status of COVID-19 patients, sealing the BPF necessitates the least minimal invasive treatment. Herein, we demonstrated a technique of sealing post-COVID-19 BPF with direct injection of cyanoacrylate glue under the guidance of a computed tomography scan. Following glue injection, the BPF was completely sealed in all four patients. In conclusion, in COVID-19 patients with small and distal BPF, percutaneous glue injection is recommended for BPF closure.

Hypersensitivity reactions following vein closure therapy with venasealTM (n-butyl- 2-cyanoacrylate).

VenaSealTM is composed of a cyanoacrylate adhesive compound often utilized for chronic venous stasis treatment. Rare case reports of hypersensitivity reactions to this compound exist. We present the first case of dermatographism and angioedema after utilization of VenaSealTM successfully treated via high dose antihistamines. We also present a case of type IV hypersensitivity to VenaSealTM, a cyanoacrylate, occurring in a patient with known meth(acrylate) allergy indicating a possible cross reactivity between these acrylate groups.

Seroma control in axillary lymphadenectomy with Glubran 2® without drain. Multicenter, prospective, randomized, clinical trial. GALA-ND study (Glubran, Axillary Lymphadenectomy, Ambulatory, No Drain).

BACKGROUND: Seroma after breast cancer surgery is a frequent entity; therefore, different products have been described in literature with the aim to reduce it. The most studied ones have been the sealants products, being tested with aspirative drains. Symptomatic seroma represents the 19% after axillary lymphadenectomy without drains. The aim of this study is to analyze the effect of a sealant in the seroma control after axillary lymphadenectomy without drains and identify the risk factors related to symptomatic seroma. METHODS: This is a prospective, multicenter, international, and randomized clinical trial. Patients undergoing conservative surgery and axillary lymphadenectomy for breast cancer will be randomized to control group (lymphadenectomy without sealant) or interventional group (lymphadenectomy with sealant Glubran 2®). In any of the study groups, drains are placed. Patients who received neoadjuvant treatment are included. Measurements of the study outcomes will take place at baseline; at 7, 14, and 30 days post-surgery; and at 6-12 months. The primary outcome is symptomatic seroma. Secondary outcomes are seroma volume, morbidity, quality of life, and lymphedema. DISCUSSION: Several studies compare the use of sealant products in axillary lymphadenectomy but generally with drains. We would like to demonstrate that patients who underwent axillary lymphadenectomy could benefit from an axillary sealant without drains and reduce axillary discomfort while maintaining a good quality of life. Assessing the relationship between axillary volume, symptoms, and related risk factors can be of great help in the control of seroma in patients who received breast cancer surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05280353. Registration date 02 August 2022.

Blocked-flow vs. free-flow cyanoacrylate glue embolization: Histological differences in an in vivo rabbit renal artery model.

PURPOSE: The purpose of this in vivo animal study was to compare the acute histological effects on the arterial vessel wall of free-flow vs. blocked-flow embolization with metacryloxysulfolane-n­butyl cyanoacrylate (MS-NBCA) in several concentrations. MATERIALS AND METHODS: A total of 42 rabbit renal arteries were embolized using MS-NBCA mixed with ethiodized oil. The MS-NBCA concentration was 12.5%, 25%, or 50%. All mixtures were injected under both free-flow and blocked-flow conditions. The rabbits were euthanised 30 min after arterial embolization. Arterial-lumen distension, intimal inflammation and necrosis, peri­arterial edema, and distality of MS-NBCA penetration were assessed histologically. Multivariable regression analyses were performed using a manual backward procedure, with linear, ordinal and logistic regression to search for factors associated with these outcomes RESULTS: Marked or severe dilatation was observed in 36 out of 42 arteries (86%) and marked or transmural intimal arteritis in all 42 arteries (42/42; 100%). Lumen dilatation caused focal vessel-wall flattening, which resulted in intimal necrosis. Multifocal necrosis extending from the intima to the media occurred in 23 out of 42 kidneys (55%) and peri­arterial edema with multifocal vascular leakage in 19 out of 42 kidneys (45%). At multivariable analysis, blocked-flow MS-NBCA injection was associated with greater severity of vessel-wall lesions, including intimal arteritis (P = 0.003) and intimal necrosis (P = 0.014), compared to free-flow injection. Blocked-flow injection was also associated with peri­arterial edema (P = 0.008) and greater distality of MS-NBCA penetration (P = 0.001). CONCLUSION: Blocked-flow MS-NBCA injection during renal artery embolization is significantly associated with more acute arterial-wall damage and greater distality of glue penetration compared to free-flow injection in a rabbit model. These preliminary findings may have clinical implications, as blocked-flow injection is routinely used to treat specific vascular diseases or malformations in human.

Polyethylene glycol (PEG) as a broad applicability marker for LC-MS/MS-based biodistribution analysis of nanomedicines.

Polyethylene glycol (PEG) conjugation (PEGylation) is a well-established strategy to improve the pharmacokinetic and biocompatibility properties of a wide variety of nanomedicines and therapeutic peptides and proteins. This broad use makes PEG an attractive 'allround' candidate marker for the biodistribution of such PEGylated compounds. This paper presents the development of a novel strategy for PEG quantification in biological matrices. The methodology is based on sample hydrolysis which both decomposes the sample matrix and degrades PEGylated analytes to specific molecular fragments more suitable for detection by LC-MS/MS. Method versatility was demonstrated by applying it to a wide variety of PEGylated compounds, including polymeric poly(ethylbutyl cyanoacrylate) (PEBCA) nanoparticles, lipidic nanoparticles (Doxil®, LipImage 815™ and lipid nanoparticles for nucleic acid delivery) and the antibody Cimzia®. Method applicability was assessed by analyzing plasma and tissue samples from a comprehensive drug biodistribution study in rats, of both PEBCA and LipImage 815™ nanoparticles. The results demonstrated the method's utility for biodistribution studies on PEG. Importantly, by using the method described herein in tandem with quantification of nanoparticle payloads, we showed that this approach can provide detailed understanding of various critical aspects of the in vivo behavior of PEGylated nanomedicines, such as drug release and particle stability. Together, the presented results demonstrate the novel method as a robust, versatile and generic approach for biodistribution analysis of PEGylated therapeutics.

Technical note: A preliminary assessment of UV-C imaging using the Full Spectrum Imaging System (FSIS-II) for the detection of latent fingermarks.

The Full Spectrum Imaging System (FSIS-II) was assessed for the detection of latent fingermarks on a variety of substrates, specifically focusing on UV-C imaging for untreated marks and those that have been treated with cyanoacrylate (CA). The use of UV-C was effective at the detection of latent fingermarks on a variety of substrates and UV-C imaging may be effective when UV-A does not provide any fingermark detections on thermal paper. A Phase 2 and a small Phase 3 trials on aluminium cans were carried out with a detection sequence of UV-C imaging, CA fuming, UV-C imaging, UV-A imaging and BY40. For Phase 2 laboratory trials, the use of initial UV-C reflection was effective at removing the background and was a useful tool for initial screening. The use of UV-C was superior to UV-A after CA fuming and provided the highest overall number of high-quality marks. For phase 3 trials, the results showed that BY40 fluorescence was marginally more effective than UV-C imaging of CA-treated marks. This preliminary study shows that the FSIS-II and UV-C imaging can complement other methods for the detection of latent fingermarks.

Analysis of stability for nut yield and ancillary traits in cashew (Anacardium occidentale L.).

Cashew is cultivated in varied agro-ecological regions of India and yield levels vary with regions. Therefore, to identify stable genotype for yield, 18 genotypes were tested in four environments for nut yield and ancillary traits during 2008 to 2018 in randomized block design with two replications. The data of 6th annual harvest and cumulative nut yield of six years was analyzed employing additive main effect and multiplicative interaction (AMMI) and genotype and genotype by environment (GGE) methods. Analysis of variance for 6th annual harvest indicated significant differences (p < 0.01) for eight traits. Environments varied significantly (p < 0.01) for seven traits. Genotype by environment (G × E) interactions were significant (p < 0.01) for all traits. Analysis of variance for cumulative yield revealed significant variations between genotypes, environments, G x E interactions. Interaction principal component analysis (IPCA) 1 (84.39%) and IPCA 2 (10.27%) together captured 95% of variability. Genotypes, environments and G × E interaction were accounted for 16.18%, 4.50% and 77.22% respectively of total variation. The environment Pilicode discriminated better while Vridhachalam was representative. BPP-8 and Vengulra-7 were the winning genotypes in Bhubaneswar while Kanaka and Priyanka in Pilicode, Vengurla-4 in Jhargram and UN-50 in Vridhachalam. Therefore, promoting cultivation of these winning genotypes in the corresponding environments is highly recommended to enhance cashew nut production. As per ASV (AMMI stability value,) K-22-1 was stable genotype followed by Bhubaneswar-1. As per YSI (yield stability index), Bhubaneswar-1 was stable and high yielding followed by K-22-1 and BPP-8. Thus stable genotypes identified in this study viz., K-22-1 and Bhuvaneswar-1 are recommended for cultivation in west and east regions of India which have most cashew growing areas for increasing the cashew nut production.

Characterizing the Molecular Mechanism of the Lethal C423D Mutation in FgMyoI: A Molecular Perspective.

The lethal mutation C423D in Fusarium graminearum myosin I (FgMyoI) occurs close to the binding pocket of the allosteric inhibitor phenamacril and causes severe inhibition on mycelial growth of F. graminearum strain PH-1. Here, based on extensive Gaussian accelerated molecular dynamics simulations and wet experiments, we elucidate the underlying molecular mechanism of the abnormal functioning of the FgMyoIC423D mutant at the atomistic level. Our results suggest that the damaging mutation C423D exhibits a synergistic allosteric inhibition mechanism similar to but more robust than that of phenamacril, including effects on the active site and actin binding. Unlike phenamacril-induced closure of Switch2, the mutation results in unfolding of the N-terminal relay helix with a partially opened Switch2 and blocks the structural rearrangement of the relay/SH1 helices, impairing the proper initiation of the recovery stroke. Due to the significant influence of C423D mutation on the function of FgMyoI, designing covalent inhibitors targeting this site holds tremendous potential.

EUS-Guided Combined Injection Therapy as a Secondary Prophylaxis of Gastric Variceal Bleeding in a Patient Contraindicated for TIPS: Case Report.

Background: Although bleeding from gastric varices is less observed than esophageal variceal bleeding (VB) (25% vs. 64%), it is associated with an exceedingly high mortality rate of up to 45%. Current guidelines suggest that endoscopic cyanoacrylate injection therapy (ECI) is the first-line treatment for gastric variceal bleeding (GVB). A major concern, however, is the possibility of embolic incidents, which are clinically evident in approximately 1% of cases. There are no guidelines for secondary prophylaxis of GVB. Radiological treatments using a transjugular intrahepatic portosystemic shunt (TIPS) or balloon occlusive transvenous obliteration (BRTO) are considered viable. However, they are not universally inapplicable; for instance, in the setting of pulmonary hypertension (TIPS). EUS-guided combined injection therapy (EUS-CIT) (embolization coils + cyanoacrylate) is an emerging procedure with a perceived reduced risk of systemic embolization. Case presentation: A patient with alcoholic liver cirrhosis was subjected to EUS-CIT as a secondary prophylaxis for GVB. He had three VB episodes of prior presentation treated by endoscopic band ligation (EBL) and ECI. Due to recurrent episodes of bleeding, he was referred to TIPS, but was considered contraindicated due to severe pulmonary hypertension. EUS-CIT was conducted with two embolization coils inserted into the varix, followed by an injection of 1.5 mL of cyanoacrylate glue. A 19 Ga needle, 0.035″ 14/70 mm coils, non-diluted n-butyl-caynoacrylate, and a transgastric approach were utilized. There were no immediate complications. Complete obliteration of the GV was observed in a follow-up endoscopy on day 30. Subsequent endoscopies in months three and six showed no progression of gastric varices. Conclusions: Our initial experience with EUS-CIT suggests that it can be successfully used as secondary prophylaxis for recurrent GVB.