A road map toward a globally harmonized approach for occupational health surveillance and epidemiology in nanomaterial workers

OBJECTIVE: Few epidemiological studies have addressed the health of workers exposed to novel manufactured nanomaterials. The small current workforce will necessitate pooling international cohorts. METHOD: A road map was defined for a globally harmonized framework for the careful choice of materials, exposure characterization, identification of study populations, definition of health endpoints, evaluation of appropriateness of study designs, data collection and analysis, and interpretation of the results. RESULTS: We propose a road map to reach global consensus on these issues. The proposed strategy should ensure that the costs of action are not disproportionate to the potential benefits and that the approach is pragmatic and practical. CONCLUSIONS: We should aim to go beyond the collection of health complaints, illness statistics, or even counts of deaths; the manifestation of such clear endpoints would indicate a failure of preventive measures.

Percutaneous drainage versus emergency cholecystectomy for the treatment of acute cholecystitis in critically ill patients: does it matter?

Background The aim if this study was to compare percutaneous drainage (PD) of the gallbladder to emergency cholecystectomy (EC) in a well-defined patient group with sepsis related to acute calculous/acalculous cholecystitis (ACC/AAC).Methods Between 2001 and 2007, all consecutive patients of our ICU treated by either PD or EC were retrospectively analyzed. Cases were collected from a prospective database. Percutaneous drainage was performed by a transhepatic route and EC by open or laparoscopic approach. Patients' general condition and organ dysfunction were assessed by two validated scoring systems (SAPS II and SOFA, respectively). Morbidity, mortality, and long-term outcome were systematically reviewed and analyzed in both groups.Results Forty-two patients [median age = 65.5 years (range = 32-94)] were included; 45% underwent EC (ten laparoscopic, nine open) and 55% PD (n = 23). Both patient groups had similar preoperative characteristics. Percutaneous drainage and EC were successful in 91 and 100% of patients, respectively. Organ dysfunctions were similarly improved by the third postoperative/postdrainage days. Despite undergoing PD, two patients required EC due to gangrenous cholecystitis. The conversion rate after laparoscopy was 20%. Overall morbidity was 8.7% after PD and 47% after EC (P = 0.011). Major morbidity was 0% after PD and 21% after EC (P = 0.034). The mortality rate was not different (13% after PD and 16% after EC, P = 1.0) and the deaths were all related to the patients' preexisting disease. Hospital and ICU stays were not different. Recurrent symptoms (17%) occurred only after ACC in the PD group.Conclusions In high-risk patients, PD and EC are both efficient in the resolution of acute cholecystitis sepsis. However, EC is associated with a higher procedure-related morbidity and the laparoscopic approach is not always possible. Percutaneous drainage represents a valuable intervention, but secondary cholecystectomy is mandatory in cases of acute calculous cholecystitis.

Initial and Extended Use of Femoral Versus Nonfemoral Double-Lumen Vascular Catheters and Catheter-Related Infection During Continuous Renal Replacement Therapy.

BACKGROUND: The risk of catheter-related infection or bacteremia, with initial and extended use of femoral versus nonfemoral sites for double-lumen vascular catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Critically ill patients on CRRT in a combined intensive care unit of a tertiary institution. FACTOR: Femoral versus nonfemoral venous DLVC placement. OUTCOMES: Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI). MEASUREMENTS: CRCOL/CRBSI rates expressed per 1,000 catheter-days. RESULTS: We studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405 single-site only DLVC users, 82% versus 18% received exclusively 419 femoral versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC indwelling duration was 6±4 versus 7±5 days (P=0.03). Corresponding CRCOL and CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P=0.8) and 1.2 versus 3.5 events (P=0.3), respectively. Overall, 96 patients with extended CRRT received femoral-site insertion first with subsequent site change, including 53 femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such approaches (P=0.7 and P=0.9, respectively). On multivariate analysis, CRCOL risk was higher in patients older than 65 years and weighing >90kg (ORs of 2.1 and 2.2, respectively; P<0.05). This association between higher weight and greater CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other covariates, including initial or specific DLVC site, guidewire exchange versus new venipuncture, and primary versus secondary DLVC placement, did not significantly affect CRCOL rates. LIMITATIONS: Nonrandomized retrospective design and single-center evaluation. CONCLUSIONS: CRCOL and CRBSI rates in patients on CRRT are low and not influenced significantly by initial or serial femoral catheterizations with guidewire exchange or new venipuncture. CRCOL risk is higher in older and heavier patients, the latter especially so with femoral sites.

Continuous electroencephalographic monitoring in critically ill patients with central nervous system infections.

OBJECTIVES: To determine the prevalence, predictors, and clinical significance of electrographic seizures (ESz) and other continuous electroencephalographic monitoring findings in critically ill patients with central nervous system infections. DESIGN: Retrospective cohort study. SETTING: Eighteen-bed neurocritical care unit. PATIENTS: We identified 42 consecutive patients with primary central nervous system infection (viral, 27 patients [64%]; bacterial, 8 patients [18%]; and fungal or parasitic, 7 patients [17%]) who underwent continuous electroencephalographic monitoring between January 1, 1996, and February 28, 2007. MAIN OUTCOME MEASURES: Presence of ESz or periodic epileptiform discharges (PEDs). RESULTS: Electrographic seizures were recorded in 14 patients (33%), and PEDs were recorded in 17 patients (40%). Twenty patients (48%) had either PEDs or ESz. Of the 14 patients with ESz, only 5 (36%) had a clinical correlate. Periodic epileptiform discharges (odds ratio=13.4; P=.001) and viral cause (odds ratio=13.0; P=.02) were independently associated with ESz. Both ESz (odds ratio=5.9; P=.02) and PEDs (odds ratio=6.1; P=.01) were independently associated with poor outcome at discharge (severe disability, vegetative state, or death). CONCLUSIONS: In patients with central nervous system infections undergoing continuous electroencephalographic monitoring, ESz and/or PEDs were frequent, occurring in 48% of our cohort. More than half of the ESz had no clinical correlate. Both ESz and PEDs were independently associated with poor outcome. Additional studies are needed to determine whether prevention or treatment of these electrographic findings improves outcome.

Inversion of multiple intersecting high-resolution crosshole GPR profiles for hydrological characterization at the Boise Hydrogeophysical Research Site

The integration of geophysical data into the subsurface characterization problem has been shown in many cases to significantly improve hydrological knowledge by providing information at spatial scales and locations that is unattainable using conventional hydrological measurement techniques. In particular, crosshole ground-penetrating radar (GPR) tomography has shown much promise in hydrology because of its ability to provide highly detailed images of subsurface radar wave velocity, which is strongly linked to soil water content. Here, we develop and demonstrate a procedure for inverting together multiple crosshole GPR data sets in order to characterize the spatial distribution of radar wave velocity below the water table at the Boise Hydrogeophysical Research Site (BHRS) near Boise, Idaho, USA. Specifically, we jointly invert 31 intersecting crosshole GPR profiles to obtain a highly resolved and consistent radar velocity model along the various profile directions. The model is found to be strongly correlated with complementary neutron porosity-log data and is further corroborated by larger-scale structural information at the BHRS. This work is an important prerequisite to using crosshole GPR data together with existing hydrological measurements for improved groundwater flow and contaminant transport modeling.

Harvest site influences the growth properties of adipose derived stem cells.

The therapeutic potential of adult stem cells may become a relevant option in clinical care in the future. In hand and plastic surgery, cell therapy might be used to enhance nerve regeneration and help surgeons and clinicians to repair debilitating nerve injuries. Adipose-derived stem cells (ASCs) are found in abundant quantities and can be harvested with a low morbidity. In order to define the optimal fat harvest location and detect any potential differences in ASC proliferation properties, we compared biopsies from different anatomical sites (inguinal, flank, pericardiac, omentum, neck) in Sprague-Dawley rats. ASCs were expanded from each biopsy and a proliferation assay using different mitogenic factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) was performed. Our results show that when compared with the pericardiac region, cells isolated from the inguinal, flank, omental and neck regions grow significantly better in growth medium alone. bFGF significantly enhanced the growth rate of ASCs isolated from all regions except the omentum. PDGF had minimal effect on ASC proliferation rate but increases the growth of ASCs from the neck region. Analysis of all the data suggests that ASCs from the neck region may be the ideal stem cell sources for tissue engineering approaches for the regeneration of nervous tissue.

Molecular investigation of lymph nodes in patients with colon cancer: a new road to better staging

Objective: Small nodal tumor infiltrates are identified by applying multilevel sectioning and immunohistochemistry (IHC) in addition to H&E (hematoxylin and eosin) stains of resected lymph nodes. However, the use of multilevel sectioning and IHC is very time-consuming and costly. The current standard analysis of lymph nodes in colon cancer patients is based on one slide per lymph node stained by H&E. A new molecular diagnostic system called ''One tep Nucleic Acid Amplification'' (OSNA) was designed for a more accurate detection of lymph node metastases. The objective of the present investigation was to compare the performance ofOSNAto current standard histology (H&E). We hypothesize that OSNA provides a better staging than the routine use of one slide H&E per lymph node.Methods: From 22 colon cancer patients 307 frozen lymph nodes were used to compare OSNA with H&E. The lymph nodes were cut into halves. One half of the lymph node was analyzed by OSNA. The semi-automated OSNA uses amplification of reverse-transcribed cytokeratin19 (CK19) mRNA directly from the homogenate. The remaining tissue was dedicated to histology, with 5 levels of H&E and IHC staining (CK19).Results: On routine evaluation of oneH&Eslide 7 patients were nodal positive (macro-metastases). All these patients were recognized by OSNA analysis as being positive (sensitivity 100%). Two of the remaining 15 patients had lymph node micro-metastases and 9 isolated tumor cells. For the patients with micrometastases both H&E and OSNA were positive in 1 of the 2 patients. For patients with isolated tumor cells, H&E was positive in 1/9 cases whereas OSNA was positive in 3/9 patients (IHC as a reference). There was only one case to be described as IHC negative/OSNA positive. On the basis of single lymph nodes the sensitivity of OSNA and the 5 levels of H&E and IHC was 94・5%.Conclusion: OSNA is a novel molecular tool for the detection of lymph node metastases in colon cancer patients which provides better staging compared to the current standard evaluation of one slide H&E stain. Since the use of OSNA allows the analysis of the whole lymph node, sampling bias and undetected tumor deposits due to uninvestigated material will be overcome. OSNA improves staging in colon cancer patients and may replace the current standard of H&E staining in the future.

Characterization of HbpR binding by site-directed mutagenesis of its DNA-binding site and by deletion of the effector domain.

In the presence of 2-hydroxybiphenyl, the enhancer binding protein, HbpR, activates the sigma54-dependent P(hbpC) promoter and controls the initial steps of 2-hydroxybiphenyl degradation in Pseudomonas azelaica. In the activation process, an oligomeric HbpR complex of unknown subunit composition binds to an operator region containing two imperfect palindromic sequences. Here, the HbpR-DNA binding interactions were investigated by site-directed mutagenesis of the operator region and by DNA-binding assays using purified HbpR. Mutations that disrupted the twofold symmetry in the palindromes did not affect the binding affinity of HbpR, but various mutations along a 60 bp region, and also outside the direct palindromic sequences, decreased the binding affinity. Footprints of HbpR on mutant operator fragments showed that a partial loss of binding contacts occurs, suggesting that the binding of one HbpR 'protomer' in the oligomeric complex is impaired whilst leaving the other contacts intact. An HbpR variant, devoid of its N-terminal sensing A-domain, was unable to activate transcription from the hbpC promoter while maintaining protection of the operator DNA in footprints. Wild-type HbpR was unable to activate transcription from the hbpC promoter when delta A-HbpR was expressed in the same cell, suggesting the formation of (repressing) hetero-oligomers. This model implies that HbpR can self-associate on its operator DNA without effector recognition or ATP binding. Furthermore, our findings suggest that the N-terminal sensing domain of HbpR is needed to activate the central ATPase domain rather than to repress a constitutively active C domain, as is the case for the related regulatory protein XylR.

The effect of mountain bike suspensions on vibrations and off-road uphill performance.

AIM: This study evaluates the effect of front suspension (FS) and dual suspension (DS) mountain-bike on performance and vibrations during off-road uphill riding. METHODS: Thirteen male cyclists (27+/-5 years, 70+/-6 kg, VO(2max)59+/-6 mL.kg(-1).min(-1), mean+/-SD) performed, in a random sequence, at their lactate threshold, an off-road uphill course (1.69 km, 212 m elevation gain) with both type of bicycles. Variable measured: a) VO(2) consumption (K4b2 analyzer, Cosmed), b) power output (SRM) c) gain in altitude and d) 3-D accelerations under the saddle and at the wheel (Physilog, EPFL, Switzerland). Power spectral analy- sis (Fourier) was performed from the vertical acceleration data. RESULTS: Respectively for the FS and DS mountain bike: speed amounted to 7.5+/-0.7 km.h(-1) and 7.4+/-0.8 km.h(-1), (NS), energy expenditure 1.39+/-0.16 kW and 1.38+/-0.18, (NS), gross efficiency 0.161+/-0.013 and 0.159+/-0.013, (NS), peak frequency of vibration under the saddle 4.78+/-2.85 Hz and 2.27+/-0.2 Hz (P<0.01) and median-frequency of vertical displacements of the saddle 9.41+/-1.47 Hz and 5.78+/-2.27 Hz (P<0.01). CONCLUSION: Vibrations at the saddle level of the DS bike are of low frequencies whereas those of the FS bike are mostly of high frequencies. In the DS bike, the torque produced by the cyclist at the pedal level may generate low frequency vibrations. We conclude that the DS bike absorbs more high frequency vibrations, is more comfortable and performs as well as the FS bicycle.

A randomized trial of glutamine and antioxidants in critically ill patients.

BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83). CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).