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Background: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021., Methods: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed., Results: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases., Conclusions: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC 50s ) in the sub-micromolar and low micromolar range., (© 2022. The Author(s).)

Methylmalonic acidemia (MMA) is an inborn error of metabolism mostly caused by mutations in the mitochondrial methylmalonyl-CoA mutase gene (MMUT). MMA patients suffer from frequent episodes of metabolic decompensation, which can be life threatening. To mimic both the dietary restrictions and metabolic decompensation seen in MMA patients, we developed a novel protein-controlled diet regimen in a Mmut deficient mouse model of MMA and demonstrated the therapeutic benefit of mLB-001, a nuclease-free, promoterless recombinant AAV GeneRideTM vector designed to insert the mouse Mmut into the endogenous albumin locus via homologous recombination. A single intravenous administration of mLB-001 to neonatal or adult MMA mice prevented body weight loss and mortality when challenged with a high protein diet. The edited hepatocytes expressed functional MMUT protein and expanded over time in the Mmut deficient mice, suggesting a selective growth advantage over the diseased cells. In mice with a humanized liver, treatment with a human homolog of mLB-001 resulted in site-specific genome editing and transgene expression in the transplanted human hepatocytes. Taken together, these findings support the development of hLB-001 that is currently in clinical trials in pediatric patients with severe forms of MMA., Competing Interests: The authors are/were employees of LogicBio Therapeutics. LogicBio has filed pending patent applications published as WO2020/032986 (pertaining to non-disruptive gene therapy for the treatment of MMA) and WO2020/214582 (pertaining to monitoring gene therapy). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The aim of this study was to assess current French practices in the management of patients with advanced epithelial ovarian cancer., Method: a 58-question electronic survey was distributed anonymously to the members of the SFOG (French Society of Gynaecological Oncology), GINECO-ARCAGY (National Investigators Group for Ovarian and Breast Cancer Studies in France) and FRANCOGYN (French research group in oncological and gynaecological surgery). Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed., Results: a total of 107 participants responded to emailed surveys. Most of the respondents were obstetrician-gynaecologists (37.4%), surgical oncologists (34.6%) and medical oncologists (17.8%). According to most (76.8%) participants, less than 50% of patients were eligible for primary debulking surgery (PDS). The LION study criteria were applied in 69.5% of cases during PDS and 39% after chemotherapy. The timing of BRCA testing was very heterogeneous and ranged from 1 to 6 months. The use of bevacizumab as an adjuvant schedule was lower in cases of no residual disease (for 54.5% of respondents) compared to cases of residual disease (for 63.6% of respondents). In cases of BRCA1-2 mutations, olaparib was given by 75.8-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases., Conclusion: this survey provides an extensive and a unique review of current French practices in the management of patients with advanced epithelial ovarian cancer in 2021.

Farmers' market implementation holds promise for increasing access to healthy foods. Although rarely measured, purchase data constitute an intermediate outcome between food environment and actual consumption. In a study conducted with two seasonal Fruits and Vegetables (FV) stands in a disadvantaged area of Montréal (Canada), we analysed how accessibility, perception, and mobility-related factors were associated with FV purchase. This analysis uses a novel measure of FV purchasing practices based on sales data obtained from a mobile application. A 2016 survey collected information on markets' physical access, perceived access to FV in the neighbourhood, usual FV consumption and purchases. Multivariate models were used to analyse three purchasing practice indicators: number of FV portions, FV variety and expenditures. Average shoppers purchased 12 FV portions of three distinct varieties and spent 5$. Shoppers stopping at the market on their usual travel route spent less ( p = 0.11), bought fewer portions ( p = 0.03) and a lesser FV variety ( p < 0.01). FV stands may complement FV dietary intake. Individuals for whom the market is on their usual travel route might make more frequent visits and, therefore, smaller purchases. The novel data collection method allowed analysis of multiple purchase variables, is precise and easy to apply at unconventional points of sales and could be transposed elsewhere.

Aim: To describe the clinical features and etiologies of upper limb venous thrombosis (ULVT)., Methods: All patients with a clinically suspected ULVT, were included retrospectively from January to December 2016. Diagnosis of ULVT was based on doppler-ultrasonography. Clinical features, topography and symptomatic pulmonary embolism (PE) were analyzed. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative value (NPV) of clinical symptoms leading to ULVT suspicion were estimated by comparing patients with and without ULVT., Results: Among 488 patients with a suspected ULVT, 160 were diagnosed with ULVT, including, 80 with deep venous thrombosis (DVT) and 80 with superficial venous thrombosis (SVT). Symptomatic PE was found in 2.5 % of cases (n=4). None of the clinical symptoms of ULVT had a sensitivity greater than 40 %. For DVT, presence of superior vena cava syndrome had a 100 % PPV, 71.6 % NPV and 100 % Sp. For SVT, the presence of an cord-like induration had a 85.7 % PPV, 75.3 % NPV and 98.4 % Sp. An endovenous device was present in 87.5 % of DVT and 97.5 % of SVT cases. Malignant hemopathy was found in 43.8 % and 31.3 % of cases of DVT and SVT, respectively. Sepsis and solid neoplasia were present in 25 % and 15 % of cases of ULVT, respectively. Peripherally inserted central catheter or implantable sites were present in 40 % and 17.5 % of DVT patients. No solid neoplasia, hematological malignancy or thrombophilia were diagnosed in patients with ULVT., Conclusion: An endovenous device was involved in 92.5 % of cases of ULVT. The prevalence of symptomatic PE was low. Hematological malignancies, sepsis and neoplasia were the most common conditions present in patients with ULVT., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Alternative food sources (AFS) such as local markets in disadvantaged areas are promising strategies for preventing chronic disease and reducing health inequalities. The present study assessed how sociodemographic characteristics, physical access and fruit and vegetable (F&V) consumption are associated with market use in a newly opened F&V market next to a subway station in a disadvantaged neighbourhood., Design: Two cross-sectional surveys were conducted among adults: (i) on-site, among shoppers who had just bought F&V and (ii) a telephone-based population survey among residents living within 1 km distance from the market., Setting: One neighbourhood in Montreal (Canada) with previously limited F&V offerings., Subjects: Respectively, 218 shoppers and 335 residents completed the on-site and telephone-based population surveys., Results: Among shoppers, 23 % were low-income, 56 % did not consume enough F&V and 54 % did not have access to a car. Among all participants living 1 km from the market (n 472), market usage was associated (OR; 95 % CI) with adequate F&V consumption (1·86; 1·10, 3·16), living closer to the market (for distance: 0·86; 0·76, 0·97), having the market on the commute route (2·77; 1·61, 4·75) and not having access to a car (2·96; 1·67, 5·26)., Conclusions: When implemented in strategic locations such as transport hubs, AFS like F&V markets offer a promising strategy to improve F&V access among populations that may be constrained in their food acquisition practices, including low-income populations and those relying on public transportation.

Background: Since public transit infrastructure affects road traffic volumes and influences transportation mode choice, which in turn impacts health, it is important to estimate the alteration of the health burden linked with transit policies., Objective: We quantified the variation in health benefits and burden between a business as usual (BAU) and a public transit (PT) scenarios in 2031 (with 8 and 19 new subway and train stations) for the greater Montreal region., Method: Using mode choice and traffic assignment models, we predicted the transportation mode choice and traffic assignment on the road network. Subsequently, we estimated the distance travelled in each municipality by mode, the minutes spent in active transportation, as well as traffic emissions. Thereafter we estimated the health burden attributed to air pollution and road traumas and the gains associated with active transportation for both the BAU and PT scenarios., Results: We predicted a slight decrease of overall trips and kilometers travelled by car as well as an increase of active transportation for the PT in 2031 vs the BAU. Our analysis shows that new infrastructure will reduce the overall burden of transportation by 2.5 DALYs per 100,000 persons. This decrease is caused by the reduction of road traumas occurring in the inner suburbs and central Montreal region as well as gains in active transportation in the inner suburbs., Conclusion: Based on the results of our study, transportation planned public transit projects for Montreal are unlikely to reduce drastically the burden of disease attributable to road vehicles and infrastructures in the Montreal region. The impact of the planned transportation infrastructures seems to be very low and localized mainly in the areas where new public transit stations are planned., (Copyright © 2017 Elsevier Inc. All rights reserved.)

TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein-protein interaction represents a putative cancer target, but no small-molecule inhibitors have been published for this challenging interface. Herein, the structure-enabled design and synthesis of a constrained peptide inhibitor of TLE1 is reported. The design features the introduction of a four-carbon-atom linker into the peptide epitope found in many TLE1 binding partners. A concise synthetic route to a proof-of-concept peptide, cycFWRPW, has been developed. Biophysical testing by isothermal titration calorimetry and thermal shift assays showed that, although the constrained peptide bound potently, it had an approximately five-fold higher K d than that of the unconstrained peptide. The co-crystal structure suggested that the reduced affinity was likely to be due to a small shift of one side chain, relative to the otherwise well-conserved conformation of the acyclic peptide. This work describes a constrained peptide inhibitor that may serve as the basis for improved inhibitors., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The members of the NSD subfamily of lysine methyl transferases are compelling oncology targets due to the recent characterization of gain-of-function mutations and translocations in several hematological cancers. To date, these proteins have proven intractable to small molecule inhibition. Here, we present initial efforts to identify inhibitors of MMSET (aka NSD2 or WHSC1) using solution phase and crystal structural methods. On the basis of 2D NMR experiments comparing NSD1 and MMSET structural mobility, we designed an MMSET construct with five point mutations in the N-terminal helix of its SET domain for crystallization experiments and elucidated the structure of the mutant MMSET SET domain at 2.1 Å resolution. Both NSD1 and MMSET crystal systems proved resistant to soaking or cocrystallography with inhibitors. However, use of the close homologue SETD2 as a structural surrogate supported the design and characterization of N-alkyl sinefungin derivatives, which showed low micromolar inhibition against both SETD2 and MMSET.

This natural experiment examines the effect of a public bicycle share program on cognitions and investigates the moderating influence of socioeconomic status on this effect. Two cross-sectional population-based surveys were conducted. Intention and self-efficacy to use the public bicycle share program were assessed by questionnaire. A difference-in-differences approach was adopted using logistic regression analyses. A significant effect of the public bicycle share program was observed on intention (exposure × time; odds ratio = 3.41; 95% confidence interval: 1.50-7.73) and self-efficacy (exposure; odds ratio = 1.61; 95% confidence interval: 1.28-2.01). A positive effect on intention was observed among individuals with low income (exposure × time; odds ratio = 27.85; 95% confidence interval: 2.51-309.25). Implementing a public bicycle share program is associated with increases in intention and self-efficacy for public bicycle share use, although some social inequalities persist., (© The Author(s) 2014.)

Background: Favorable public opinion and support for policies are essential to favor the sustainability of environmental interventions. This study examined public perceptions and support for active living policies associated with implementing a public bicycle share program (PBSP)., Methods: Two cross-sectional population-based telephone surveys were conducted in 2009 and 2010 among 5011 adults in Montréal, Canada. Difference-in-differences analyses tested the impact of the PBSP on negative perceptions of the impact of the PBSP on the image of the city, road safety, ease of traveling, active transportation, health, and resistance to policies., Results: People living closer to docking stations were less likely to have negative perceptions of the effect of the PBSP on the image of the city (OR = 0.5; 95% CI, 0.4-0.8) and to be resistant to policies (OR = 0.8; 95% CI, 0.6-1.0). The likelihood of perceiving negative effects on road safety increased across time (OR = 1.4; 95% CI, 1.2-1.8). Significant interactions were observed for perceptions of ease of traveling (OR = 0.5; 95% CI, 0.4-0.8), active transportation (OR = 0.6; 95% CI, 0.4-1.0), and health (OR = 0.6; 95% CI, 0.4-0.8): likelihood of negative perceptions decreased across time among people exposed., Conclusion: Findings indicate that negative perceptions were more likely to abate among those living closer to the PBSP.

The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 (BAZ2-ICR) of the BAZ2A/B bromodomains through rapid optimization of a weakly potent starting point. A key feature of the presented inhibitors is an intramolecular aromatic stacking interaction that efficiently occupies the shallow bromodomain pockets. 13 represents an excellent chemical probe for functional studies of the BAZ2 bromodomains in vitro and in vivo.

Objectives: 1) To describe grassroots projects aimed at the built environment and associated with active transportation on the Island of Montreal; and 2) to examine associations between the number of projects and indicators of neighbourhood material and social deprivation and the built environment., Method: We identified funding agencies and community groups conducting projects on built environments throughout the Island of Montreal. Through website consultation and a snowballing procedure, we inventoried projects that aimed at transforming built environments and that were carried out by community organizations between January 1, 2006, and November 1, 2010. We coded and validated information about project activities and created an interactive map using Geoclip software. Correlational analyses quantified associations between number of projects, neighbourhood characteristics and deprivation., Results: A total of 134 community organizations were identified, and 183 grassroots projects were inventoried. A large number of projects were aimed at increasing awareness of/improving active or public transportation (n=95), improving road safety (n=84) and enhancing neighbourhood beautification and greening (n=69). The correlation between the presence of projects and the extent of neighbourhood material deprivation was small (Kendall's t=0.26, p&lt;0.001), but in areas with greater social deprivation there were more projects (Kendall's t=0.38, p&lt;0.001). Larger numbers of projects were also associated with the presence of more extensive land-use mix (Kendall's t=0.23, p&lt;0.001) and a greater proportion of road intersections with injured pedestrians, cyclists and motor vehicle users (Kendall's t=0.43, p&lt;0.001)., Conclusion: There is significant community mobilization around built environments and active transportation. Investigations of the implementation processes and impacts are warranted.

Objective: This study aimed to estimate the impact of implementing a public bicycle share program (PBSP) on the likelihood of self-reported collisions and near misses between cyclists and motor vehicles among cyclists living in Montreal., Methods: A repeated cross sectional design was used. Surveys were conducted at the launch of the PBSP, at the end of the first and second seasons of implementation. Logistic regression estimated changes in the likelihood of reporting collisions or near misses., Results: There was no evidence of a change in likelihood of reporting a collision or near miss after implementing the PBSP. PBSP users were not at a greater risk of reporting a collision (OR=1.53, 95% CI: 0.77-3.02) or near miss (OR=1.37, 95% CI: 0.94-1.98), although confidence intervals were wide. The number of days of cycling per week was associated with collisions (OR=1.27, 95% CI: 1.17-1.39) and near misses (OR=1.34, 95% CI: 1.26-1.42)., Conclusions: There was no evidence of a change in the likelihood of reporting collisions or near misses in Montreal between the implementation of the PBSP and the end of the second season. Time spent cycling was associated with reporting a collision or near miss., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: This study estimated the modal shift associated with the implementation of a public bicycle share program in Montreal, Canada., Methods: A population-based sample of adults participated in two cross sectional telephone surveys. Self-reported travel behaviors were collected at the end of the first (fall 2009) and second (fall 2010) season of implementation. The sample included 2502 (Mean age=47.8 years, 61.8% female), and 2509 (Mean age=48.9 years, 59.0% female) adult respondents in each survey., Results: The estimated modal shift associated with the implementation of the PBSP from motor vehicle use to walking, cycling, and public transportation was 6483 and 8023 trips in 2009 and 2010. This change represents 0.34% and 0.43% of all motor vehicle trips in Montreal., Conclusions: The implementation of a PBSP was associated with a shift toward active transportation. The modal shift was complex and not simply the result of a discrete shift from one mode to another. Promotion of active transportation should encourage integration of multiple active transportation modes to better reflect people's actual transportation behaviors.

Objectives: We examined associations between residential exposure to BIXI (BIcycle-taXI)-a public bicycle share program implemented in Montreal, Quebec, in 2009, which increases accessibility to cycling by making available 5050 bicycles at 405 bicycle docking stations-and likelihood of cycling (BIXI and non-BIXI) in Montreal over the first 2 years of implementation., Methods: Three population-based samples of adults participated in telephone surveys. Data collection occurred at the launch of the program (spring 2009), and at the end of the first (fall 2009) and second (fall 2010) seasons of implementation. Difference in differences models assessed whether greater cycling was observed for those exposed to BIXI compared with those not exposed at each time point., Results: We observed a greater likelihood of cycling for those exposed to the public bicycle share program after the second season of implementation (odds ratio = 2.86; 95% confidence interval = 1.85, 4.42) after we controlled for weather, built environment, and individual variables., Conclusions: The implementation of a public bicycle share program can lead to greater likelihood of cycling among persons living in areas where bicycles are made available.

Active living is a broad conceptualization of physical activity that incorporates domains of exercise; recreational, household, and occupational activities; and active transportation. Policy makers develop and implement a variety of transportation policies that can influence choices about how to travel from one location to another. In making such decisions, policy makers act in part in response to public opinion or support for proposed policies. Measures of the public's support for policies aimed at promoting active transportation can inform researchers and policy makers. This study examined the internal consistency, and concurrent and discriminant validity of a newly developed measure of the public's support for policies for active living in transportation (PAL-T). A series of 17 items representing potential policies for promoting active transportation was generated. Two samples of participants (n = 2,001 and n = 2,502) from Montreal, Canada, were recruited via random digit dialling. Analyses were conducted on the combined data set (n = 4,503). Participants were aged 18 through 94 years (58% female). The concurrent and discriminant validity of the PAL-T was assessed by examining relationships with physical activity and smoking. To explore the usability of the PAL-T, predicted scale scores were compared to the summed values of responses. Results showed that the internal consistency of the PAL-T was 0.70. Multilevel regression demonstrated no relationship between the PAL-T and smoking status (p > 0.05) but significant relationships with utilitarian walking (p < 0.05) and cycling (p < 0.01) for at least 30 minutes on 5 days/week. The PAL-T has acceptable internal consistency and good concurrent and discriminant validity. Measuring public opinion can inform policy makers and support advocacy efforts aimed at making built environments more suitable for active transportation while allowing researchers to examine the antecedents and consequences of public support for policies.

The Kulinkovich-de Meijere reaction between an unsaturated Grignard reagent and a chiral amide takes place with a high trans stereoselectivity and provides a convenient access to non-racemic trans cyclopropylamines. These compounds are transformed in four steps into the corresponding N-protected β,γ-methano-GABA derivatives, which are obtained for the first time in enantiomerically pure form. The corresponding transformations of the cis cyclopropylamine adducts are also described.

Background: Cycling contributes to physical activity and health. Public bicycle share programs (PBSPs) increase population access to bicycles by deploying bicycles at docking stations throughout a city. Minimal research has systematically examined the prevalence and correlates of PBSP use., Purpose: To determine the prevalence and correlates of use of a new public bicycle share program called BIXI (name merges the word BIcycle and taXI) implemented in May 2009 in Montreal, Canada., Methods: A total of 2502 adults were recruited to a telephone survey in autumn 2009 via random-digit dialing according to a stratified random sampling design. The prevalence of BIXI bicycle use was estimated. Multivariate logistic regression allowed for identification of correlates of use. Data analysis was conducted in spring and summer 2010., Results: The unweighted mean age of respondents was 47.4 (SD=16.8) years and 61.4% were female. The weighted prevalence for use of BIXI bicycles at least once was 8.2%. Significant correlates of BIXI bicycle use were having a BIXI docking station within 250 m of home, being aged 18-24 years, being university educated, being on work leave, and using cycling as the primary mode of transportation to work., Conclusions: A newly implemented public bicycle share program attracts a substantial fraction of the population and is more likely to attract younger and more educated people who currently use cycling as a primary transportation mode., (Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this article is to describe a novel approach for understanding the subjective experience of being a pedestrian in urban settings. In so doing, we take into account the "experience of the body in movement" as described in different theories and according to different methods, and develop a tool to allow citizens and urban planners to exchange ideas about how to make cities more walkable. Finally, we present the adaptation of the approach for use in public health and provide a rationale for its more widespread use in place and health research., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A chiral polynuclear Gd complex derived from Gd(O(i)Pr)(3) and FujiCAPO (2 or 3) catalytically generated Gd enolates through two distinct methods; transmetalation from enol silyl ethers and conjugate addition of cyanide to alpha,beta-unsaturated N-acyl pyrroles. These chiral enolates can be enantioselectively protonated by a proton in an asymmetric environment in the polynuclear catalyst. Thus, catalytic enantioselective protonation of enol silyl ethers was promoted by the Gd catalyst (5-10 mol %) in the presence of a stoichiometric amount of 2,6-dimethylphenol. Kinetic studies and dependencies of the enantioselectivity on the silyl group structure and the proton source suggest that the reaction proceeds through a Gd enolate generated through transmetalation. Moreover, the same Gd complex (5-10 mol %) promoted conjugate addition of a cyanide-enantioselective protonation sequential reaction from alpha,beta-unsaturated N-acyl pyrroles. Because Gd isocyanide was determined to be the active nucleophile in the conjugate addition catalyzed by the Gd complex, enantioselective protonation likely proceeded through a Gd enolate in this case as well. The products are versatile dual functional chiral building blocks for organic synthesis.

The effect of carbon is subtle but sweet: The flexible C-linkage in the newly synthesised C-glycosyl mimetic, Manalpha(1,6)-C-ManalphaOPh allows OH--pi bonding, both in the gas phase and in aqueous solution. This interaction is absent in the O-linked disaccharide (see figure).The intrinsic conformational preference of a newly synthesised glycomimetic, the C-linked disaccharide Manalpha(1,6)-C-ManalphaOPh (1), has been determined in the gas phase at about 10 K by infrared ion dip spectroscopy coupled with density functional theory and ab initio calculations, and compared with its dynamical conformation in aqueous solution at 298 K by NMR spectroscopy. Comparisons are also made between these conformations and those of the corresponding O-linked disaccharide 2 in the gas phase and the C-linked disaccharide Manalpha(1,6)-C-ManalphaOMe (3) in the gas phase and in aqueous solution. The C- and O-linked disaccharides 1 and 2 present quite distinct conformational preferences in the gas phase: inter-glycosidic hydrogen bonding, seen in one of the two conformers populated in 2, is not seen in 1 which adopts a conformation (not populated in 2) with glycosidic dihedral angles (phi, psi, omega) of -72 degrees , 52 degrees and 66 degrees ; supported in part by an OH--pi hydrogen bond. This conformer is also strongly populated in an aqueous solution of 1 (and very weakly, of 3) together with a second conformer, with dihedral angles (phi, psi, omega) of about -60 degrees , 180 degrees and 60 degrees , not seen in the gas phase but by far the dominant conformer in an aqueous solution of 3. The C-disaccharide 1 was tested as a potential inhibitor, but displayed no significant inhibitory activity against Jack Bean alpha-mannosidase.

The title compound, C(21)H(26)O(10)S, was synthesized in a single step from mannose penta-acetate. The mol-ecular structure confirms the α configuration of the anomeric thioaryl substituent. Spectroscopic and melting-point data obtained for the title compound are in disagreement with those previously reported, indicating the previously reported synthesis [Durette & Shen (1980 ▶). Carbohydr. Res. 81, 261-274] to be erroneous. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds.

The title compound, C(40)H(31)NO(11)S·0.53CH(2)Cl(2)·0.38C(4)H(10)O, was synthesized in two steps from mannose penta-acetate and single crystals were grown by slow evaporation. The structure was determined by single-crystal X-ray diffraction, confirming the α-configuration of the anomeric thioaryl substituent. The asymmetric unit contains two crystallographically distinct mol-ecules of the carbohydrate. The central pyran-ose rings of these are geometrically similar, but there are differences in the orientations of the benzoate substituents.

At point of use generation of synthetically useful quantities of hydrogen peroxide in a non-optimized sono-electrochemical cell is reported. Proof-of-concept of the use of this procedure for green synthesis is given through the oxidation of benzonitrile to benzamide with yields similar to those obtained via bulk chemical synthesis.

The electrochemical oxidation of tris(4-bromophenyl)amine in the presence of 2,6-lutidine is examined in acetonitrile. Voltammetric and spectroscopic investigations suggest that the electrogenerated triaryl aminium radical cation oxidizes 2,6-lutidine in an EC' mechanism, and an equilibrium constant for this homogeneous electron transfer is estimated. The mediated oxidation of a protected phenyl selenoglycoside by this reaction mixture is studied by the use of electrochemical ESR, employing a tubular flow cell, and signal intensity data is found to be consistent with the proposed mechanism, allowing the determination of kinetic parameters by computational simulation. Products of the mediated glycoside oxidation are determined by proton NMR and mass spectrometry.

This paper describes the Québec experience in the design and implementation of occupational health programs in the workplace. To begin with, a brief overview of the historical context and organisational framework of occupational health are presented. Next, each of the phases involved in the design of occupational health programs is described: identification of workers' health and safety problems, selection of action priorities, and program design, implementation and evaluation.... In the end, the roles and responsibilities of the doctors, nurses and industrial hygienists generally involved in these multidisciplinary teams are presented.