Mechanistic and Kinetic Insights into OH-Initiated Atmospheric Oxidation of Hymexazol: A Computational Study.

Hymexazol is a volatile fungicide widely used in agriculture, causing its abundance in the atmosphere; thus, its atmospheric fate and conversion are of great importance when assessing its environmental impacts. Herein, we report a theoretical kinetic mechanism for the oxidation of hymexazol by OH radicals, as well as the subsequent reactions of its main products with O2 and then with NO by using the Rice-Ramsperger-Kassel-Marcus-based Master equation kinetic model on the potential energy surface explored at the ROCBS-QB3//M06-2X/aug-cc-pVTZ level. The predicted total rate constants ktotal(T, P) for the reaction between hymexazol and OH radicals show excellent agreement with scarcely available experimental values (e.g., 3.6 × 10-12 vs (4.4 ± 0.8) × 10-12 cm3/molecule/s at T = 300 K and P = 760 Torr); thus, the calculated kinetic parameters can be confidently used for modeling/simulation of N-heterocycle-related applications under atmospheric and even combustion conditions. The model shows that 3,4-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-5-yl (IM2), 3,5-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-4-yl (IM3), and (3-hydroxy-1,2-oxazol-5-yl)methyl (P8) are the main primary intermediates, which form the main secondary species of (3,4-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-5-yl)dioxidanyl (IM4), (3,5-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-4-yl)dioxidanyl (IM7), and ([(3-hydroxy-1,2-oxazol-5-yl)methyl]dioxidanyl (IM11), respectively, through the reactions with O2. The main secondary species then can react with NO to form the main tertiary species, namely, (3,4-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-5-yl)oxidanyl (P19), (3,5-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-4-yl)oxidanyl (P21), and [(3-hydroxy-1,2-oxazol-5-yl)methyl]oxidanyl (P23), respectively, together with NO2. Besides, hymexazol could be a persistent organic pollutant in the troposphere due to its calculated half-life τ1/2 of 13.7-68.1 h, depending on the altitude.

Robot Assistants for Perimetry: A Study of Patient Experience and Performance.

PURPOSE: People enjoy supervision during visual field assessment, although resource demands often make this difficult. We evaluated outcomes and subjective experience of methods of receiving feedback during perimetry, with specific goals to compare a humanoid robot to a computerized voice in participants with minimal prior perimetric experience. Human feedback and no feedback also were compared. METHODS: Twenty-two younger (aged 21-31 years) and 18 older (aged 52-76 years) adults participated. Visual field tests were conducted using an Octopus 900, controlled with the Open Perimetry Interface. Participants underwent four tests with the following feedback conditions: (1) human, (2) humanoid robot, (3) computer speaker, and (4) no feedback, in random order. Feedback rules for the speaker and robot were identical, with the difference being a social interaction with the robot before the test. Quantitative perimetric performance compared mean sensitivity (dB), fixation losses, and false-positives. Subjective experience was collected via survey. RESULTS: There was no significant effect of feedback type on the quantitative measures. For younger adults, the human and robot were preferred to the computer speaker (P < 0.01). For older adults, the experience rating was similar for the speaker and robot. No feedback was the least preferred option of 77% younger and 50% older adults. CONCLUSIONS: During perimetry, a social robot was preferred to a computer speaker providing the same feedback, despite the robot not being visible during the test. Making visual field testing more enjoyable for patients and operators may improve compliance and attitude to perimetry, leading to improved clinical outcomes. TRANSLATIONAL RELEVANCE: Our data suggest that humanoid robots can replace some aspects of human interaction during perimetry and are preferable to receiving no human feedback.

Metastatic Melanoma of the Optic Nerve Sheath.

A 23-year-old man with a history of metastatic melanoma developed painful vision loss to counting fingers with enhancement of optic nerve on contrast-enhanced magnetic resonance imaging (MRI) and received a diagnosis of optic neuritis from an outside hospital. Despite empiric corticosteroid therapy, the patient worsened and developed secondary central retinal vein occlusion with further deterioration of vision. Repeat MRI demonstrated optic nerve sheath (ONS) involvement suggestive of optic perineuritis (OPN) and an ONS biopsy confirmed a rare case of isolated metastatic melanoma. Our case highlights the clinical and radiographic features that can mimic OPN and delay diagnosis and treatment.

Rapid divergence and convergence of life-history in experimentally evolved Drosophila melanogaster.

Laboratory selection experiments are alluring in their simplicity, power, and ability to inform us about how evolution works. A longstanding challenge facing evolution experiments with metazoans is that significant generational turnover takes a long time. In this work, we present data from a unique system of experimentally evolved laboratory populations of Drosophila melanogaster that have experienced three distinct life-history selection regimes. The goal of our study was to determine how quickly populations of a certain selection regime diverge phenotypically from their ancestors, and how quickly they converge with independently derived populations that share a selection regime. Our results indicate that phenotypic divergence from an ancestral population occurs rapidly, within dozens of generations, regardless of that population's evolutionary history. Similarly, populations sharing a selection treatment converge on common phenotypes in this same time frame, regardless of selection pressures those populations may have experienced in the past. These patterns of convergence and divergence emerged much faster than expected, suggesting that intermediate evolutionary history has transient effects in this system. The results we draw from this system are applicable to other experimental evolution projects, and suggest that many relevant questions can be sufficiently tested on shorter timescales than previously thought.

Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology.

Elderly persons are more susceptible to RSV-induced pneumonia than young people, but the molecular mechanism underlying this susceptibility is not well understood. In this study, we used an aged mouse model of RSV-induced pneumonia to examine how aging alters the lung pathology, modulates antiviral gene expressions, and the production of inflammatory cytokines in response to RSV infection. Young (2-3 months) and aged (19-21 months) mice were intranasally infected with mucogenic or non-mucogenic RSV strains, lung histology was examined, and gene expression was analyzed. Upon infection with mucogenic strains of RSV, leukocyte infiltration in the airways was elevated and prolonged in aged mice compared to young mice. Minitab factorial analysis identified several antiviral genes that are influenced by age, infection, and a combination of both factors. The expression of five antiviral genes, including pro-inflammatory cytokines IL-1ß and osteopontin (OPN), was altered by both age and infection, while age was associated with the expression of 15 antiviral genes. Both kinetics and magnitude of antiviral gene expression were diminished as a result of older age. In addition to delays in cytokine signaling and pattern recognition receptor induction, we found TLR7/8 signaling to be impaired in alveolar macrophages in aged mice. In vivo, induction of IL-1ß and OPN were delayed but prolonged in aged mice upon RSV infection compared to young. In conclusion, this study demonstrates inherent differences in response to RSV infection in young vs. aged mice, accompanied by delayed antiviral gene induction and cytokine signaling.

The temporal evolution and global spread of Cauliflower mosaic virus, a plant pararetrovirus.

Cauliflower mosaic virus (CaMV) is a plant pararetrovirus with a double-stranded DNA genome. It is the type member of the genus Caulimovirus in the family Caulimoviridae. CaMV is transmitted by sap inoculation and in nature by aphids in a semi-persistent manner. To investigate the patterns and timescale of CaMV migration and evolution, we sequenced and analyzed the genomes of 67 isolates of CaMV collected mostly in Greece, Iran, Turkey, and Japan together with nine published sequences. We identified the open-reading frames (ORFs) in the genomes and inferred their phylogeny. After removing recombinant sequences, we estimated the substitution rates, divergence times, and phylogeographic patterns of the virus populations. We found that recombination has been a common feature of CaMV evolution, and that ORFs I-V have a different evolutionary history from ORF VI. The ORFs have evolved at rates between 1.71 and 5.81×10(-4) substitutions/site/year, similar to those of viruses with RNA or ssDNA genomes. We found four geographically confined lineages. CaMV probably spread from a single population to other parts of the world around 400-500 years ago, and is now widely distributed among Eurasian countries. Our results revealed evidence of frequent gene flow between populations in Turkey and those of its neighboring countries, with similar patterns observed for Japan and the USA. Our study represents the first report on the spatial and temporal spread of a plant pararetrovirus.

Focal cryotherapy in the treatment of localized prostate cancer.

BACKGROUND: The management choice for newly diagnosed localized prostate cancer presents a challenge to both the physician and the patient. Traditionally, surgery and radiation therapy have been the most commonly recommended options. More recently, active surveillance is recommended as the preferred management choice for a subset of men with localized, low-risk cancer. Recent reports also suggest that focal cryotherapy may be considered as a management option for selected cases of clinically localized prostate cancer. METHODS: A review of the literature on focal cryotherapy from 2002 to 2012 was performed. Outcomes on cancer control, complications, and quality of life were extracted and assessed. RESULTS: The biochemical disease-free survival at 5 years is comparable to whole gland treatment modalities. Complications are minimal and comparable with other local treatment modalities. CONCLUSIONS: Focal cryotherapy is safe and effective, and it may improve failure rates in men who initially pursue active surveillance protocols. Early outcomes with cancer control are encouraging.

Turnip mosaic potyvirus probably first spread to Eurasian brassica crops from wild orchids about 1000 years ago.

Turnip mosaic potyvirus (TuMV) is probably the most widespread and damaging virus that infects cultivated brassicas worldwide. Previous work has indicated that the virus originated in western Eurasia, with all of its closest relatives being viruses of monocotyledonous plants. Here we report that we have identified a sister lineage of TuMV-like potyviruses (TuMV-OM) from European orchids. The isolates of TuMV-OM form a monophyletic sister lineage to the brassica-infecting TuMVs (TuMV-BIs), and are nested within a clade of monocotyledon-infecting viruses. Extensive host-range tests showed that all of the TuMV-OMs are biologically similar to, but distinct from, TuMV-BIs and do not readily infect brassicas. We conclude that it is more likely that TuMV evolved from a TuMV-OM-like ancestor than the reverse. We did Bayesian coalescent analyses using a combination of novel and published sequence data from four TuMV genes [helper component-proteinase protein (HC-Pro), protein 3(P3), nuclear inclusion b protein (NIb), and coat protein (CP)]. Three genes (HC-Pro, P3, and NIb), but not the CP gene, gave results indicating that the TuMV-BI viruses diverged from TuMV-OMs around 1000 years ago. Only 150 years later, the four lineages of the present global population of TuMV-BIs diverged from one another. These dates are congruent with historical records of the spread of agriculture in Western Europe. From about 1200 years ago, there was a warming of the climate, and agriculture and the human population of the region greatly increased. Farming replaced woodlands, fostering viruses and aphid vectors that could invade the crops, which included several brassica cultivars and weeds. Later, starting 500 years ago, inter-continental maritime trade probably spread the TuMV-BIs to the remainder of the world.

The frequency of osteoporosis screening in men with inflammatory bowel disease.

Osteoporosis is underdiagnosed in men, and osteoporosis-related fractures carry high morbidity and mortality. Recent recommendations on osteoporosis screening in men from the American College of Physicians state that screening and risk factor assessment need to occur earlier in men at high risk. Men with inflammatory bowel disease are at high risk for osteoporosis and fragility fractures due to corticosteroid use, malabsorption from intestinal resection, potential vitamin D deficiency, and fluctuations in weight. This study examines the rate of corticosteroid use, vitamin D screening, and bone mineral density screening of men with inflammatory bowel disease in a gastroenterology practice. The vast majority of men with inflammatory bowel disease are at high risk for osteoporosis. Screening and risk factor assessment should be emphasized.

Bis[1-(p-chlorophenyl)-5-isopropylbiguanide-kappa2N2,N4]nickel(II) dichloride dimethylformamide solvate.

The asymmetric unit of the title compound, [Ni(C(11)H(16)ClN(5))(2)]Cl(2).C(3)H(7)NO, contains one monomeric nickel(II) complex cation, two Cl(-) anions and one dimethylformamide solvent molecule. The Ni atom is coordinated to each of two 1-(p-chlorophenyl)-5-isopropylbiguanide (proguanil) ligands via two N atoms. The complex exhibits a square-planar coordination, with the Ni atom lying 0.021 (2) A out of the basal plane. The crystal packing is characterized by several hydrogen bonds.

[Synthesis and crystalline structure of cis-monochloro(dimenthylsulfoxide)]. / Synthèse et structure cristalline du cis-monochloro(diméthylsulfoxyde) (metforminuro)platine (II).

The synthesis of cis-monochloro(dimethylsulfoxide)(metforminuro) platine(II) was investigated. It crystallizes in the monoclinic system, space group P 2(1)/c with Z=4. The cell parameters are: a=9.173(2); b=11.286( 2); c=12.556( 3) (A); b=99.69(2) degrees. The structure of this compound was refined to R=0.031 and wR=0.038 using 1461 independent reflexions with I>3 s(I). The platinum coordination is square planar, built up from one Cl, one O from the dimethylsulfoxide, and one bidentate chelating ligand (metforminure anion) via the two imine nitrogen atoms in cis position. The negative charge of the metforminure ligand ensures the electric neutrality in the complex. The crystal packing is characterized by four hydrogen bonds, one of which is bifurcated (involving Cl atom (intramolecular bonding) and O(i) (intermolecular bonding; symmetry code i: x, 3/2-y; 1/2+z).

[Crystallochemistry of copper (II) and zinc (II) chelates by nonsteroidal antiinflammatory drugs]. / Cristallochimie des complexes à visée thérapeutique du cuivre (II) et du zinc (II) par des anti-inflammatoires non-stéroïdiens.

Copper(II) and zinc(II) chelates by some non-steroidal antiinflammatory drugs NSAIDs (niflumic acid, indomethacin) and 3,5-diisopropylsalicylic acid (DIPS) were characterized by single X-ray diffraction methods. Copper(II) complexes by these two types of chelates are binuclear compounds, with Cu(2)(DIPS)(4)L(2) or Cu(2)(AINS)(4)L(2) formula (L=axial non-NSAID ligand such as diethylether, dimethylsulfoxide DMSO). In zinc(II) complex by DIPS, the metal ion is tetrahedrally coordinated and the corresponding compound is mononuclear with Zn(DIPS)(2)(DMSO)(2) formula. These copper(II) and zinc(II) complexes were found to be more active than their parent drugs from the antiinflammatory and anticonvulsant properties. It was pointed out that the Cu(2)(DIPS)(4)L(2) complexes (L=diethylether, N,N-dimethylformamide) exhibited no rotorod toxicity when examined for anticonvulsant activity using the seizure produced by maximal electroshock, following oral administration to rats.

In vivo inhibition of nitric oxide synthase by bisisothiouronium and bisguanidinium salts.

The ability of two S,S'-(alkane-1,omega-diyl) bisisothiouronium dibromides, three N,N'-(alkane-1, omega-diyl) bis guanidinium dinitrates and N,N'-bis (3-guanidinopropyl)piperazine dinitrate to inhibit constitutive (i.e. endothelial and neuronal forms) and inducible forms of nitric oxide synthases has been evaluated in vivo. These compounds, synthesized by two of us (J. C. L. and C. S.), have been tested in vivo; they were administered simultaneously with an irritant (carrageenan lambda) into the pleural cavity. The amount of nitrites collected 0.5 and 7 hours after this injection can be considered as an indicator of nitric oxide (NO) production. According to previous data, the first harvesting time can be related to activation of constitutive NO synthases and the second to activation of inducible NO synthases. These substances significantly inhibited nitrite production as did 2-methyl-2-thiopseudourea sulphate, previously described as a potent inhibitor of NO synthases and considered as the reference compound. The inhibiting effect varied according to the chemical structure of the compounds. Results were significantly different from controls at 0.5 h only with the S,S'-(octane-1,8-diyl) bisisothiouronium dibromide and the S,S'-(nonane-1,9-diyl) bisisothiouronium dibromide at the highest concentration, N,N'-(heptane-1,7-diyl) bisguanidinium dinitrate and N,N'-bis (3-guanidinopropyl)piperazine dinitrate. At 7 h, all the results were significantly different from controls, with a major effect observed with N,N'-(heptane-1,7-diyl) bisguanidinium dinitrate. The most active substances exerted similar effects to the reference substance.