Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents.

CONTEXT: Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children. OBJECTIVE: To examine the independent and combined associations between objectively measured time in moderate- to vigorous-intensity physical activity (MVPA) and sedentary time with cardiometabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from 14 studies between 1998 and 2009 comprising 20 871 children (aged 4-18 years) from the International Children's Accelerometry Database. Time spent in MVPA and sedentary time were measured using accelerometry after reanalyzing raw data. The independent associations between time in MVPA and sedentary time, with outcomes, were examined using meta-analysis. Participants were stratified by tertiles of MVPA and sedentary time. MAIN OUTCOME MEASURES: Waist circumference, systolic blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and insulin. RESULTS: Times (mean [SD] min/d) accumulated by children in MVPA and being sedentary were 30 (21) and 354 (96), respectively. Time in MVPA was significantly associated with all cardiometabolic outcomes independent of sex, age, monitor wear time, time spent sedentary, and waist circumference (when not the outcome). Sedentary time was not associated with any outcome independent of time in MVPA. In the combined analyses, higher levels of MVPA were associated with better cardiometabolic risk factors across tertiles of sedentary time. The differences in outcomes between higher and lower MVPA were greater with lower sedentary time. Mean differences in waist circumference between the bottom and top tertiles of MVPA were 5.6 cm (95% CI, 4.8-6.4 cm) for high sedentary time and 3.6 cm (95% CI, 2.8-4.3 cm) for low sedentary time. Mean differences in systolic blood pressure for high and low sedentary time were 0.7 mm Hg (95% CI, -0.07 to 1.6) and 2.5 mm Hg (95% CI, 1.7-3.3), and for high-density lipoprotein cholesterol, differences were -2.6 mg/dL (95% CI, -1.4 to -3.9) and -4.5 mg/dL (95% CI, -3.3 to -5.6), respectively. Geometric mean differences for insulin and triglycerides showed similar variation. Those in the top tertile of MVPA accumulated more than 35 minutes per day in this intensity level compared with fewer than 18 minutes per day for those in the bottom tertile. In prospective analyses (N = 6413 at 2.1 years' follow-up), MVPA and sedentary time were not associated with waist circumference at follow-up, but a higher waist circumference at baseline was associated with higher amounts of sedentary time at follow-up. CONCLUSION: Higher MVPA time by children and adolescents was associated with better cardiometabolic risk factors regardless of the amount of sedentary time.

Wear of two artificial tooth materials in vivo: a 12-month pilot study.

STATEMENT OF PROBLEM: Wear of methacrylate artificial teeth resulting in vertical loss is a problem for both dentists and patients. PURPOSE: The purpose of this study was to quantify wear of artificial teeth in vivo and to relate it to subject and tooth variables. MATERIAL AND METHODS: Twenty-eight subjects treated with complete dentures received 2 artificial tooth materials (polymethyl methacrylate (PMMA)/double-cross linked PMMA fillers; 35%/59% (SR Antaris DCL, SR Postaris DCL); experimental 48%/46%). At baseline and after 12 months, impressions of the dentures were poured with improved stone. After laser scanning, the casts were superimposed and matched. Maximal vertical loss (mm) and volumetric loss (mm(3)) were calculated for each tooth and log-transformed to reduce variability. Volumetric loss was related to the occlusally active surface area. Linear mixed models were used to study the influence of the factors jaw, tooth, and material on adjusted (residual) wear values (alpha=.05). RESULTS: Due to drop outs (n=5) and unmatchable casts (n=3), 69% of all teeth were analyzed. Volumetric loss had a strong linear relationship to surface area (P<.001); this was less pronounced for vertical loss (P=.004). The factor showing the highest influence was the subject. Wear was tooth dependent (increasing from incisors to molars). However, these differences diminished once the wear rates were adjusted for occlusal area, and only a few remained significant (anterior versus posterior maxillary teeth). Another influencing factor was the age of the subject. CONCLUSIONS: Clinical wear of artificial teeth is higher than previously measured or expected. The presented method of analyzing wear of artificial teeth using a laser-scanning device seemed suitable.

Human skin in vitro permeation of bentazon and isoproturon formulations with or without protective clothing suit.

Skin exposures to chemicals may lead, through percutaneous permeation, to a significant increase in systemic circulation. Skin is the primary route of entry during some occupational activities, especially in agriculture. To reduce skin exposures, the use of personal protective equipment (PPE) is recommended. PPE efficiency is characterized as the time until products permeate through material (lag time, Tlag). Both skin and PPE permeations are assessed using similar in vitro methods; the diffusion cell system. Flow-through diffusion cells were used in this study to assess the permeation of two herbicides, bentazon and isoproturon, as well as four related commercial formulations (Basagran(®), Basamais(®), Arelon(®) and Matara(®)). Permeation was measured through fresh excised human skin, protective clothing suits (suits) (Microchem(®) 3000, AgriSafe Pro(®), Proshield(®) and Microgard(®) 2000 Plus Green), and a combination of skin and suits. Both herbicides, tested by itself or as an active ingredient in formulations, permeated readily through human skin and tested suits (Tlag < 2 h). High permeation coefficients were obtained regardless of formulations or tested membranes, except for Microchem(®) 3000. Short Tlag, were observed even when skin was covered with suits, except for Microchem(®) 3000. Kp values tended to decrease when suits covered the skin (except when Arelon(®) was applied to skin covered with AgriSafe Pro and Microgard(®) 2000), suggesting that Tlag alone is insufficient in characterizing suits. To better estimate human skin permeations, in vitro experiments should not only use human skin but also consider the intended use of the suit, i.e., the active ingredient concentrations and type of formulations, which significantly affect skin permeation.

Complications of shoulder arthroplasty for osteoarthritis with posterior glenoid wear.

BACKGROUND: Anatomical total shoulder arthroplasty (TSA) for glenohumeral osteoarthritis (OA) and severe posterior glenoid wear may entail early postoperative complications (recurrence of posterior subluxation, glenoid loosening). To avoid these mechanical problems, reverse shoulder arthroplasty (RSA) has recently been proposed, mainly for its intrinsic stability. Our purpose was to present the results of TSA and RSA in glenohumeral OA with posterior glenoid wear of at least 20°. HYPOTHESIS: By virtue of its constrained design, RSA could prevent recurrence of posterior subluxation and limit the occurrence of mechanical complications. MATERIALS AND METHODS: A consecutive series of 23 patients (27 shoulders) were treated for glenohumeral OA with total shoulder prostheses: 19 TSAs and 8 RSAs. Mean age was 70years (range, 47-85years), mean retroversion angle 28° (20°-50°) and mean subluxation index 74% (57-89%). Constant Score, Subjective Shoulder Value (SSV), QuickDASH and Simple Shoulder Test (SST) were measured, and radiological examinations were performed at a mean follow-up of 52months (24-95months). RESULTS: TSA and RSA patients respectively displayed Constant Scores of 65 and 65, SSV of 79% and 74%, QuickDASH of 16 and 27, and SST of 88 and 78. Two patients underwent surgical revision of TSA because of glenoid loosening; 52% of TSA patients presented complete radiolucent lines and 11% recurrence of posterior subluxation. CONCLUSION: Complications are frequently observed after shoulder arthroplasty for OA with severe glenoid retroversion. RSA could be an alternative to TSA for selected patients, independently of rotator cuff status. Studies on RSA in this specific indication with longer follow-up are now needed. LEVEL OF EVIDENCE: Level IV; retrospective case series.

A new approach to accurate measurement of uniaxial joint angles based on a combination of accelerometers and gyroscopes.

A new method of measuring joint angle using a combination of accelerometers and gyroscopes is presented. The method proposes a minimal sensor configuration with one sensor module mounted on each segment. The model is based on estimating the acceleration of the joint center of rotation by placing a pair of virtual sensors on the adjacent segments at the center of rotation. In the proposed technique, joint angles are found without the need for integration, so absolute angles can be obtained which are free from any source of drift. The model considers anatomical aspects and is personalized for each subject prior to each measurement. The method was validated by measuring knee flexion-extension angles of eight subjects, walking at three different speeds, and comparing the results with a reference motion measurement system. The results are very close to those of the reference system presenting very small errors (rms = 1.3, mean = 0.2, SD = 1.1 deg) and excellent correlation coefficients (0.997). The algorithm is able to provide joint angles in real-time, and ready for use in gait analysis. Technically, the system is portable, easily mountable, and can be used for long term monitoring without hindrance to natural activities.

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) antagonizes the genotoxic effects of alkylating agents. MGMT promoter methylation is the key mechanism of MGMT gene silencing and predicts a favorable outcome in patients with glioblastoma who are exposed to alkylating agent chemotherapy. This biomarker is on the verge of entering clinical decision-making and is currently used to stratify or even select glioblastoma patients for clinical trials. In other subtypes of glioma, such as anaplastic gliomas, the relevance of MGMT promoter methylation might extend beyond the prediction of chemosensitivity, and could reflect a distinct molecular profile. Here, we review the most commonly used assays for evaluation of MGMT status, outline the prerequisites for standardized tests, and evaluate reasons for difficulties in reproducibility. We critically discuss the prognostic and predictive value of MGMT silencing, reviewing trials in which patients with different types of glioma were treated with various chemotherapy schedules, either up-front or at recurrence. Standardization of MGMT testing requires comparison of different technologies across laboratories and prospectively validated cut-off values for prognostic or predictive effects. Moreover, future clinical trials will need to determine, for each subtype of glioma, the degree to which MGMT promoter methylation is predictive or prognostic, and whether testing should become routine clinical practice.

Toxic effects of brake wear particles on epithelial lung cells in vitro

Background: Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. Results: An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours ("full stop" and "normal deceleration"). The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity), by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p < 0.05) with increasing concentrations of metals on the particles (iron, copper and manganese, which were all strongly correlated with each other). Occludin was also negatively correlated with the intensity of reactive oxidative species. The concentrations of interleukin-8 were significantly correlated with increasing organic carbon concentrations. No correlation was observed between occludin and interleukin-8, nor between reactive oxidative species and interleukin-8. Conclusion: These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress. [Authors]

Patient- and therapy-related factors on the wear of denture teeth : results of a clinical trial

OBJECTIVE: When we examined a previously published prospective multi-center clinical trial in which complete denture-wearers were followed over a period of 2 years, we found that about 30% of the variability in the clinical wear data of denture teeth was due to unknown characteristics of the subjects. In the second part of the study, we try to identify which patient- and therapy-related factors may explain some of this variability. METHODS: The clinical wear data of denture teeth at different recall times (6, 12, 18, 24 months) in 89 subjects (at baseline) were correlated with the following parameters, which may all have an influence on the wear of denture teeth: age, gender, bruxism as reported by the subjects, number of prostheses used so far, time since last extraction, smoking, fit of dentures as judged by the subject and the clinician, average denture wearing time and wearing of denture during the night. To evaluate the influence of the different patient- and therapy-related variables, both a univariate analysis (one extra factor to the model) and a multivariate analysis were carried out using linear mixed models with the variable Log mean as the outcome. RESULTS: None of the patient- and therapy-related parameters showed a statistically significant effect on the wear of denture teeth. There was, however, a trend for women to show less wear compared to men and a trend of decreasing wear with increasing age. SIGNIFICANCE: Further research is required to identify the factors which are responsible for the high variability observed between the subjects regarding clinical wear data.

Whole-cell living biosensors--are they ready for environmental application?

Since the development of the first whole-cell living biosensor or bioreporter about 15 years ago, construction and testing of new genetically modified microorganisms for environmental sensing and reporting has proceeded at an ever increasing rate. One and a half decades appear as a reasonable time span for a new technology to reach the maturity needed for application and commercial success. It seems, however, that the research into cellular biosensors is still mostly in a proof-of-principle or demonstration phase and not close to extensive or commercial use outside of academia. In this review, we consider the motivations for bioreporter developments and discuss the suitability of extant bioreporters for the proposed applications to stimulate complementary research and to help researchers to develop realistic objectives. This includes the identification of some popular misconceptions about the qualities and shortcomings of bioreporters.

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]

Polyethylene wear in anatomic and reversed shoulder prostheses

Purpose: Polyethylene wear is a recurrent problem in joint arthroplasty. Small debris particles are also associated to inflammation reaction of the surrounding bone, eventually leading to the failure of the bound between the implant and the host bone, and implant loosening. The goal of this study was thus to estimate the volume of polyethylene wear of a reversed prosthesis, and compare it to an anatomic prosthesis, during one year of activities of daily living. Material and Methods: A numerical musculoskeletal model of the glenohumeral joint was used for this comparative study. The reversed (RP) and anatomic (AP) Aequalis prostheses were positioned in the numerical model. Eight levels of abduction were considered. Their daily frequency was estimated from in-vivo recorded data on healthy volunteers during activities of daily living. One year of use was simulated to predict the linear and volumetric wear. The volumetric wear was the difference of volume between the original and worn component. Results: With the AP, the contact pattern on the glenoid surface moved rapidly from the inferior to the superior side during the first 30 degrees of abduction, and then went back to the inferior side. With the RP, the contact pattern on the humeral cup surface remained at the inferior side. Contact pressure was 20 times lower with the RP than with the AP. One year of use produced a maximum linear wear of 0.2 mm with the AP, and 0.13 mm with the RP. However, the volumetric wear was 8.4 mm3 with the AP, but reached 44.6 mm3 with the RP. Conclusion: Polyethylene particles are a matter of concern with AP. Infiltration of these particles within the bone-implant interface can induce a implant loosening. This problem should not be underestimated with RP. It might be associated to a higher level of humeral stem loosening reported with RP. The long term survival of RP might be improved by using a highly cross-linked polyethylene, which has a better abrasion resistance but lower plastic resistance.

Assistance au suicide en hôpital de soins aigus: sommes-nous prêts [Physician-assisted suicide in university hospital: are we ready?]

Assisting people to commit suicide has generated a passionate public debate. In exceptional situations, access to this support can be granted to the demanders in a hospital environment. So did the CHUV and the academic hospitals of Geneva draw up a procedure permitting, in principle, the access to an assistance to commit suicide. Two recent clinical situations experienced in the CHUV's Service of internal medicine have created a lot of discussions, doubts and revealed, sometimes, divergent positions. By the light of this clinical cases, we wished to share the perspective of the internist in charge of the ethician, of the chaplain, of the medical director, of the psychiatrist and of the palliative care responsible. Theses complex situations illustrate the deep ambivalence felt by the clinicians confronted to situations which require a multidisciplinary approach.

Wear of two denture teeth materials in vivo-2-year results.

OBJECTIVE: (1) To quantify wear of two different denture tooth materials in vivo with two study designs, (2) to relate tooth variables to vertical loss. METHODS: Two different denture tooth materials had been used (experimental material=test; DCL=control). In study 1 (split-mouth, 6 test centers) 60 subjects received complete dentures, in study 2 (two-arm, 1 test center) 29 subjects. In study 1 the mandibular dentures were supported by implants in 33% of the subjects, in study 2 only in 3% of the subjects. Impressions of the dentures were taken and poured with improved stone at baseline and after 6, 12, 18 and 24 months. Each operator evaluated the wear subjectively. Wear analysis was carried out with a laser scanning device. Maximal vertical loss of the attrition zones was calculated for each tooth cusp and tooth. A mixed linear model was used to statistically analyse the logarithmically transformed wear data. RESULTS: Due to drop-outs and unmatchable casts, only 47 subjects of study 1 and 14 of study 2 completed the 2-year recall. Overall, 75% of all teeth present could be analysed. There was no statistically difference in the overall wear between the test and control material for either study 1 or study 2. The relative increase in wear over time was similar in both study designs. However, a strong subject effect and center effect were observed. The fixed factors included in the model (time, tooth, center, etc.) accounted for 43% of the variability, whereas the random subject effect accounted for another 30% of the variability, leaving about 28% of unexplained variability. More wear was consistently recorded in the maxillary teeth compared to the mandibular teeth and in the first molar teeth compared to the premolar teeth and the second molars. Likewise, the supporting cusps showed more wear than the non-supporting cusps. The amount of wear did not depend on whether or not the lower dentures were supported by implants. The subjective wear was correct in about 67% of the cases if it is postulated that a wear difference of 100μm should be subjectively detectable. SIGNIFICANCE: The clinical wear of denture teeth is highly variable with a strong patient effect. More wear can be expected in maxillary denture teeth compared to mandibular teeth, first molars compared to premolars and supported cusps compared to non-supported cusps. Laboratory data on the wear of denture tooth materials may not be confirmed in well-structured clinical trials probably due to the large inter-individual variability.

Physico-chemical characterization and oxidative reactivity evaluation of aged brake wear particles

Brake wear dust is a significant component of traffic emissions and has been linked to adverse health effects. Previous research found a strong oxidative stress response in cells exposed to freshly generated brake wear dust. We characterized aged dust collected from passenger vehicles, using microscopy and elemental analyses. Reactive oxygen species (ROS) generation was measured with acellular and cellular assays using 2′7-dichlorodihydrofluorescein dye. Microscopy analyses revealed samples to be heterogeneous particle mixtures with few nanoparticles detected. Several metals, primarily iron and copper, were identified. High oxygen concentrations suggested that the elements were oxidized. ROS were detected in the cell-free fluorescent test, while exposed cells were not dramatically activated by the concentrations used. The fact that aged brake wear samples have lower oxidative stress potential than fresh ones may relate to the highly oxidized or aged state of these particles, as well as their larger size and smaller reactive surface area.

Research and development, where people are exposed to nanomaterials

OBJECTIVES: Many nanomaterials (materials with structures smaller than 100 nm) have chemical, physical and bioactive characteristics of interest for novel applications. Considerable research efforts have been launched in this field. This study aimed to study exposure scenarios commonly encountered in research settings. METHODS: We studied one of the leading Swiss universities and first identified all research units dealing with nanomaterials. After a preliminary evaluation of quantities and process types used, a detailed analysis was conducted in units where more than a few micrograms were used per week. RESULTS: In the investigated laboratories, background levels were usually low and in the range of a few thousand particles per cubic centimeter. Powder applications resulted in concentrations of 10,000 to 100,000 particles/cm(3) when measured inside fume hoods, but there were no or mostly minimal increases in the breathing zone of researchers. Mostly low exposures were observed for activities involving liquid applications. However, centrifugation and lyophilization of nanoparticle-containing solutions resulted in high particle number levels (up to 300,000 particles/cm(3)) in work spaces where researchers did not always wear respiratory protection. No significant increases were found for processes involving nanoparticles bound to surfaces, nor were they found in laboratories that were visualizing properties and structure of small amounts of nanomaterials. CONCLUSIONS: Research activities in modern laboratories equipped with control techniques were associated with minimal releases of nanomaterials into the working space. However, the focus should not only be on processes involving nanopowders but should also be on processes involving nanoparticle-containing liquids, especially if the work involves physical agitation, aerosolization or drying of the liquids.