Phenylpropanoid metabolism enzyme activities and gene expression in postharvest melons inoculated with Alternaria alternata

This study explored the mechanism of melon resistance to Alternaria alternata (A. alternata) infection in Jiashi and 86-1 melons. Melons were inoculated with A.alternata and the change in lesion diameter was measured. The changes in cinnamic acid-4-hydroxylase (C4H), phenylalanine ammonia lyase (PAL), and 4-coumaric acid coenzyme A ligase (4CL) activity and gene expression were studied in the pericarp tissues of Jiashi and 86-1 melons. The lesion diameter was smaller in Jiashi melon than in 86-1 melon, and the pericarp lesions were smaller than pulp lesions, indicating that Jiashi melon can resist A. alternata infection better than 86-1 melon. After inoculation with A. alternata, the C4H, PAL, and 4CL activities of Jiashi and 86-1 melons peaked in the middle and late storage period, and the peak was higher in Jiashi melons. The gene expression changes were consistent with the enzyme activity. The C4H, PAL, and 4CL gene expression was significantly higher in Jiashi melon pericarp than in 86-1 melon, and the C4H, PAL, and 4CL activities in Jiashi melon were positively correlated with their gene expression, confirming the role of phenylpropanoid metabolism enzymes in resistance to A. alternata.

Production of Alternaria Toxins in Yellow Peach (Amygdalus persica) upon Artificial Inoculation with Alternaria alternate

The yellow peach (Amygdalus persica), an important fruit in China, is highly susceptible to infection by Alternaria sp., leading to potential health risks and economic losses. In the current study, firstly, yellow peaches were artificially inoculated with Alternaria alternate. Then, the fruits were stored at 4 °C and 28 °C to simulate the current storage conditions that consumers use, and the Alternaria toxins (ATs) contents from different parts of the fruits were analyzed via ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that the growth of A. alternate and the ATs production were dramatically affected by the storage temperature. At 28 °C, the fungi grew rapidly and the lesion diameter reached about 4.0 cm within 15 days of inoculation, while, at 4 °C, the fungal growth was noticeably inhibited, with no significant change in the lesion diameter. To our surprise, high contents of ATs were produced under both storage conditions even though the fungal growth was suppressed. With an increase in the incubation time, the amounts of ATs showed a steady tendency to increase in most cases. Remarkably, alternariol monomethyl ether (AME), alternariol (AOH), and tenuazonic acid (TeA) were detected in the rotten tissue and also in the surrounding tissue, while a large amount of TeA could also be found in the healthy tissue. To the best of our knowledge, this is the first report regarding the production of ATs by the infection of Alternaria sp. in yellow peach fruits via artificial inoculation under regulated conditions, and, based on the evidence herein, it is recommended that ATs be included in monitoring and control programs of yellow peach management and food safety administration.

Thermal and electric Characteristics of High-power Short-duration Radiofrequency Ablation and Standard Radiofrequency Ablation: A Computer Simulation Study

Background: High power-short duration ablation is an emerging conception for cardiac RF treatment. But the biophysical ablation properties of this technique have not been fully explored. This study compared the electric field characteristics and thermal lesion dimension in High power-short duration (HP-SD) radio frequency (RF) ablation and standard RF ablation by using the finite element method. Results: The results demonstrated that the lesion size and temperature in HP–SD RF ablation increased faster than standard RF ablation. The thermal lesion volume in both ablation modes demonstrated a linear increase and the rate of increase of HP–SD RF ablation grew faster than that of standard RF ablation. For HP–SD application at 50 W for 5 s, the lesion depth was shallower (1.74 to 2.1 mm vs 2.40 to 3.15 mm) and the surface lesion diameter was broader (2.76 to 3.32 mm vs 2.42 to 2.66 mm) than that for standard RF ablation at 25 W for 30 s. Conclusion: Compared with standard RF ablation, HP–SD RF ablation creates a broader lesion width and surface lesion diameter but shallower lesion depth, with a faster increase in temperature. HP–SD ablation is more able to achieve uniform and contiguous lesion shape, which is a suitable for point-to-point RF ablation procedures.Higher temperature was formed in deeper space of cardiac tissue in HP–SD ablation. The duration of HP–SD ablation should be strictly controlled for preventing the steam occur in tissue.

Acute effects of laser myocardial ablation in ex vivo and in vivo

Aim. To study and compare the lesions characteristics of laser energy in heart ex vivo and in experimental large animals.Materials and methods. For the ex vivo experiment a pig heart was obtained from a local slaughterhouse. Laser applications were applied using power 15-30 W in the left and right ventricles 5-50 seconds in duration. Immediately after ablation, examination was performed to determine myocardial damage characteristics at each point. In the experimental study, 7 sheep were included, laser applications were performed under fluoroscopic control in the right atrium with power 10, 15 and 20 W, 10-25 s; in the right ventricle 20, 25 and 30 W for 10-40 s; and in the left ventricle 20, 25 and 30 W for 20-40 s. The animals were euthanized and macroscopic examination of laser lesions was performed.Results. A total of 27 laser applications were performed on the heart ex vivo, all lesions were visualized as white spots on the endocardial surface. The maximum lesion depth was 9 mm achieved when using 20 W /50 s, the maximum lesion diameter was 6 mm, when using 25 W /40 s. The minimum lesion diameter and depth were observed when using 30 W /5 s, 2x1 mm. A total of 48 laser applications were performed in experimental animals, in one experimental animal was observed a transmural lesion in the right atrium when using 15 W /20 s. In 3 out of 7 experimental animals, transmural lesions were observed in the right ventricle when using 20 W /30 s; 20 W /40 s and 30 W /10 s. In the left ventricle, transmural lesions were observed in 2 animals, using 15 W /20 s and 20 W /40 s. In the ex vivo study, there was a strong positive correlation between ablation energy and lesion depth (R=0.91, P<0.05) and lesion volume (R=0.73, P<0.05); while there was no such statistical correlation in vivo.Conclusions. Laser ablation 15-20 W for 15-40 s seems to be optimal for achieving the deepest lesions in the atrium and ventricular myocardium. In our small pilot study with fiberoptic catheter ablation on a beating heart there was no correlation between energy delivered and the depth and volume of necrotic myocardium.

Topical NAVS naphthalan for the treatment of oral lichen planus and recurrent aphthous stomatitis: A double blind, randomized, parallel group study

Aim To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS. Methods The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14). Results No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found. Conclusion No evidence of differences between the two compared interventions was found. Registration Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4.

Development parameters of the latent period as a response of rubber tree resistance to South American leaf blight

ABSTRACT The major phytosanitary problem for rubber tree cultivation in Brazil is the disease known as South American leaf blight, caused by the fungus Microcyclus ulei. Its symptoms manifest in young leaves and cause intense defoliation, resulting in reduced latex production and even the death of susceptible plants. Thus, this disease consists in a constant threat to East Asian plantations. As worldwide traditional breeding programs have evolved, interspecific hybrid clones have currently been used for planting. They are more productive and show better resistance to pathogens. However, traditional breeding programs have not led to significant progress in resistance to South American leaf blight since the selection is directed to clones with complete resistance. In this pathosystem, horizontal or partial resistance (HR) and vertical or complete resistance (VR) can act simultaneously, evidencing their complexity and difficult quantification. This study aimed to: characterize the foliar lesion type in Hevea sp. X M. ulei pathosystem; verify the clonal susceptibility to pathogens; analyze the infection frequency for resistance quantification in Hevea sp. x M. ulei pathosystem, and recommend differentiating rubber tree clones to quantify M. ulei races in Brazil. The monocyclic parameters (latent period and lesion diameter) are applicable for resistance quantification in Hevea sp. x M. ulei pathosystem. Latent period had slight variation among clones. Lesion diameter had wide variation among clones and was a discriminating parameter for horizontal resistance and vertical resistance.

Phase II/III study of SM-88 in patients with metastatic pancreatic cancer.

437 Background: SM-88 (racemetyrosine, Tyme Inc) is a dysfunctional tyrosine derivative used with MPS (methoxsalen 10mg, phenytoin 50mg and sirolimus 0.5mg). SM-88 was well tolerated with improvement in survival among select heavily pretreated PDAC patients who achieved stable disease (HR 0.08, p = 0.02) (Noel et al. Annal Oncol 2019). Circulating tumor cells (CTCs) were prognostic in identifying a PDAC subgroup that may be more likely to benefit from SM-88. Preliminary radiomic analysis of the largest metastases at baseline correlated with baseline CTCs (Ocean et al, Annal Oncol 2019). Here we describe the subsequent randomized portion of the trial in third-line patients only, of SM-88 vs physician/patient choice chemotherapy, to evaluate the potential role of SM-88 in metastatic PDAC through analysis of CTCs and passively acquired biometrics data from a wearable device. Methods:Prospective open-label RCT (Tyme 88 Panc Part 2, NCT03512756) after 2 prior lines for metastatic PDAC. A cell adhesion matrix (CAM) was used to enrich solitary CTCs and cells in clusters floating in the medium after 24 hour culture. Isolated CTCs were collected each cycle on day 1, isolated, and enumerated by flow cytometry using the epithelial cell surface marker Epi+ and cellular uptake of green fluorescent labeled CAM (GCAM+). Results:As of Sept 15, 67 subjects were consented. Randomized and evaluable subjects (n=38) included: mean age 65y (45-86); BMI 24.6 (18.8-38.7); female 39.5%; White 76.3%. Of treated subjects 65.8% (25/38) had 166 AEs, with 25.7% (26/101) being at least possibly SM-88-related, with 1 Grade 3. Four CTC subpopulations defined by GCAM, Epi+ and cluster status, were enumerated and correlated to each other (r=0.03-0.71). At least one CTC subpopulation was detected at baseline (mean 33.8 cells/2mL) in all subjects (n=27). The longest metastatic lesion diameter at baseline correlated with baseline CTCs (r=0.55 for Epi+ cluster; r=0.52 for GCAM+ cluster). CTCs were successfully separated and enumerated at each cycle for correlation with survival, response and other parameters. The median baseline daily step count during the first two weeks on treatment was 3993.8 (IQR: 2745.6 - 5078) for those alive vs. 689.3 (IQR: 630.0-2083.6) among deaths in evaluable subjects (p = NS). Passively acquired mean heart rate during week 3 on trial was 89.3 (SD 10.5) among those who died vs. 78.0 (SD 9.2) among those living; medians are 87.0 for deaths vs. 79.2 for alive (p= NS). Conclusions: In a preliminary exploratory analysis, passively acquired biometrics from a wearable device can be collected for correlation with other clinical outcomes. CTC collection and enumeration is also feasible for correlation with traditional trial outcomes. Given that the longest lesion diameter is correlated with CTCs at baseline, additional radiologic feature analysis (eg radiomics) may be important predictor of CTCs. SM-88 was well tolerated with no treatment-related Grade 4 or 5 events. Clinical trial information: NCT03512756.

Analysis of Risk Factors Related to Complications of Puncture Biopsy in Lung Cancer Patients Under Image Guidance

To investigate the risk factors of complications in lung cancer patients after CT image-guided percutaneous lung biopsy (PTNB), in this study, 110 patients admitted to Xixi Hospital from January 30, 2017 to June 30, 2019 were selected for PTNB, and the basic characteristic information, lesion diameter, number of needle penetration, depth of needle penetration, physiological results of biopsy, postoperative concurrent symptoms, and success rate of biopsy were recorded. In addition, multivariate Logistic regression model (MLRM) was adopted to explore the correlation between various correlated characters and concurrent symptoms. The results showed that the biopsy pathological results were 53 cases of adenocarcinoma, 31 patients with squamous cell carcinoma, 8 patients with thymic carcinoma, 7 patients with small cell carcinoma and 11 patients with lymph carcinoma, and the success rate of needle biopsy was 100% by comparison with the final diagnosis. Among them, 35 patients developed pneumothorax symptoms postoperatively with a complication rate of 31.82%, 22 patients developed hemoptysis postoperatively with a complication rate of 20%, and 6 patients developed infection with a complication rate of 5.45%. The results of regression analysis showed that pneumothorax and hemoptysis were positively correlated with the number of de needles (P < 0.05), and negatively correlated with lesion diameter (P < 0.05). In addition, pneumothorax was also significantly positively correlated with age (P < 0.05), and infection was significantly positively correlated with the number of puncture needles (P < 0.05). Therefore, the main complications after PTNB are pneumothorax and hemoptysis, the high risk factors associated with pneumothorax include lesion diameter, number of puncture needles and age, the high risk factors associated with hemoptysis include lesion diameter and number of puncture needles, and the risk factors associated with infection are number of puncture needles.

Equivocal PI-RADS Three Lesions on Prostate Magnetic Resonance Imaging: Risk Stratification Strategies to Avoid MRI-Targeted Biopsies

We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging—Reporting and Data System (PI-RADS) 3 index lesions. A total of 292 men (2013–2019) from two referral centers were included. A multivariable logistic regression analysis was performed. The discrimination and clinical utility of the built model was assessed by the area under the receiver operation curve (AUC) and decision curve analysis, respectively. A higher PSA-D and higher age were significantly related to a higher risk of detecting csPCa, while the largest index lesion diameter was not. The discrimination of the model was 0.80 (95% CI 0.73–0.87). When compared to a biopsy-all strategy, decision curve analysis showed a higher net benefit at threshold probabilities of ≥2%. Accepting a missing ≤5% of csPCa diagnoses, a risk-based approach would result in 34% of TBx sessions and 23% of low-risk PCa diagnoses being avoided. In men with PI-RADS 3 index lesions scheduled for first-time TBx, the balance between the number of TBx sessions, the detection of low-risk PCa, and the detection of csPCa does not warrant a biopsy-all strategy. To minimize the risk of missing the diagnosis of csPCa but acknowledging the need of avoiding unnecessary TBx sessions and overdiagnosis, a risk-based approach is advisable.

Clinical value of matrix metalloproteinase-2 and -9 in ultrasound-guided radiofrequency ablation treatment for papillary thyroid carcinoma

Objective This study aimed to investigate serum matrix metalloproteinase (MMP)-2 and MMP-9 levels in patients with papillary thyroid carcinoma (PTC). Methods Forty-one patients with PTC undergoing ultrasound-guided radiofrequency ablation (RFA) and 56 controls were included. Serum MMP-2 and MMP-9 levels were determined by enzyme-linked immunosorbent assay before and after surgery. Potential affecting factors were evaluated by logistic regression analysis. Results Serum MMP-2 and MMP-9 levels were significantly higher in PTC patients compared with controls, and decreased significantly after surgery. According to receiver operating characteristic curve analysis, diagnostic values for preoperative serum MMP-2 and MMP-9 levels were 82.4% and 86.6%. There was no contrast-agent perfusion in the ablation zone in 88.5% of lesions, and enhancement within or at the lesion edge in 11.4%. The volume reduction at 3 months’ follow-up was >40%. Age, microcalcification, irregular shape, and lesion diameter and number were influencing factors for PTC. Age, and lesion diameter and number were independent risk factors, while calcification and morphology were protective factors. Conclusion Serum MMP-2 and MMP-9 levels have important clinical values for the diagnosis and treatment of PTC by RFA. Preoperative serum MMP-2 and MMP-9 levels, combined with other affecting factors, contribute to disease prognosis.