An Experimentalists Guide to Electrosynthesis: The Shono Oxidation

Electrosynthesis is a powerful method to functionalise organic molecules without the need to use chemical reagents or protecting groups, yet it is not widely used in synthesis. In this study, we investigated the Shono oxidation of a tertiary amide (electrochemical functionalisation of a C–H bond adjacent to an amide nitrogen atom), demonstrating the value of performing cyclic voltammetry, varying voltage and charge per mole, selection of electrolyte and electrode material. We demystify the process to demonstrate a simple relationship between oxidation potential, and charge transfer required, which affords a high conversion to the desired alpha-methoxylated product using an undivided experimental cell

American Academy of Optometry Microbial Keratitis Think Tank

SIGNIFICANCE Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain

Measuring benefits and patients' satisfaction when glasses are not needed after cataract and presbyopia surgery: scoring and psychometric validation of the Freedom from Glasses Value Scale (FGVS©)

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to reduce the number of items, create a scoring method and assess the psychometric properties of the Freedom from Glasses Value Scale (FGVS), which measures benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal intraocular lens (IOL) surgery.</p> <p>Methods</p> <p>The 21-item FGVS, developed simultaneously in French and Spanish, was administered by phone during an observational study to 152 French and 152 Spanish patients who had undergone cataract or presbyopia surgery at least 1 year before the study. Reduction of items and creation of the scoring method employed statistical methods (principal component analysis, multitrait analysis) and content analysis. Psychometric properties (validation of the structure, internal consistency reliability, and known-group validity) of the resulting version were assessed in the pooled population and per country.</p> <p>Results</p> <p>One item was deleted and 3 were kept but not aggregated in a dimension. The other 17 items were grouped into 2 dimensions ('global evaluation', 9 items; 'advantages', 8 items) and divided into 5 sub-dimensions, with higher scores indicating higher benefit of surgery. The structure was validated (good item convergent and discriminant validity). Internal consistency reliability was good for all dimensions and sub-dimensions (Cronbach's alphas above 0.70). The FGVS was able to discriminate between patients wearing glasses or not after surgery (higher scores for patients not wearing glasses). FGVS scores were significantly higher in Spain than France; however, the measure had similar psychometric performances in both countries.</p> <p>Conclusions</p> <p>The FGVS is a valid and reliable instrument measuring benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal IOL surgery.</p

The aging Canadian population and hospitalizations for acute myocardial infarction: projection to 2020

<p>Abstract</p> <p>Background</p> <p>The risk of experiencing an acute myocardial infarction (AMI) increases with age and Canada's population is aging. The objective of this analysis was to examine trends in the AMI hospitalization rate in Canada between 2002 and 2009 and to estimate the potential increase in the number of AMI hospitalizations over the next decade.</p> <p>Methods</p> <p>Aggregated data on annual AMI hospitalizations were obtained from the Canadian Institute for Health Information for all provinces and territories, except Quebec, for 2002/03 and 2009/10. Using these data in a Poisson regression model to control for age, gender and year, the rate of AMI hospitalizations was extrapolated between 2010 and 2020. The extrapolated rate and Statistics Canada population projections were used to estimate the number of AMI hospitalizations in 2020.</p> <p>Results</p> <p>The rates of AMI hospitalizations by gender and age group showed a decrease between 2002 and 2009 in patients aged ≥ 65 years and relatively stable rates in those aged < 64 years in both males and females. However, the total number of AMI hospitalizations in Canada (excluding Quebec) is projected to increase by 4667 from 51847 in 2009 to 56514 in 2020, a 9.0% increase. Inflating this number to account for the unavailable Quebec data results in an increase of approximately 6200 for the whole of Canada. This would amount to an additional cost of between $46 and$54 million and sensitivity analyses indicate that it could be between $36 and$65 million.</p> <p>Conclusions</p> <p>Despite projected decreasing or stable rates of AMI hospitalization, the number of hospitalizations is expected to increase substantially as a result of the aging of the Canadian population. The cost of these hospitalizations will be substantial. An increase of this extent in the number of AMI hospitalizations and the ensuing costs would significantly impact the already over-stretched Canadian healthcare system.</p

A Multilevel Analysis of the Impact of Socio-Structural and Environmental Influences on Condom Use Among Female Sex Workers

This study uses multilevel analysis to examine individual, organizational and community levels of influence on condom use among female commercial sex workers (FSW) in the Philippines. A randomized controlled study involving 1,382 female commercial sex workers assigned to three intervention groups consisting of peer education, managerial training, combined peer and managerial intervention and a usual care control group was conducted. The results of the multilevel analysis show that FSWs who work in establishments with condom use rules tend to have a higher level of condom use (β = .70, P < 0.01). Among the different intervention groups, the combined peer and managerial intervention had the largest effect on condom use (β = 1.30, P < 0.01) compared with the usual care group. Using a three-level hierarchical model, we found that 62% of the variation lies within individuals, whereas 24% and 14% of the variation lies between establishments, and communities, respectively. Standard errors were underestimated when clustering of the FSWs in the different establishments and communities were not taken into consideration. The results demonstrate the importance of using multilevel analysis for community-based HIV/AIDS intervention programs to examine individual, establishment and community effects

Recovery from depressive symptoms, state anxiety and post-traumatic stress disorder in women exposed to physical and psychological, but not to psychological intimate partner violence alone: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>It is well established that intimate male partner violence (IPV) has a high impact on women's mental health. It is necessary to further investigate this impact longitudinally to assess the factors that contribute to its recovery or deterioration. The objective of this study was to assess the course of depressive, anxiety and post-traumatic stress disorder (PTSD) symptoms and suicidal behavior over a three-year follow-up in female victims of IPV.</p> <p>Methods</p> <p>Women (n = 91) who participated in our previous cross-sectional study, and who had been either physically/psychologically (n = 33) or psychologically abused (n = 23) by their male partners, were evaluated three years later. A nonabused control group of women (n = 35) was included for comparison. Information about mental health status and lifestyle variables was obtained through face-to-face structured interviews.</p> <p>Results</p> <p>Results of the follow-up study indicated that while women exposed to physical/psychological IPV recovered their mental health status with a significant decrease in depressive, anxiety and PTSD symptoms, no recovery occurred in women exposed to psychological IPV alone. The evolution of IPV was also different: while it continued across both time points in 65.21% of psychologically abused women, it continued in only 12.12% of physically/psychologically abused women while it was reduced to psychological IPV in 51.5%. Hierarchical multiple regression analyses indicated that cessation of physical IPV and perceived social support contributed to mental health recovery, while a high perception of lifetime events predicted the continuation of PTSD symptoms.</p> <p>Conclusion</p> <p>This study shows that the pattern of mental health recovery depends on the type of IPV that the women had been exposed to. While those experiencing physical/psychological IPV have a higher likelihood of undergoing a cessation or reduction of IPV over time and, therefore, could recover, women exposed to psychological IPV alone have a high probability of continued exposure to the same type of IPV with a low possibility of recovery. Thus, women exposed to psychological IPV alone need more help to escape from IPV and to recuperate their mental health. Longitudinal studies are needed to improve knowledge of factors promoting or impeding health recovery to guide the formulation of policy at individual, social and criminal justice levels.</p

A nocturnal atmospheric loss of CH2I2 in the remote marine boundary layer.

Ocean emissions of inorganic and organic iodine compounds drive the biogeochemical cycle of iodine and produce reactive ozone-destroying iodine radicals that influence the oxidizing capacity of the atmosphere. Di-iodomethane (CH2I2) and chloro-iodomethane (CH2ICl) are the two most important organic iodine precursors in the marine boundary layer. Ship-borne measurements made during the TORERO (Tropical Ocean tRoposphere Exchange of Reactive halogens and Oxygenated VOC) field campaign in the east tropical Pacific Ocean in January/February 2012 revealed strong diurnal cycles of CH2I2 and CH2ICl in air and of CH2I2 in seawater. Both compounds are known to undergo rapid photolysis during the day, but models assume no night-time atmospheric losses. Surprisingly, the diurnal cycle of CH2I2 was lower in amplitude than that of CH2ICl, despite its faster photolysis rate. We speculate that night-time loss of CH2I2 occurs due to reaction with NO3 radicals. Indirect results from a laboratory study under ambient atmospheric boundary layer conditions indicate a k CH2I2+NO3 of ≤4 × 10-13 cm3 molecule-1 s-1; a previous kinetic study carried out at ≤100 Torr found k CH2I2+NO3 of 4 × 10-13 cm3 molecule-1 s-1. Using the 1-dimensional atmospheric THAMO model driven by sea-air fluxes calculated from the seawater and air measurements (averaging 1.8 +/- 0.8 nmol m-2 d-1 for CH2I2 and 3.7 +/- 0.8 nmol m-2 d-1 for CH2ICl), we show that the model overestimates night-time CH2I2 by >60 % but reaches good agreement with the measurements when the CH2I2 + NO3 reaction is included at 2-4 × 10-13 cm3 molecule-1 s-1. We conclude that the reaction has a significant effect on CH2I2 and helps reconcile observed and modeled concentrations. We recommend further direct measurements of this reaction under atmospheric conditions, including of product branching ratios.LJC acknowledges NERC (NE/J00619X/1) and the National Centre for Atmospheric Science (NCAS) for funding. The laboratory work was supported by the NERC React-SCI (NE/K005448/1) and RONOCO (NE/F005466/1) grants.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s10874-015-9320-

MMP-13 stimulates osteoclast differentiation and activation in tumour breast bone metastases

INTRODUCTION: The increased bone degradation in osteolytic metastases depends on stimulation of mature osteoclasts and on continuous differentiation of new pre-osteoclasts. Metalloproteinases (MMP)-13 is expressed in a broad range of primary malignant tumours and it is emerging as a novel biomarker. Recent data suggest a direct role of MMP-13 in dissolving bone matrix complementing the activity of MMP-9 and other enzymes. Tumour-microenvironment interactions alter gene expression in malignant breast tumour cells promoting osteolytic bone metastasis. Gene expression profiles revealed that MMP-13 was among the up-regulated genes in tumour-bone interface and its abrogation reduced bone erosion. The precise mechanism remained not fully understood. Our purpose was to further investigate the mechanistic role of MMP-13 in bone osteolytic lesions. METHODS: MDA-MB-231 breast cancer cells that express MMP-13 were used as a model for in vitro and in vivo experiments. Conditioned media from MDA-MB-231 cells were added to peripheral blood mononuclear cultures to monitor pre-osteoclast differentiation and activation. Bone erosion was evaluated after injection of MMP-13-silenced MDA-MB-231 cells into nude mice femurs. RESULTS: MMP-13 was co-expressed by human breast tumour bone metastases with its activator MT1-MMP. MMP-13 was up-regulated in breast cancer cells after in vitro stimulation with IL-8 and was responsible for increased bone resorption and osteoclastogenesis, both of which were reduced by MMP inhibitors. We hypothesized that MMP-13 might be directly involved in the loop promoting pre-osteoclast differentiation and activity. We obtained further evidence for a direct role of MMP-13 in bone metastasis by a silencing approach: conditioned media from MDA-MB-231 after MMP-13 abrogation or co-cultivation of silenced cells with pre-osteoclast were unable to increase pre-osteoclast differentiation and resorption activity. MMP-13 activated pre-MMP-9 and promoted the cleavage of galectin-3, a suppressor of osteoclastogenesis, thus contributing to pre-osteoclast differentiation. Accordingly, MMP-13 abrogation in tumour cells injected into the femurs of nude mice reduced the differentiation of TRAP positive cells in bone marrow and within the tumour mass as well as bone erosion. CONCLUSIONS: These results indicate that within the inflammatory bone microenvironment MMP-13 production was up-regulated in breast tumour cells leading to increased pre-osteoclast differentiation and their subsequent activation

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO