Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions

Background: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. Results: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood parameters measured ten and fifteen hours, respectively, after each shift. The "speed-change" factor was significantly associated with mean heart cycle length (MCL, +7% per standard deviation increase in the factor score), heart rate variability (+16%), supraventricular ectopic beats (+39%), % neutrophils (+7%), % lymphocytes (-10%), red blood cell volume MCV (+1%), von Willebrand Factor (+9%), blood urea nitrogen (+7%), and protein C (-11%). The "crustal" factor (but not the "collapsed" source) was associated with MCL (+3%) and serum uric acid concentrations (+5%). Controlling for potential confounders had little influence on the effect estimates. Conclusion: PM2.5 originating from speed-changing traffic modulates the autonomic control of the heart rhythm, increases the frequency of premature supraventricular beats and elicits proinflammatory and pro-thrombotic responses in healthy young men. [Authors]

Secondary effects of catalytic diesel particulate filters: copper-induced formation of PCDD/Fs.

Potential risks of a secondary formation of polychlorinated dibenzodioxins/furans (PCDD/Fs) were assessed for two cordierite-based, wall-through diesel particulate filters (DPFs) for which soot combustion was either catalyzed with an iron- or a copper-based fuel additive. A heavy duty diesel engine was used as test platform, applying the eight-stage ISO 8178/4 C1 cycle. DPF applications neither affected the engine performance, nor did they increase NO, NO2, CO, and CO2 emissions. The latter is a metric for fuel consumption. THC emissions decreased by about 40% when deploying DPFs. PCDD/F emissions, with a focus on tetra- to octachlorinated congeners, were compared under standard and worst case conditions (enhanced chlorine uptake). The iron-catalyzed DPF neither increased PCDD/F emissions, nor did it change the congener pattern, even when traces of chlorine became available. In case of copper, PCDD/F emissions increased by up to 3 orders of magnitude from 22 to 200 to 12 700 pg I-TEQ/L with fuels of < 2, 14, and 110 microg/g chlorine, respectively. Mainly lower chlorinated DD/Fs were formed. Based on these substantial effects on PCDD/F emissions, the copper-catalyzed DPF system was not approved for workplace applications, whereas the iron system fulfilled all the specifications of the Swiss procedures for DPF approval (VERT).

EuroDia: a beta-cell gene expression resource.

Type 2 diabetes mellitus (T2DM) is a major disease affecting nearly 280 million people worldwide. Whilst the pathophysiological mechanisms leading to disease are poorly understood, dysfunction of the insulin-producing pancreatic beta-cells is key event for disease development. Monitoring the gene expression profiles of pancreatic beta-cells under several genetic or chemical perturbations has shed light on genes and pathways involved in T2DM. The EuroDia database has been established to build a unique collection of gene expression measurements performed on beta-cells of three organisms, namely human, mouse and rat. The Gene Expression Data Analysis Interface (GEDAI) has been developed to support this database. The quality of each dataset is assessed by a series of quality control procedures to detect putative hybridization outliers. The system integrates a web interface to several standard analysis functions from R/Bioconductor to identify differentially expressed genes and pathways. It also allows the combination of multiple experiments performed on different array platforms of the same technology. The design of this system enables each user to rapidly design a custom analysis pipeline and thus produce their own list of genes and pathways. Raw and normalized data can be downloaded for each experiment. The flexible engine of this database (GEDAI) is currently used to handle gene expression data from several laboratory-run projects dealing with different organisms and platforms. Database URL: http://eurodia.vital-it.ch.

SwissDock, a protein-small molecule docking web service based on EADock DSS.

Most life science processes involve, at the atomic scale, recognition between two molecules. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Docking programs have a wide range of applications ranging from protein engineering to drug design. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. A wiki and a forum are available to the community to promote interactions between users. The SwissDock web site is available online at http://www.swissdock.ch. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling community.

Quality of Web-based information on obsessive compulsive disorder.

BACKGROUND: The Internet is increasingly used as a source of information for mental health issues. The burden of obsessive compulsive disorder (OCD) may lead persons with diagnosed or undiagnosed OCD, and their relatives, to search for good quality information on the Web. This study aimed to evaluate the quality of Web-based information on English-language sites dealing with OCD and to compare the quality of websites found through a general and a medically specialized search engine. METHODS: Keywords related to OCD were entered into Google and OmniMedicalSearch. Websites were assessed on the basis of accountability, interactivity, readability, and content quality. The "Health on the Net" (HON) quality label and the Brief DISCERN scale score were used as possible content quality indicators. Of the 235 links identified, 53 websites were analyzed. RESULTS: The content quality of the OCD websites examined was relatively good. The use of a specialized search engine did not offer an advantage in finding websites with better content quality. A score ≥16 on the Brief DISCERN scale is associated with better content quality. CONCLUSION: This study shows the acceptability of the content quality of OCD websites. There is no advantage in searching for information with a specialized search engine rather than a general one. Practical implications: The Internet offers a number of high quality OCD websites. It remains critical, however, to have a provider-patient talk about the information found on the Web.

Homology modeling and metabolism prediction of human carboxylesterase-2 using docking analyses by GriDock: a parallelized tool based on AutoDock 4.0.

Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted to developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas less has been done to predict the activity of human hydrolases. The present study was undertaken to develop a computational approach able to predict the hydrolysis of novel esters by human carboxylesterase hCES2. The study involved first a homology modeling of the hCES2 protein based on the model of hCES1 since the two proteins share a high degree of homology (congruent with 73%). A set of 40 known substrates of hCES2 was taken from the literature; the ligands were docked in both their neutral and ionized forms using GriDock, a parallel tool based on the AutoDock4.0 engine which can perform efficient and easy virtual screening analyses of large molecular databases exploiting multi-core architectures. Useful statistical models (e.g., r (2) = 0.91 for substrates in their unprotonated state) were calculated by correlating experimental pK(m) values with distance between the carbon atom of the substrate's ester group and the hydroxy function of Ser228. Additional parameters in the equations accounted for hydrophobic and electrostatic interactions between substrates and contributing residues. The negatively charged residues in the hCES2 cavity explained the preference of the enzyme for neutral substrates and, more generally, suggested that ligands which interact too strongly by ionic bonds (e.g., ACE inhibitors) cannot be good CES2 substrates because they are trapped in the cavity in unproductive modes and behave as inhibitors. The effects of protonation on substrate recognition and the contrasting behavior of substrates and products were finally investigated by MD simulations of some CES2 complexes.

Quality of Web-based information on obsessive compulsive disorder.

BACKGROUND: The Internet is increasingly used as a source of information for mental health issues. The burden of obsessive compulsive disorder (OCD) may lead persons with diagnosed or undiagnosed OCD, and their relatives, to search for good quality information on the Web. This study aimed to evaluate the quality of Web-based information on English-language sites dealing with OCD and to compare the quality of websites found through a general and a medically specialized search engine. METHODS: Keywords related to OCD were entered into Google and OmniMedicalSearch. Websites were assessed on the basis of accountability, interactivity, readability, and content quality. The "Health on the Net" (HON) quality label and the Brief DISCERN scale score were used as possible content quality indicators. Of the 235 links identified, 53 websites were analyzed. RESULTS: The content quality of the OCD websites examined was relatively good. The use of a specialized search engine did not offer an advantage in finding websites with better content quality. A score ≥16 on the Brief DISCERN scale is associated with better content quality. CONCLUSION: This study shows the acceptability of the content quality of OCD websites. There is no advantage in searching for information with a specialized search engine rather than a general one. Practical implications: The Internet offers a number of high quality OCD websites. It remains critical, however, to have a provider-patient talk about the information found on the Web.

Fast docking using the CHARMM force field with EADock DSS.

The prediction of binding modes (BMs) occurring between a small molecule and a target protein of biological interest has become of great importance for drug development. The overwhelming diversity of needs leaves room for docking approaches addressing specific problems. Nowadays, the universe of docking software ranges from fast and user friendly programs to algorithmically flexible and accurate approaches. EADock2 is an example of the latter. Its multiobjective scoring function was designed around the CHARMM22 force field and the FACTS solvation model. However, the major drawback of such a software design lies in its computational cost. EADock dihedral space sampling (DSS) is built on the most efficient features of EADock2, namely its hybrid sampling engine and multiobjective scoring function. Its performance is equivalent to that of EADock2 for drug-like ligands, while the CPU time required has been reduced by several orders of magnitude. This huge improvement was achieved through a combination of several innovative features including an automatic bias of the sampling toward putative binding sites, and a very efficient tree-based DSS algorithm. When the top-scoring prediction is considered, 57% of BMs of a test set of 251 complexes were reproduced within 2 Å RMSD to the crystal structure. Up to 70% were reproduced when considering the five top scoring predictions. The success rate is lower in cross-docking assays but remains comparable with that of the latest version of AutoDock that accounts for the protein flexibility. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011.

MyHits: improvements to an interactive resource for analyzing protein sequences.

The MyHits web site (http://myhits.isb-sib.ch) is an integrated service dedicated to the analysis of protein sequences. Since its first description in 2004, both the user interface and the back end of the server were improved. A number of tools (e.g. MAFFT, Jacop, Dotlet, Jalview, ESTScan) were added or updated to improve the usability of the service. The MySQL schema and its associated API were revamped and the database engine (HitKeeper) was separated from the web interface. This paper summarizes the current status of the server, with an emphasis on the new services.

Ex-Vivo Ultransonographic Control Of Resection Margin During Partial Nephrectomy

Introduction & Objectives: Surgery remains the treatment of choice for localized renal cell neoplasia. While radical nephrectomy was long considered as gold standard, partial nephrectomy (PN) has widened its indications over the past twodecades and has shown oncological results equivalent to radical nephrectomy for small tumors. Moreover, it is considered superior to radical nephrectomy in terms of non-cancer related mortality. The role of negative surgical margin has been widely debated. Intraoperative frozen section analysis has been shown to be unreliable, expensive, time-consuming and not well correlated to final pathology. The goal of the present study was to assess the correlation of intraoperative exvivo ultrasonographic (US) evaluation of resection margin to definitive pathology in patients undergoing PN.Materials & Methods: An observational study was carried out in ours 2 institutions from February 2008 to October 2010. Patients undergoing PN for T1-T2 renal tumors were included. Ex vivo US evaluation was performed. Considering availability of US engine, not all consecutive eligible patients were included. PN was undertaken either by open surgery or laparoscopic access in a standardized technique. The "minimal healthy tissue margin" technique was applied. Once resected, the specimen was kept in a saline solution and US determination of tumor margins was performed. Sequential images were captured in order to evaluate the whole capsule.Results: Twenty-two patients (9 women, age 63±11 years[46-78]) were included in the present analysis. Open or laparoscopic PN was performed in 19 and 3 patients, respectively. Intraoperative ex-vivo US showed negative surgical margin in all cases except one, needing a complementary renal parenchyma resection. US duration ranged from 1 to 4 minutes, with a median time of 1 minute. Definitive histological analysis confirmed the presence of 3 angiomyolipoma, 15 clear cell carcinoma (11 pT1a,3 pT1b,1 pT2), 3 chromophobe carcinoma (1 pT1a,1 pT1b,1 pT2) and 1 pT1a type II papillary tumor. Mean tumor size was 3,4±2.1 cm [0,6-7,2]. Final pathology revealed R0 margins in all cases.Conclusions: Intraoperative ex-vivo US evaluation of resection margin in patients undergoing PN is feasible, time-efficient, well correlated to definitive pathological examination, and should be evaluated in further prospective trials.

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted b diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

Phenotip - a web-based instrument to help diagnosing fetal syndromes antenatally.

Prenatal ultrasound can often reliably distinguish fetal anatomic anomalies, particularly in the hands of an experienced ultrasonographer. Given the large number of existing syndromes and the significant overlap in prenatal findings, antenatal differentiation for syndrome diagnosis is difficult. We constructed a hierarchic tree of 1140 sonographic markers and submarkers, organized per organ system. Subsequently, a database of prenatally diagnosable syndromes was built. An internet-based search engine was then designed to search the syndrome database based on a single or multiple sonographic markers. Future developments will include a database with magnetic resonance imaging findings as well as further refinements in the search engine to allow prioritization based on incidence of syndromes and markers.

Cation Transport Coupled to ATP Hydrolysis By the (Na, K)-ATPase : an integrated, animated model

An Adobe (R) animation is presented for use in undergraduate Biochemistry courses, illustrating the mechanism of Na+ and K+ translocation coupled to ATP hydrolysis by the (Na, K)-ATPase, a P-2c-type ATPase, or ATP-powered ion pump that actively translocates cations across plasma membranes. The enzyme is also known as an E-1/E-2-ATPase as it undergoes conformational changes between the E-1 and E-2 forms during the pumping cycle, altering the affinity and accessibility of the transmembrane ion-binding sites. The animation is based on Horisberger's scheme that incorporates the most recent significant findings to have improved our understanding of the (Na, K)-ATPase structure function relationship. The movements of the various domains within the (Na, K)-ATPase alpha-subunit illustrate the conformational changes that occur during Na+ and K+ translocation across the membrane and emphasize involvement of the actuator, nucleotide, and phosphorylation domains, that is, the "core engine" of the pump, with respect to ATP binding, cation transport, and ADP and P-i release.

A numeric model to simulate solar individual ultraviolet exposure.

Exposure to solar ultraviolet (UV) light is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors. Individual exposure data remain scarce and development of alternative assessment methods is greatly needed. We developed a model simulating human exposure to solar UV. The model predicts the dose and distribution of UV exposure received on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a rendering engine that estimates the solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by each triangle was calculated, taking into account reflected, direct and diffuse radiation, and shading from other body parts. Dosimetric measurements (n = 54) were conducted in field conditions using a foam manikin as surrogate for an exposed individual. Dosimetric results were compared to the model predictions. The model predicted exposure to solar UV adequately. The symmetric mean absolute percentage error was 13%. Half of the predictions were within 17% range of the measurements. This model provides a tool to assess outdoor occupational and recreational UV exposures, without necessitating time-consuming individual dosimetry, with numerous potential uses in skin cancer prevention and research.

Growth and demise of Permian biogenic chert along northwest Pangea: evidence for end-Permian collapse of thermohaline circulation

The Permian Chert Event (PCE) was a 30 Ma long episode of unusual chert accumulation along the northwest margin of Pangea, and possibly worldwide. The onset of the PCE occurred at about the Sakmarian-Artinskian boundary in the Sverdrup Basin, Canadian Arctic, where it coincides with a maximum flooding event, the ending of high-frequency/high-amplitude shelf cyclicity, the onset of massive biogenic chert deposition in deep-water distal areas, and a long-term shift from warm- to cool-water carbonate sedimentation in shallow-water proximal areas. A similar and coeval shift is observed from the Barents Sea to the northwestern USA. A landward and southward expansion of silica factories occurred during the Middle and Late Permian at which time warm-water carbonate producers disappeared completely from the northwest margin of Pangea. Biotically impoverished and increasingly narrow cold-water carbonate factories (characterised by non-cemented bioclasts of sponges, bryozoans, echinoderms and brachiopods) were then progressively replaced by silica factories. By Late Permian time, little carbonate sediments accumulated in the Barents Sea and in the Sverdrup Basin. where the deep- to shallow-water sedimentary spectrum was occupied by siliceous sponge spicules. By that time, biogenic silica sedimentation was common throughout the world. Silica factories collapsed in the Late Permian, abruptly bringing the PCE to an end. In northwest Pangea, the end- Permian collapse of the PCE was associated with a major transgression and with a return to much warmer oceanic and continental climatic conditions. Chert deposition resumed in the distal oceanic areas during the early Middle Triassic (Anisian) after a 8-10 Ma interruption (Early Triassic Chert Gap). The conditions necessary for the onset, expansion and zenith of the PCE were provided by the thermohaline circulation of nutrient-rich cold waters along the northwestern and western margin of Pangea, and possibly throughout the world oceans. These conditions provided an efficient transportation mechanism that constantly replenished the supply of silica in the area, created a nutrient- and oxygen-rich environment favouring siliceous biogenic productivity. established cold sea-floor conditions, hindering silica dissolution, while increasing calcium carbonate solubility, and provided conditions adverse to organic and inorganic carbonate production, The northwest margin of Pangea was, for nearly 30 Ma. bathed by cold waters presumably derived from the seasonal melting of northern sea ice, the assumed engine for thermohaline circulation. This process started near the Sakmarian-Artinskian boundary. intensified throughout Middle and Late Permian time and ceased suddenly in latest Permian time, It led to oceanic conditions much colder than normally expected from the palaeolatitudes. and the influence of cold northerly-derived water was felt as far south southern Nevada. The demise of silica factories was caused by the rapid breakdown of these conditions and the establishment of a much warmer marine environment accompanied by sluggish circulation and perhaps a reduced input of dissolved silica to the ocean. Complete thawing of northern sea ice would have ended thermohaline circulation and led to warm and sluggish oceanic conditions inimical to the production. accumulation and preservation of biogenic silica.