An effector from the Huanglongbing-associated pathogen targets citrus proteases

The citrus industry is facing an unprecedented challenge from Huanglongbing (HLB). All cultivars can be affected by the HLB-associated bacterium ‘Candidatus Liberibacter asiaticus’ (CLas) and there is no known resistance. Insight into HLB pathogenesis is urgently needed in order to develop effective management strategies. Here, we use Sec-delivered effector 1 (SDE1), which is conserved in all CLas isolates, as a molecular probe to understand CLas virulence. We show that SDE1 directly interacts with citrus papain-like cysteine proteases (PLCPs) and inhibits protease activity. PLCPs are defense-inducible and exhibit increased protein accumulation in CLas-infected trees, suggesting a role in citrus defense responses. We analyzed PLCP activity in field samples, revealing specific members that increase in abundance but remain unchanged in activity during infection. SDE1-expressing transgenic citrus also exhibit reduced PLCP activity. These data demonstrate that SDE1 inhibits citrus PLCPs, which are immune-related proteases that enhance defense responses in plants

Protocol for Fit Bodies, Fine Minds: a randomized controlled trial on the affect of exercise and cognitive training on cognitive functioning in older adults

Background. Declines in cognitive functioning are a normal part of aging that can affect daily functioning and quality of life. This study will examine the impact of an exercise training program, and a combined exercise and cognitive training program, on the cognitive and physical functioning of older adults. Methods/Design. Fit Bodies, Fine Minds is a randomized, controlled trial. Community-dwelling adults, aged between 65 and 75 years, are randomly allocated to one of three groups for 16 weeks. The exercise-only group do three 60-minute exercise sessions per week. The exercise and cognitive training group do two 60-minute exercise sessions and one 60-minute cognitive training session per week. A no-training control group is contacted every 4 weeks. Measures of cognitive functioning, physical fitness and psychological well-being are taken at baseline (0 weeks), post-test (16 weeks) and 6-month follop (40 weeks). Qualitative responses to the program are taken at post-test. Discussion. With an increasingly aged population, interventions to improve the functioning and quality of life of older adults are particularly important. Exercise training, either alone or in combination with cognitive training, may be an effective means of optimizing cognitive functioning in older adults. This study will add to the growing evidence base on the effectiveness of these interventions. Trial Registration. Australian Clinical Trials Register: ACTRN012607000151437

High and immeasurable ankle-brachial index as predictor of poor amputation-free survival in critical limb ischemia

OBJECTIVE: The objective of this study was to assess the prognostic value of a high or immeasurable ankle-brachial index (ABI) at baseline for major amputation and amputation-free survival (AFS) in patients with critical limb ischemia (CLI). METHODS: Data from two recent trials in patients with CLI and proven infrapopliteal arterial obstructive disease were pooled. Patients were allocated to the low (1.4)/immeasurable ABI subgroup. Major amputation and AFS rates were compared. Hazard ratios for major amputation and death were calculated. The net reclassification improvement of incorporating high/immeasurable ABI in the Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III) prediction model was derived. RESULTS: There were 146 patients (56.2%) who had a low ABI, 81 patients (31.2%) who had an intermediate ABI, and 33 patients (12.7%) who had a high/immeasurable ABI at baseline. Patients with high/immeasurable ABI showed higher 5-year major amputation (52.1%) and lower 5-year AFS (5.0%) rates than the intermediate (25.5% and 41.6%, respectively) and low ABI patients (23.5% and 46.9%, respectively; both P < .001). This same trend was observed in subgroup analysis of diabetics and nondiabetics. Adjusted hazard ratio of high/immeasurable ABI for major amputation/death risk was 2.93 (P < .001). Adding a high/immeasurable ABI as model factor to the PREVENT III model yielded a net reclassification index of 0.38 (P < .0001). CONCLUSIONS: A high/immeasurable ABI in patients with CLI and infrapopliteal arterial obstructive disease is an independent risk factor of major amputation and of poor AFS, in both diabetics and nondiabetics. Incorporating high/immeasurable ABI in the PREVENT III prediction model improves its performance

Long-Term Follow-up of the PADI Trial : Percutaneous Transluminal Angioplasty Versus Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia

BACKGROUND: Clinical outcomes reported after treatment of infrapopliteal lesions with drug-eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent (PTA-BMS) through midterm follow-up in patients with critical limb ischemia. In the present study, long-term results of treatment of infrapopliteal lesions with DESs are presented. METHODS AND RESULTS: Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA-BMS or DESs with paclitaxel. Long-term follow-up consisted of annual assessments up to 5 years after treatment or until a clinical end point was reached. Clinical end points were major amputation (above ankle level), infrapopliteal surgical or endovascular reintervention, and death. Preserved primary patency (≤50% restenosis) of treated lesions was an additional morphological end point, assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with DESs and 66 limbs (64 patients) were treated with PTA-BMS. The estimated 5-year major amputation rate was lower in the DES arm (19.3% versus 34.0% for PTA-BMS; P=0.091). The 5-year rates of amputation- and event-free survival (survival free from major amputation or reintervention) were significantly higher in the DES arm compared with PTA-BMS (31.8% versus 20.4%, P=0.043; and 26.2% versus 15.3%, P=0.041, respectively). Survival rates were comparable. The limited available morphological results showed higher preserved patency rates after DESs than after PTA-BMS at 1, 3, and 4 years of follow-up. CONCLUSIONS: Both clinical and morphological long-term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with DES compared with PTA-BMS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289

Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial

BACKGROUND: Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. METHODS AND RESULTS: Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia-related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). CONCLUSIONS: In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289

Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial

BACKGROUND: Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. METHODS AND RESULTS: Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia-related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). CONCLUSIONS: In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289