& AbstractObjective: To evaluate the effectiveness and tolerability of tapentadol PR monotherapy versus tapentadol PR/pregabalin combination therapy for severe, chronic low back pain with a neuropathic component. Methods: Eligible patients had painDETECT "unclear" or "positive" ratings and average pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) at baseline. Patients were titrated to tapentadol PR 300 mg/day over 3 weeks. Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadol PR (500 mg/day) or tapentadol PR (300 mg/day)/pregabalin (300 mg/day) during an 8-week comparative period. Results: In the per-protocol population (n = 288), the effectiveness of tapentadol PR was clinically and statistically comparable to tapentadol PR/pregabalin based on the change in pain intensity from randomization to final evaluation (LOCF; LSMD [95% CI], À0.066 [À0.57, 0.43]; P < 0.0001 for noninferiority). Neuropathic pain and quality-of-life measures improved significantly in both groups. Tolerability was good in both groups, in line with prior trials in the high
The genetic structure of Mycosphaerella fijiensis populations around the world was examined using DNA restriction fragment length polymorphism (RFLP) markers. Allele frequencies at 19 nuclear RFLP loci were estimated in a sample of 136 M. fijiensis isolates from five geographical populations representative of banana‐producing areas (South‐East Asia including the Philippines and Papua New Guinea, Africa, Latin America and Pacific Islands). Within each population, gametic disequilibrium tests between the 19 nuclear RFLP loci were mainly non significant (P > 0.05), indicating that random sexual reproduction occurred in these populations. All M. fijiensis populations had a high level of genotypic and allelic diversity (H, gene diversity: 0.25–0.59). The highest levels of gene diversity were found in the two South‐East Asian populations (H: 0.57 and 0.59). Most of the alleles (> 88%) detected in Africa, Latin America and Pacific Islands populations were also detected in South‐East Asian populations. Furthermore, a high and significant (P < 0.05) level of genetic differentiation was observed among M. fijiensis geographical populations (overall estimate of Fst: 0.32). These results were consistent with the hypothesis that M. fijiensis originated in South‐East Asia and spread recently to other parts of the world. The level of allelic diversity in M. fijiensis populations from regions other than South‐East Asia was drastically reduced, indicating founder effects. The data also suggested rare occurrence of migration of M. fijiensis between continents.
Citrus are natural hosts of five viroid species: Citrus exocortis viroid (CEVd), Citrus bent leaf viroid (CBLVd), Hop stunt viroid (HSVd), Citrus viroid III (CVd-III), and Citrus viroid IV (CVd-IV). CEVd and specific sequence variants of HSVd are the causal agents of the wellknown diseases of citrus, exocortis and cachexia. Other viroids have been found to induce different degrees of stunting. Since commercial citrus trees are commonly infected with mixtures of these viroids, only limited information is available on their effect in species other than Etrog citron. A field assay was conducted to establish the effect of each viroid on Commune clementine trees grafted on Pomeroy trifoliate orange. Infected trees were periodically monitored over a 12-year period (1990 to 2002) for symptom expression, growth, and fruit yield. Only CEVd caused bark scaling on the trifoliate orange rootstock and marked dwarfing, both characteristic of exocortis disease as initially described. In addition, very conspicuous bumps were observed in the wood of the rootstock after removing the bark. Only those HSVd variants, previously characterized as pathogenic in several cachexia-sensitive species, induced pits and gum deposits characteristic of this disease in the clementine scion. Bark cracking symptoms on the trifoliate orange rootstock were also observed. They were associated with CVd-IV, HSVd, or CEVd infection, but in the latter, they were only clearly observed in trees that showed mild scaling. Other abnormalities (deep pits, crests, and gummy pits) were not associated with viroid infection. No specific symptoms resulted from infection with CBLVd and CVd-III. HSVd, CVd-IV, and CBLVd had little or no effect in growth and yield, whereas CEVd and CVd-III caused a significant reduction of growth and yield, which became more pronounced over time with CEVd infection. Yield reduction was associated mainly with loss of production of large fruits. In general, there was a good correlation between reduction in vegetative growth and yield.
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