What if artificial urinary sphincter is not possible? Feasibility and effectiveness of ProACT for patients with persistent stress urinary incontinence after radical prostatectomy treated by sling.

BACKGROUND: Stress urinary incontinence (SUI) is a major component of the post radical prostatectomy (RP) trifecta. Surgical treatments are sub-urethral slings, artificial urinary sphincter (AUS) and adjustable peri-urethral balloons (PUB) ProACT. All options are imperfect at best and persistent SUI is challenging when AUS is not manageable. AIMS: This study analyzed the cumulate experience of our 2 centers with offering PUB implantation for SUI post RP in patients with insufficient improvement from slings. MATERIALS & METHODS: This retrospective study reviewed all patients implanted with second line ProACT. The primary endpoint was continence, defined as 0 pads per day (PPD). The secondary endpoints were 50% decrease in PPD and increases in the Incontinence Quality of Life score (IQOL). Refilling and complications were reported. RESULTS: Between 2007 and 2016, 26 patients were implanted. Five patients have had adjuvant radiotherapy (18%). The mean follow-up was 36 months (±20; min 14-max 128). All patient presented with persistent SUI, using 2.3 PPD (±1; min 1-max 6), and only one sling was removed due to infection. After ProACT with an average 3 mL refilling (±1.2 min 2-max 6), 18 patients (66.7%) were continent. Eight of the remaining patients (29.6%) were improved; their number of PPD decreased from 2.6 to 1. The average IQOL score of those 8 patients increased by 20 points, from 53.4 up to 74.2 (P = .005). Overall 26 patients (96.3%) were improved. The remaining patient was not implanted because of an intraoperative urethral injury and is considered a failed case (3.7%). He had instead an AUS implantation. Three patients (14.8%) needed PUB replacement. CONCLUSION: The limited population of patients from both our centers who presented with persistent SUI after RP, despite sling placement, improved with PUB ProACT implantations without significant complications.

Paraphoma Crown Rot of Pyrethrum (Tanacetum cinerariifolium).

Pyrethrum (Tanacetum cinerariifolium) is commercially cultivated for the extraction of natural pyrethrin insecticides from the oil glands inside seed. Yield decline has caused significant yield losses in Tasmania during the last decade. A new pathogen of pyrethrum causing crown rot and reduced growth of the plants in yield decline affected fields of northern Tasmania was isolated from necrotic crown tissue and described as Paraphoma vinacea. Multigene phylogenetic identification of the pathogen also revealed that P. vinacea was a new species different from other Paraphoma type strains. Glasshouse pathogenicity experiments showed that P. vinacea significantly reduced belowground and total biomass of pyrethrum plants 2 months after inoculation. Dull-tan to reddish-brown discoloration of the cortical and subcortical crown tissue was observed in 100% of the infected plants. P. vinacea infected 75% of the plants inoculated with root dip and soil drench inoculation techniques in an inoculation optimization experiment. P. vinacea, the causal agent of Paraphoma crown rot disease, represents an important pathogen that will negatively impact the commercial cultivation of pyrethrum in Tasmania.

SNP marker discovery, linkage map construction and identification of QTLs for enhanced salinity tolerance in field pea (Pisum sativum L.).

BACKGROUND: Field pea (Pisum sativum L.) is a self-pollinating, diploid, cool-season food legume. Crop production is constrained by multiple biotic and abiotic stress factors, including salinity, that cause reduced growth and yield. Recent advances in genomics have permitted the development of low-cost high-throughput genotyping systems, allowing the construction of saturated genetic linkage maps for identification of quantitative trait loci (QTLs) associated with traits of interest. Genetic markers in close linkage with the relevant genomic regions may then be implemented in varietal improvement programs. RESULTS: In this study, single nucleotide polymorphism (SNP) markers associated with expressed sequence tags (ESTs) were developed and used to generate comprehensive linkage maps for field pea. From a set of 36,188 variant nucleotide positions detected through in silico analysis, 768 were selected for genotyping of a recombinant inbred line (RIL) population. A total of 705 SNPs (91.7%) successfully detected segregating polymorphisms. In addition to SNPs, genomic and EST-derived simple sequence repeats (SSRs) were assigned to the genetic map in order to obtain an evenly distributed genome-wide coverage. Sequences associated with the mapped molecular markers were used for comparative genomic analysis with other legume species. Higher levels of conserved synteny were observed with the genomes of Medicago truncatula Gaertn. and chickpea (Cicer arietinum L.) than with soybean (Glycine max [L.] Merr.), Lotus japonicus L. and pigeon pea (Cajanus cajan [L.] Millsp.). Parents and RIL progeny were screened at the seedling growth stage for responses to salinity stress, imposed by addition of NaCl in the watering solution at a concentration of 18 dS m-1. Salinity-induced symptoms showed normal distribution, and the severity of the symptoms increased over time. QTLs for salinity tolerance were identified on linkage groups Ps III and VII, with flanking SNP markers suitable for selection of resistant cultivars. Comparison of sequences underpinning these SNP markers to the M. truncatula genome defined genomic regions containing candidate genes associated with saline stress tolerance. CONCLUSION: The SNP assays and associated genetic linkage maps developed in this study permitted identification of salinity tolerance QTLs and candidate genes. This constitutes an important set of tools for marker-assisted selection (MAS) programs aimed at performance enhancement of field pea cultivars.

Synthesis of fluorinated catharanthine analogues and investigation of their biomimetic coupling with vindoline.

The syntheses of 20,20-difluorocatharanthine and congeners, starting from the naturally occurring catharanthine, are reported. The fluorinated catharanthine analogues were investigated as potential precursors to dimeric Vinca alkaloids of the vinflunine family. However, the biomimetic coupling of the fluorinated catharanthine derivatives with vindoline led to unexpected alkaloid structures, the formation of which was rationalized.

Semisynthesis of macrocarpal C and analogues by selective dehydration of macrocarpal A or B.

Macrocarpals A and C are structurally related compounds that have been extracted from different Eucalyptus species. Although macrocarpal C is of biological interest, its isolation in pure form is difficult to achieve. We report herein an efficient method for the semisynthesis of macrocarpal C by selective exo-dehydration of another member of the macrocarpal family, macrocarpal A. We also report the semisynthesis of three new macrocarpal structures derived from either macrocarpal A or B.

Cationic cyclization of 2-alkenyl-1,3-dithiolanes: diastereoselective synthesis of trans-decalins.

An unprecedented and highly diastereoselective 6-endo-trig cyclization of 2-alkenyl-1,3-dithiolanes has been developed yielding trans-decalins, an important scaffold present in numerous di- and triterpenes. The novelty of this 6-endo-trig cyclization stands in the stepwise mechanism involving 2-alkenyl-1,3-dithiolane, acting as a novel latent initiator. It is suggested that the thioketal opens temporarily under the influence of TMSOTf, triggering the cationic 6-endo-trig cyclization, and closes after C-C bond formation and diastereoselective protonation to terminate the process. DFT calculations confirm this mechanistic proposal and provide a rationale for the observed diastereoselectivity. The reaction tolerates a wide range of functionalities and nucleophilic partners within the substrate. We have also shown that the one-pot 6-endo-trig cyclization followed by in situ 1,3-dithiolane deprotection afford directly the corresponding ketone. This improvement allowed the achievement of the shortest total synthesis of triptophenolide and the shortest formal synthesis of triptolide.

Expedient synthesis of mequitazine an antihistaminic drug by palladium catalyzed allylic alkylation of sodium phenothiazinate.

A short and straightforward synthesis of the antihistaminic drug mequitazine is reported, based on an efficient palladium catalyzed allylic alkylation of 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate using sodium phenothiazinate in mild conditions.

Improving Rice Zinc Biofortification Success Rates Through Genetic and Crop Management Approaches in a Changing Environment.

Though rice is the predominant source of energy and micronutrients for more than half of the world population, it does not provide enough zinc (Zn) to match human nutritional requirements. Moreover, climate change, particularly rising atmospheric carbon dioxide concentration, reduces the grain Zn concentration. Therefore, rice biofortification has been recognized as a key target to increase the grain Zn concentration to address global Zn malnutrition. Major bottlenecks for Zn biofortification in rice are identified as low Zn uptake, transport and loading into the grain; however, environmental and genetic contributions to grain Zn accumulation in rice have not been fully explored. In this review, we critically analyze the key genetic, physiological and environmental factors that determine Zn uptake, transport and utilization in rice. We also explore the genetic diversity of rice germplasm to develop new genetic tools for Zn biofortification. Lastly, we discuss the strategic use of Zn fertilizer for developing biofortified rice.

The effect of post-harvest and packaging treatments on glucoraphanin concentration in broccoli (Brassica oleracea var. italica).

The effects of post-harvest and packaging treatments on glucoraphanin (4-methylsulfinylbutyl glucosinolate), the glucosinolate precursor of anticancer isothiocyanate sulforaphane [4-methylsulfinylbutyl isothiocyanate], were examined in broccoli (Brassica oleracea var. italica) during storage times. The results showed that at 20 degrees C, 55% loss of glucoraphanin concentration occurred in broccoli stored in open boxes during the first 3 days of the treatment and 56% loss was found in broccoli stored in plastic bags by day 7. Under both air and controlled atmosphere (CA) storage, glucoraphanin concentration appeared to fluctuate slightly during 25 days of storage and the concentrations under CA was significantly higher than those stored under air treatment. In modified atmosphere packaging (MAP) treatments, glucoraphanin concentration in air control packaging decreased significantly whereas there were no significant changes in glucoraphanin concentration in MAP with no holes at 4 degrees C and two microholes at 20 degrees C for up to 10 days. Decreases in glucoraphanin concentration occurred when the broccoli heads deteriorated. In the present study, the best method for preserving glucoraphanin concentration in broccoli heads after harvest was storage of broccoli in MAP and refrigeration at 4 degrees C. This condition maintained the glucoraphanin concentration for at least 10 days and also maintained the visual quality of the broccoli heads.

The effect of sulfur fertilizer on glucoraphanin levels in broccoli (B. oleracea L. var. italica) at different growth stages.

Three sulfur (S) treatements were imposed by applying gypsum to three broccoli cultivars (Claudia, Marathon, and TB-234) known to differ in glucoraphanin content of mature seeds. The S treatments were control (very low added S), low S (23 kg S ha(-)(1)), and high S (92 kg S ha(-)(1)). The gypsum applications during the early vegetative phase of the three broccoli cultivars increased S uptake and the glucoraphanin content in each plant organ. There were significant genotypic differences for the content of both S and glucoraphanin in all plant organs at different growth stages with gypsum applications. A large increase in S and glucoraphanin content was found in the green heads of broccoli and mature seeds. S present in glucoraphanin accounted for only 4-10% of total S content in broccoli heads. However, S present in glucoraphanin in mature seeds accounted for 40-46% of the total S in the seeds of moderate and high glucoraphanin cultivars (Marathon and TB-234). The partitioning of S into glucoraphanin also increased with gypsum applications. Differences in S uptake, S distribution between organs, and partitioning of S into glucoraphanin largely explained the differences in glucoraphanin content in the green heads and mature seeds for the three broccoli cultivars and three S treatments.

Bark and leaf chlorophyll fluorescence are linked to wood structural changes in Eucalyptus saligna.

Wood structure and wood anatomy are usually considered to be largely independent of the physiological processes that govern tree growth. This paper reports a statistical relationship between leaf and bark chlorophyll fluorescence and wood density. A relationship between leaf and bark chlorophyll fluorescence and the quantity of wood decay in a tree is also described. There was a statistically significant relationship between the leaf chlorophyll fluorescence parameter Fv/Fm and wood density and the quantity of wood decay in summer, but not in spring or autumn. Leaf chlorophyll fluorescence at 0.05 ms (the O step) could predict the quantity of wood decay in trees in spring. Bark chlorophyll fluorescence could predict wood density in spring using the Fv/Fm parameter, but not in summer or autumn. There was a consistent statistical relationship in spring, summer and autumn between the bark chlorophyll fluorescence parameter Fv/Fm and wood decay. This study indicates a relationship between chlorophyll fluorescence and wood structural changes, particularly with bark chlorenchyma.

Tolerance responses of Brassica juncea to salinity, alkalinity and alkaline salinity.

Soil salinity and alkalinity are common constraints to crop productivity in low rainfall regions of the world. These two stresses have been extensively studied but not the combined stress of alkaline salinity. To examine the effects of mild salinity (50mM NaCl) combined with alkalinity (5mM NaHCO3) on growth of Brassica juncea (L.) Czern., 30 genotypes were grown in hydroponics. Growth of all genotypes was substantially reduced by alkaline salinity after 4 weeks of stress. Based on large genotypic differences, NDR 8501 and Vaibhav were selected as tolerant and Xinyou 5 as highly sensitive for further detailed physiological study. Shoot and root biomass and leaf area of the selected genotypes showed greater reduction under alkaline salinity than salinity or alkalinity alone. Alkalinity alone imposed larger negative effect on growth than salinity. K+ and P concentrations in both shoot and root were significantly reduced by alkaline salinity but small difference existed among the selected genotypes. Leaf Fe concentration in Xinyou 5 decreased under alkaline salinity below a critical level of 50mgkg-1, which explained why more chlorosis and a larger growth reduction occurred than in NDR 8501 and Vaibhav. Relatively large shoot and root Na+ concentration also had additional adverse effect on growth under alkaline salinity. Low tissue K+, P and Fe concentrations by alkalinity were the major factors that reduced growth in the selected genotypes. Growth reduction by salinity was mainly caused by Na+ toxicity. Shoot Na+ concentration of NDR 8501 and Vaibhav was almost half those in Xinyou 5, suggesting NDR 8501 and Vaibhav excluded more Na+. However, Na+ exclusion was reduced by more than 50% under alkaline salinity than salinity in the selected genotypes. In conclusion, our results demonstrated that alkaline salinity reduced uptake of essential nutrients and Na+ exclusion that resulted in more negative consequences on growth than salinity alone.

Enantioselective synthesis of levomilnacipran.

A novel approach for the asymmetric synthesis of the active (1S,2R)-enantiomer of the antidepressant milnacipran is reported. The two stereogenic centers borne by the cyclopropane ring were sequentially installed starting from phenylacetic acid.

Asymmetric synthesis of (+)-mequitazine from quinine.

The first asymmetric synthesis of the antihistaminic drug mequitazine is reported. Our approach started from quinine, a Cinchona alkaloid, whose chiral information was exploited for setting up the stereogenic center of (+)-mequitazine.

On the elucidation of the mechanism of Vinca alkaloid fluorination in superacidic medium.

Detailed investigations on one of the key steps of the superacidic fluorination of Vinca alkaloids that is the origin of C20' activation are reported. While two different pathways can be envisioned for the emergence of the transient secondary carbocationic intermediate, isotopic labeling experiments unambiguously revealed the involvement of a 1,2-hydride shift mechanism.

Diastereoselective formal total synthesis of (+/-)-triptolide via a novel cationic cyclization of 2-alkenyl-1,3-dithiolane.

A concise and diastereoselective formal total synthesis of triptolide, a natural product with a wide range of biological properties, is described. The key reaction is an unprecedented 6-endo-Trig cationic cyclization of a 2-alkenyl-1,3-dithiolane precursor induced by TMSOTf as Lewis acid.

Physiological mechanisms of tolerance to high boron concentration in Brassica rapa.

Tolerance to high boron concentration in Brassica rapa was primarily due to low net boron uptake by the roots. However, in the two tolerant genotypes, 39-43% of boron uptake was retained in the tap roots, which limited boron accumulation in the leaves, and also contributed to boron tolerance. In the sensitive genotype, 99% of the increase in boron uptake caused by high soil boron accumulated in the leaves, particularly in the leaf margins. Despite higher transpiration rates, lower net boron uptake occurred in the tolerant genotypes. This result cannot be explained by passive boron uptake alone. Active boron efflux was probably responsible for differences in net boron uptake among tolerant and sensitive genotypes. Boron concentration was much lower in the cell walls than in the cell sap of leaves, indicating that storage of boron in the cell walls was not a tolerance mechanism. Despite high boron concentrations in the leaf symplasm, rates of photosynthesis, transpiration and growth were almost unaffected in the tolerant genotypes. The results demonstrate that boron tolerance in Brassica rapa involves boron exclusion at the root level, boron partitioning away from leaves and, as boron accumulates in leaves despite the first two mechanisms, boron tolerance of the leaf tissue itself.

Expedient total syntheses of rhein and diacerhein via Fries rearrangement.

Short and practical total syntheses of rhein (1) and diacerhein (2) have been achieved via a Fries rearrangement and bis-carbonylation strategy followed by cyclization in molten salt, starting from dibromoester 7.