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Nearly 80 different viruses belonging to different genera and families have been identified in grapevines, but their seed transmissibility remains largely unclear. Thus, the specific objective of this work is to monitor the presence of viruses in seedlings grown from seeds of virus-infected grapevine plants. Using reverse-transcription polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR, we showed the presence of grapevine leafroll-associated virus 2 (GLRaV-2), GLRaV- 3, grapevine 'Pinot gris' virus (GPGV), grapevine rupestris stem pitting-associated virus (GRSPaV), grapevine virus A (GVA), and grapevine fleck virus (GFkV) in all tested parts including mature cane, leaf, petiole, young shoot, flower, berry skin, and seed of infected grapevine 'Moldova' plants. Furthermore, GLRaV-2 and GPGV were found in all tested seedlings developed from seeds of 'Moldova' plants, while the other four viruses were not detected. Our results provide the first evidence that GLRaV-2 and GPGV can be transmitted to progeny seedlings from seeds of infected grapevine plants. [ABSTRACT FROM AUTHOR]

Efforts to control viral diseases of grapevine include the production of certified material and development of virus‐resistant transgenic grapevines. However, effective antiviral agents, once the viruses have infected the plants, are still lacking. This study shows that a crude garlic extract has significant antiviral activity against grapevine viruses. Replication of grapevine leafroll‐associated virus 2 (GLRaV‐2) was obviously inhibited in grapevine cv. Cabernet Sauvignon calli treated with diluted (1:100) garlic extract. The relative RNA levels of GLRaV‐2 and grapevine fleck virus (GFkV) in cv. Summer Black grapevine in in vitro‐grown plantlets 10 days after treatment with diluted (1:100) garlic extract were about 22% and 20%, respectively, of that in controls. The viral RNA accumulation of GLRaV‐2, GFkV, grapevine virus A (GVA), grapevine fanleaf virus (GFLV) and grapevine rupestris stem pitting‐associated virus (GRSPaV) in field‐grown grapevine cv. Centennial Seedless plants sprayed with diluted (1:100) garlic extract were about 31–40%, 26–38%, 18–31%, 17–42% and 15–18%, respectively, of that in controls. Moreover, the garlic extract treatment led to a significant decrease in viral RNA accumulation of GLRaV‐3, GLRaV‐2, GVA, GFkV, GFLV, GRSPaV and grapevine Pinot Gris virus in pot‐grown grapevine cv. Shine Muscat plants, and viral disease symptoms in these plants were obviously attenuated. In addition, this extract significantly induced expression of pathogenesis‐related protein genes and stimulated activity of antioxidant enzymes in grapevines. Taken together, these results indicate that the crude garlic extract acts as a significant inhibitor against a broad range of grapevine viruses. [ABSTRACT FROM AUTHOR]

The radiative forcing of anthropogenic aerosol remains a key uncertainty in the understanding of climate change. This study quantifies the model spread in aerosol forcing associated with (i) variability internal to the atmosphere and (ii) differences in the model representation of weather. We do so by performing ensembles of atmosphere-only simulations with four state-of-the-art Earth system models, three of which will be used in the sixth coupled model inter-comparison project (CMIP6, Eyring et al., 2016). In those models we reduce the complexity of the anthropogenic aerosol by prescribing the same annually-repeating patterns of the anthropogenic aerosol optical properties and associated effects on the cloud reflectivity. We quantify a comparably small model spread in the long-term averaged ERF compared to the overall possible range in annual ERF estimates associated with model-internal variability. This implies that identifying the true model spread in ERF associated with differences in the representation of meteorological processes and natural aerosol requires averaging over a sufficiently large number of annual estimates. We characterize the model diversity in clouds and use satellite products as benchmarks. Despite major inter-model differences in natural aerosol and clouds, all models show only a small change in the global-mean ERF due to the substantial change in the global anthropogenic aerosol distribution between the mid-1970s and mid-2000s, the ensemble mean ERF being -0.47 Wm-2 for the mid-1970s and -0.51 Wm-2 for the mid-2000s. This result suggests that inter-comparing ERF changes between two periods rather than absolute magnitudes relative to pre-industrial might provide a more stringent test for a model's ability for representing climate evolutions. [ABSTRACT FROM AUTHOR]

The article reports on medical cases of postvaccination syncope in adolescents in the U.S. from January 2005 to July 2007. Analyses were done by the Centers for Disease Control and Prevention and the Food and Drug Administration using data from the Vaccine Adverse Event Reporting System. Details on the number of postvaccination episodes by selected characteristics are presented. Also noted are the four limitations of the analyses.

Objective: To investigate the clinical efficacy and safety analysis of bronchial thermoplasty (BT) in the treatment of severe asthma and asthma-chronic obstructive pulmonary disease overlap. Methods: The clinical data of 49 patients with asthma-COPD overlap who received BT in the University of Chinese Academy of Sciences Shenzhen Hospital from January 2016 to December 2018 and 50 patients with severe asthma who received BT in the same period were retrospectively analyzed. Patients were divided into overlap group and asthma group, and the baseline data of two groups were recorded. The pulmonary function before and after treatment (including forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 ), FEV 1 as a percentage of predicted value (FEV 1 % pred)), hormone consumption, asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score, asthma control questionnaire (ACQ) score, the overlap group before and after treatment COPD assessment test (CAT) score, modified British Medical Research Council (mMRC) score and postoperative respiratory adverse events in the next 3 weeks were comparatively analyzed. Results: The general baseline characteristics of the two groups are compared. The patients in the overlap group were older than those in the asthma group, and the course of disease and smoking history were longer than those in the asthma group. The inhaled hormone dosage in asthma group was greater than those in the overlap group ((64±11) years vs (48±11) years; 10.00 (10.00, 25.00) years vs 9.00 (1.75, 20.00) years; 20.00(2.00, 40.00) years vs 0 (0, 10.00) years; 320 (320, 640) μg/d vs 960 (320, 960) μg/d) (all P <0.05). The predicted values of lung function indexes FVC, FEV 1 , FEV 1 % pred in the overlap group before treatment were all lower than those in the asthma group (1.98 (1.43, 2.43) L vs 2.54 (2.02, 3.15) L; 0.92 (0.61, 1.26) L vs 1.69(1.17, 2.16) L; (50±16) L vs (65±14) L) (all P<0.05). There were no significant differences in ACT, ACQ, and AQLQ scores between the two groups before treatment (all P >0.05). Within 3 months after treatment, except for no significant improvement in FEV 1 % predicted value and inhaled hormone dosage in the overlap group (all P >0.05), other indexes in both groups were improved compared with those before treatment (all P <0.05). After 1 year of treatment, all indexes of the two groups were significantly improved than those before treatment, and all indexes of the asthma group were better than those of the overlap group (all P <0.05). In terms of respiratory adverse events occurring within 3 weeks after the operation, the incidence of cough and bloody sputum in the overlap group was higher than that in the asthma group, while the incidence of sputum and short-term wheezing was lower than that in the asthma group (all P <0.05). There were no statistically significant differences in the incidence of chest tightness, chest pain, segmental atelectasis and pneumonia between the two groups (all P >0.05), and the postoperative adverse reactions could be effectively controlled in a short period of time. Conclusion: BT treatment could not only improve the lung function, clinical symptoms and quality of life of asthmatic patients, but was also effective for asthma-COPD overlap patients. However, BT treatment had more benefits for asthmatic patients without serious adverse events occurred.

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in severe asthma patients with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred) <60%. Methods: A retrospective analysis was performed on 75 patients with asthma who were treated with BT at Shenzhen University Hospital of the Chinese Academy of Sciences from January 2016 to January 2018. The patients were divided into two groups based on the FEV(1)%pred before treatment: FEV(1)%pred <60% group (39 cases) and FEV(1)%pred ≥60% group (36 cases). Comparative analysis of glucocorticoid consumption, times of acute attack, asthma control test (ACT) score, changes in lung function, and adverse reactions at 3 weeks after treatment were performed between the two groups of patients. Results: Before BT treatment, the consumption of oral prednisone, the amount of budesonide inhaled, and the times of acute attack [ M ( Q (1), Q (3))] in the FEV(1)%pred <60% group were significantly greater than those in the FEV(1)%pred ≥60% group, and the ACT score was significantly lower than the FEV(1)%pred ≥60% group [10.00 (0, 20.00) vs 0(0, 3.75) mg/d, 960 (320, 960) vs 320 (320, 640) μg/d, 5(4, 8) vs 4 (4, 5) times/year, 13 (9, 15) vs 17 (13, 19) scores] (all P< 0.05). Except that the oral prednisone dosage in the FEV(1)%pred<60% group was still higher 1 year after treatment [0 (0, 5.00) vs 0 (0, 0) mg/d] ( P= 0.009), there was no significant difference in the remaining indicators between the two groups 1 year after treatment and 2 years after treatment (all P> 0.05). After 1 year and 2 years of treatment, all indicators in the two groups were better than before treatment (all P< 0.05). The inhaled budesonide amount and the times of acute exacerbation in the FEV(1)%pred <60% group 2 years after treatment were less than those 1 year after treatment [320 (320, 320) vs 320 (320, 640) μg/d, 0 (0, 0) vs 0(0, 1) times/year] (all P< 0.05), and there was no significant difference in the remaining indicators. In the FEV(1)%pred ≥60% group, there was no significant difference between 2 years after treatment and 1 year after treatment in the above indicators except the amount of inhaled budesonide (all P> 0.05). In the FEV(1)%pred <60% group, FEV(1) and the FEV(1)%pred were significantly lower than the FEV(1)%pred ≥60% group before treatment, 1 year after treatment and 2 years after treatment [FEV(1):(1.21±0.41) vs (2.26±0.80)L, (1.84±0.73) vs (2.30±0.78)L, (1.70±0.66) vs (2.38±0.76)L; FEV(1)%pred:46.2 (38.5, 53.7)% vs 80.8(66.5, 93.6)%, 60.1 (48.2, 71.6)% vs 87.4 (68.5, 96.5)%, 58.5 (48.6, 74.8)% vs 86.6 (73.0, 97.3)%] (all P< 0.05). In the FEV(1)%pred <60% group, FEV(1) and FEV(1)%pred 1 year after treatment and 2 years after treatment were all increased compared with before treatment (all P< 0.05). In the FEV(1)%pred ≥60% group, there was no statistical difference in FEV(1) at each time point before and after treatment (all P> 0.05), but the FEV(1)%pred at 2 years after treatment was higher than before treatment ( P< 0.05). There were no significant differences in adverse events between the two groups (all P> 0.05). Conclusion: BT can significantly improve the lung function, reduce the times of acute attack and the dosage of glucocorticoids in severe asthma patients with FEV(1)% pred<60%, which is safe and effective.

The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factor-kB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.

Objectives: We aimed to assess the long-term safety and tolerability of imatinib in diffuse cutaneous systemic sclerosis (dcSSc)., Methods: In this open-label, single-arm, extension-phase clinical trial, patients continued imatinib for 24 months following 12 months of initial treatment., Results: Seventeen patients were enrolled. Forty of 92 adverse events (AE) and 0/6 serious (S) AEs were possibly related to medication. The MRSS decreased from a median of 21 to 16, (p=0.002)., Conclusions: This study demonstrates long-term safety and tolerability of imatinib in a substantial proportion of patients with dcSSc. This is important in evaluating the relevance of this therapy in a chronic disease such as SSc.

Hyperglycemia-induced reactive oxygen species production can cause diabetes and its complications, including atherosclerosis. The role of mitochondrial DNA variants and mitochondrial copy number in the pathogenesis of diabetic atherogenesis is not well understood. We examined 36 diabetic patients who had undergone amputation for diabetic foot and seven non-diabetic patients who had undergone amputation after traumatic injury. Mitochondrial DNA was extracted and used for sequencing. Single nucleotide polymorphisms (SNPs) relative to the Cambridge reference sequence were analyzed. Mitochondrial DNA copy number was quantified by real-time PCR. Twenty-one novel variants were detected in 29 diabetic patients with arterial stenosis; six of the variants were heteroplasmic, and most occurred in highly evolutionarily conserved residues. These variants were more prevalent in patients with arterial stenosis than in those without stenosis. The novel variants included four in complex I (ND1: C3477A/C, A3523A/G; ND5: C13028A/C, C13060A/C), one in complex IV (COX1: T6090A/T), and one in rRNA (12srRNA: G857G/T). Compared with non-diabetic patients, the diabetic patients had significantly less mitochondrial DNA. Furthermore, among diabetic patients with arterial stenosis, there was a significant positive correlation between mitochondrial DNA copy number and the number of total SNPs. In conclusion, we identified six novel heteroplasmic mitochondrial DNA variants among diabetic patients with arterial stenosis, and we found that diabetic atherogenesis is associated with decreased amounts of mitochondrial DNA.

We consider estimation in logistic regression where some covariate variables may be missing at random. Satten and Kupper (1993, Journal of the American Statistical Association 88, 200-208) proposed estimating odds ratio parameters using methods based on the probability of exposure. By approximating a partial likelihood, we extend their idea and propose a method that estimates the cumulant-generating function of the missing covariate given observed covariates and surrogates in the controls. Our proposed method first estimates some lower order cumulants of the conditional distribution of the unobserved data and then solves a resulting estimating equation for the logistic regression parameter. A simple version of the proposed method is to replace a missing covariate by the summation of its conditional mean and conditional variance given observed data in the controls. We note that one important property of the proposed method is that, when the validation is only on controls, a class of inverse selection probability weighted semiparametric estimators cannot be applied because selection probabilities on cases are zeroes. The proposed estimator performs well unless the relative risk parameters are large, even though it is technically inconsistent. Small-sample simulations are conducted. We illustrate the method by an example of real data analysis.

Aliquots of ejaculated boar semen containing known numbers of spermatozoa were deposited into the caudal isthmus or rostral ampulla of the Fallopian tubes of gilts at, or immediately after, ovulation to assess regional influences on the rate of capacitation. Eggs were recovered during a second intervention 4, 5, 6 or 7 h after surgical insemination and were examined by phase-contrast microscopy. Results were obtained from ten animals in each of the 4-, 5- and 6-h groups and from eight animals in the 7-h group. With two exceptions, fertilized eggs were not recovered until 6 h after insemination into the isthmus, the proportion (45.6%) being significantly greater than the corresponding figure (1.4%) for ampullary insemination (P < 0.001). Similarly, the proportion of fertilized eggs recovered 7 h after insemination into the isthmus (58.7%) was significantly greater than after ampullary insemination (21.9%; P < 0.01). Numbers of spermatozoa associated with the zona pellucida remained low in all these instances, with mean figures per egg ranging from 0.3 to 3.8. Insemination into the isthmus gave a 1-2 h advantage in fertilization compared with insemination into the ampulla. Although relative rates of sperm cell progression to the site of fertilization may have contributed to this, there is strong evidence that rates of capacitation differ significantly in the respective portions of the Fallopian tube. Therefore, attention was focused on: (1) the viscous glycoprotein secretion in the caudal isthmus acting to remove seminal plasma from the sperm surface; and (2) the phase of sperm head binding to the isthmus epithelium. Gradients in local endocrine modulation by the adjacent ovary offer one explanation for the functional specialization of different regions of the Fallopian tubes.