Concepts and determination of reference values for human biomonitoring of environmental contaminants

Human biomonitoring (HBM) of environmental contaminants plays an important role in estimating exposure and evaluating risk, and thus it has been increasingly applied in the environmental field. The results of HBM must be compared with reference values ( RV). The term ""reference values"" has always been related to the interpretation of clinical laboratory tests. For physicians, RV indicate ""normal values"" or ""limits of normal""; in turn, toxicologists prefer the terms ""background values"" or ""baseline values"" to refer to the presence of contaminants in biological fluids. This discrepancy leads to the discussion concerning which should be the population selected to determine RV. Whereas clinical chemistry employs an altered health state as the main exclusion criterion to select a reference population ( that is, a ""healthy"" population would be selected), in environmental toxicology the exclusion criterion is the abnormal exposure to xenobiotics. Therefore, the choice of population to determine RV is based on the very purpose of the RV to be determined. The present paper discusses the concepts and methodology used to determine RV for biomarkers of chemical environmental contaminants.

Postural Control in Elderly Persons with Osteoporosis: Efficacy of an Intervention Program to Improve Balance and Muscle Strength A Randomized Controlled Trial

Burke TN, Franc, a FJR, de Meneses SRF, Cardoso VI, Marques AP: Postural control in elderly persons with osteoporosis: Efficacy of an intervention program to improve balance and muscle strength: A randomized controlled trial. Am J Phys Med Rehabil 2010; 89: 549-556. Objective: To assess the efficacy of an exercise program aiming to improve balance and muscular strength, for postural control and muscular strength of women with osteoporosis. Design: Sample consisted of 33 women with osteoporosis, randomized into one of two groups: intervention group, in which exercises for balance and improvement of muscular strength of the inferior members were performed for 8 wks (n = 17, age 72.8 +/- 3.6 yrs); control group, which was women not practicing exercises (n = 16, age 74.4 +/- 3.7 yrs). At baseline and after 8 wks of treatment, postural control was assessed using a force plate (Balance Master, Neurocom), and muscular strength during ankle dorsiflexion, knee extension, and flexion was assessed by dynamometry. Results: Adherence to the program was 82%. When compared with the control group, individuals in the intervention group significantly improved the center of pressure velocity (P = 0.02) in the modified clinical test of sensory interaction for balance test, center of pressure velocity (P < 0.01), and directional control (P < 0.01) in limits of stability test, isometric force during ankle dorsiflexion (P = 0.01), knee extension (P < 0.01), and knee flexion (P < 0.01). Conclusions: Balance and strength exercises are effective in improving postural control and lower-limb strength in elderly women with osteoporosis.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.

Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis, in patients with severe aortic valve disease: Correlation with quantitative histopathology

Background Chronic aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). However, assessment of MF accumulation has only been possible through histologic analyses of endomyocardial biopsies. We sought to evaluate contrast-enhanced magnetic resonance imaging (ce-MRI) as a noninvasive method to identify the presence of increased MF in patients with severe AVD. Methods Seventy patients scheduled to undergo aortic valve replacement surgery were examined by cine and ce-MRI in a 1.5-T scanner. Cine images were used for the assessment of left ventricular (LV) volumes, mass, and function. Delayed-enhancement images were used to characterize the regions of MF. In addition, histologic analyses of myocardial samples obtained during aortic valve replacement surgery were used for direct quantification of interstitial MF. Ten additional subjects who died of noncardiac causes served as controls for the quantitative histologic analyses. Results Interstitial MF determined by histopathologic analysis was higher in patients with AVID than in controls (2.7% +/- 2.0% vs 0.6% +/- 0.2%, P =.001). When compared with histopathologic results, ce-MRI demonstrated a sensitivity of 74%, a specificity of 81%, and an accuracy of 76% to identify AVD patients with increased interstitial MF There was a significant inverse correlation between interstitial MF and LV ejection fraction (r = -0.67, P <.0001). Accordingly, patients with identifiable focal regions of MF by ce-MRI exhibited worse LV systolic function than those without MF (45% +/- 14% vs 65% +/- 14%, P <.0001). Conclusions Contrast-enhanced MRI allows for the noninvasive detection of focal regions of MF in patients with severe AVD. Moreover, patients with identifiable MF by ce-MRI exhibited worse LV functional parameters. (Am Heart J 2009; 157:361-8.)

Cytotoxic effects of crotamine are mediated through lysosomal membrane permeabilization

Crotamine, one of the main toxic components of Crotalus durissus terrificus venom, is a small non-enzymatic basic polypeptide, which causes hind limb paralysis and necrosis of muscle cells. it is well-known that several toxins penetrate into the cytosol through endocytosis, although in many cases the mechanism by which this occurs has not been fully investigated. Recently, using low concentrations of crotamine, we demonstrated the uptake of this toxin into actively proliferative cells via endocytosis, an event that ensues crotamine binding to cell membrane heparan sulfate proteoglycans. Thus, crotamine can be regarded as a cell-penetrating peptide that, additionally, has been shown to be able of delivering some biologically active molecules into various cells. Herein, we investigate one of the mechanisms by which crotamine exerts its cytotoxic effects by following its uptake into highly proliferative cells, as CHO-K1 cells. Crotamine accumulation in the acidic endosomal/lysosomal vesicles was observed within 5 min after treatment of these cells with a cytotoxic concentration of this toxin, a value determined here by classical MTT assay. This accumulation caused disruption of lysosomal vesicles accompanied by the leakage of these vesicles contents into the cytosol. This lysosomal lysis also promoted the release of cysteine cathepsin and an increase of caspase activity in the cytoplasm. This chain of events seems to trigger a cell death process. Overall, our data suggest that lysosomes are the primary targets for crotamine cytotoxicity, a proposal corroborated by the correlation between both the kinetics and concentration-dependence of crotamine accumulation in lysosome compartments and the cytotoxic effects of this protein in CHO-K1 cells. Although crotamine is usually regarded as a myotoxin, we observed that intraperitoneal injection of fluorescently labeled crotamine in living mice led to significant and rapid accumulation of this toxin in the cell cytoplasm of several tissues, suggesting that crotamine cytotoxicity might not be restricted to muscle cells. (C) 2008 Elsevier Ltd. All rights reserved.

PREDICTION OF FAT-FREE MASS BY BIOELECTRICAL IMPEDANCE ANALYSIS IN OLDER ADULTS FROM DEVELOPING COUNTRIES: A CROSS-VALIDATION STUDY USING THE DEUTERIUM DILUTION METHOD

Objective: Several limitations of published bioelectrical impedance analysis (BIA) equations have been reported. The aims were to develop in a multiethnic, elderly population a new prediction equation and cross-validate it along with some published BIA equations for estimating fat-free mass using deuterium oxide dilution as the reference method. Design and setting: Cross-sectional study of elderly from five developing countries. Methods: Total body water (TBW) measured by deuterium dilution was used to determine fat-free mass (FFM) in 383 subjects. Anthropometric and BIA variables were also measured. Only 377 subjects were included for the analysis, randomly divided into development and cross-validation groups after stratified by gender. Stepwise model selection was used to generate the model and Bland Altman analysis was used to test agreement. Results: FFM = 2.95 - 3.89 (Gender) + 0.514 (Ht(2)/Z) + 0.090 (Waist) + 0.156 (Body weight). The model fit parameters were an R(2), total F-Ratio, and the SEE of 0.88, 314.3, and 3.3, respectively. None of the published BIA equations met the criteria for agreement. The new BIA equation underestimated FFM by just 0.3 kg in the cross-validation sample. The mean of the difference between FFM by TBW and the new BIA equation were not significantly different; 95% of the differences were between the limits of agreement of -6.3 to 6.9 kg of FFM. There was no significant association between the mean of the differences and their averages (r = 0.008 and p = 0.2). Conclusions: This new BIA equation offers a valid option compared with some of the current published BIA equations to estimate FFM in elderly subjects from five developing countries.

A standardized measurement technique may improve the reliability of measurements of endometrial thickness and volume

Objective To investigate whether standardization of the multiplanar view (SMV) when evaluating the uterus using three-dimensional ultrasonography (3D-US) improves intra-and interobserver reliability and agreement with regard to endometrial measurement. Methods Two-dimensional (2D) and 3D-US was used to measure endometrial thickness by two observers in 30 women undergoing assisted reproduction treatment. Endometrial volume was measured with Virtual Organ Computer-aided AnaLysis (VOCAL (TM)) in the longitudinal (A) and coronal (C) planes using an unmodified multiplanar view (UMV) and a standardized multiplanar view (SMV). Measurement reliability was evaluated by intraclass correlation coefficient (ICC) and agreement was examined using Bland-Altman plots with limits of agreement (LoA). The ease of outlining the endometrial-myometrial interface was compared between the A-and C-planes using subjective assessment. Results Endometrial volume measurements using the SMV and A-plane were more reliable (intra-and interobserver ICCs, 0.979 and 0.975, respectively) than were measurements of endometrial thickness using 2D-US (intra-and interobserver ICCs, 0.742 and 0.702, respectively) or 3D-US (intra-and interobserver ICCs, 0.890 and 0.784, respectively). The LoAs were narrower for SMV than for UMV. Reliability and agreement were not much different between the A- and C-planes. However the observers agreed that delineating the endometrial-myometrial interface using the A-plane was easier (first and second observer, 50.0 and 46.7%, respectively) or `comparable` (50 and 53.3%, respectively), but never more difficult than using the C-plane. Conclusions Endometrial volume measurements are more reliable than endometrial thickness measurements and are best performed using SMV and the A-plane. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal volume and crown-rump length from 7 to 10 weeks of gestational age in singletons and twins

Objective(s): We intend to verify if fetal volume and crown-rump length were different between singletons and twins in pregnancies aged from 7 to 10 weeks and to evaluate if fetal volume is more accurate to determine the gestational age than crown-rump length at this gestational age. Study design: From 52 days (7 weeks and 3 days) to 73 days (10 weeks and 3 days) weekly three-dimensional Ultrasonography was per-formed in 20 twin fetuses and 20 singletons. Crown-rump length and fetal volume using VOCAL were assessed in all examinations. The `true` gestational age was based on oocyte retrieval. Results: At the age of 52 days, the crown-rump length was 11.74 +/- 0.27 mm (mean +/- S.D.) and 11.48 +/- 0.22 mm (singletons and twins, respectively), while the fetal volume was 0.354 +/- 0.015 cm(3) and 0.324 +/- 0.012 cm(3). At the gestational age of 73 days, the crown-rump length was 36.19 +/- 0.90 mm and 35.87 +/- 0.54 mm and the fetal volume was 6.204 +/- 0.090 cm(3) and 6.083 +/- 0.081 cm(3). The total relative increase observed was much higher for fetal volume than for CRL: 1705 +/- 301% vs. 210 +/- 33% in singletons and 1827 +/- 305% vs. 214 +/- 25% in twins. The 95% limits of agreement (+/- 2.3 days vs. +/- 3.2 days, fetal volume vs. crown-rump length) and the intraclass correlation coefficients (0.989 vs. 0.978) between the ""true"" gestational age and that predicted by fetal volume were better than those predicted by crown-rump length. No significant difference was identified between singletons and twins for both fetal volume and crown-rump length. Conclusion(s): Twins and singletons had similar fetal volume and crown-rump length between the 7th and 10th week of gestational age. Additionally, fetal volume assessed by VOCAL was better than crown-rump length to estimate the gestational age at the evaluated period. However, the improvement was small and probably without clinical significance. Condensation: Fetal volume and crown-rump length were similar between singletons and twins. Fetal volume relative increase was higher and the predicted gestational age was better. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Study of the psychometric qualities of the Brief Social Phobia Scale (BSPS) in Brazilian university students

Purpose: To perform a psychometric analysis of the Brazilian version of the Brief Social Phobia Scale (BSPS). Materials and methods: Hundred and seventy-eight university students of both genders aged on average 21.2 years and identified as Social Anxiety Disorder (SAD) cases and non-cases was studied, with the structured clinical interview for DSM-IV being used as a parameter. The different instruments were applied in an individual manner in the presence of a rater and of an observer. Results: The BSPS showed adequate internal consistency (0.48-0.88) and concurrent and divergent validity with the Beck Anxiety Inventory (BAI) (0.21-0.62), Social Phobia Inventory (0.24-0.82) and Self Statements During Public Speaking Scale (SSPS) (0.23-0.31). Discriminative validity revealed a sensitivity of 0.88-0.90 and a specificity of 0.81(0.83 for cut-off notes of 18/19. Factorial analysis demonstrated the presence of six factors that jointly explained 71.79% of data variance. Construct validity indicated some limits of the scale regarding the diagnosis of SAD. Inter-rater reliability was strong (0.86-1.00, p < 0.001). Conclusions: The BSPS is adequate for use with university students, although further studies in different cultures, samples and contexts are still necessary. (C) 2009 Elsevier Masson SAS. All rights reserved.

Protocol of orofacial myofunctional evaluation with scores

Objective: In the literature there is no validated instrument for the clinical evaluation of the orofacial myofunctional condition of children that will permit the examiner to express numerically his perception of the characteristics and behaviors observed. The proposal of this study is to describe a protocol for the evaluation of children aged 6-12 years in order to establish relations between the orofacial. myofunctional conditions and numerical scales. The protocol validity, reliability of the examiners and agreement between them was analyzed. Methods: Eighty children aged 6-12 years participated in the study. All were evaluated and 30 were selected at random for the analyses (age range: 72-149 months, mean = 103.3, S.D. = 23.57). Individuals with and without orofacial myofunctional. disorders were included. The examiners were two speech therapists property calibrated in orofacial myofunctional evaluation. Two protocols were constructed. One, based on traditional models, was called traditional orofacial. myofunctional. evaluation (TOME), and the other, with the addition of numerical scales, was called orofacial myofunctional. evaluation with scores (OMES). The clinical conditions included were: appearance, posture and mobility of lips, tongue, cheeks and jaws, respiration, mastication and deglutition. Statistical analysis was performed using the split-half reliability method. Means, standard deviations and the Spearman correlation coefficient were also calculated. Results: There was a statistically significant correlation between the evaluations of 30 children assessed with the TOME and OMES protocols (r = 0.85, p < 0.01). The reliability between protocols was 0.92. The test-retest reliability of the OMES instrument was 0.99 and the correlation was 0.98. Reliability between examiners 1 and 2 using the OMES protocol was 0.99, and the correlation was 0.98 (P < 0.01). Conclusion: The OMES protocot proved to be a valid and reliable instrument for orofacial myofunctional evaluation, permitting the grading of orofacial myofunctional conditions within the limits of the selected items. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

LC-MS/MS quantitation of plasma progesterone in cattle

Quantitation of progesterone (P(4)) in biological fluids is often performed by radioimmunoassay (RIA), whereas liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been used much less often. Due to its autoconfirmatory nature, LC-MS/MS greatly minimizes false positives and interference. Herein we report and compare with RIA an optimized LC-MS/MS method for rapid, efficient, and cost-effective quantitation of P(4) in plasma of cattle with no sample derivatization. The quantitation of plasma P(4) released from three nonbiodegradable, commercial, intravaginal P(4)-releasing devices (IPRD) over 192 h in six ovariectomized cows was compared in a pairwise study as a test case. Both techniques showed similar P(4) kinetics (P > 0.05) whereas results of P(4) quantitation by RIA were consistently higher compared with LC-MS/MS (P < 0.05) due to interference and matrix effects. The LC-MS/MS method was validated according to the recommended analytical standards and displayed P(4) limits of detection (LOD) and quantitation (LOQ) of 0.08 and a 0.25 ng/mL, respectively. The high selective LC-MS/MS method proposed herein for P(4) quantitation eliminates the risks associated with radioactive handling; it also requires no sample derivatization, which is a common requirement for LC-MS/MS quantitation of steroid hormones. Its application to multisteroid assays is also viable, and it is envisaged that it may provide a gold standard technique for hormone quantitation in animal reproductive science studies. (C) 2011 Elsevier Inc. All rights reserved.

Human settlements: Australia state of the environment report, 2001

Australia’s transition to the 21st century has been marked by an extended period of economic prosperity unmatched for several decades, but one in which a series of question marks are being raised in three principal areas: in relation to the environment, the social well-being of the population, and the future path of economic development. The first concern, which is of primary interest in this report, relates to the physical environment of cities and their surrounding regions, and the range of pressures exerted by population and human activity. The report begins by noting the increasing divergence of the prime indicator of national economic performance—gross domestic product (GDP)—from the Genuine Progress Indicator (GPI). GPI is a new experimental measure of sustainable development that accommodates factors currently unaccounted for in GDP, such as income distribution, value of household work, cost of unemployment, and various other social and environmental costs. The divergence of these two indicators in recent decades suggests that Australia’s growth has been heavily dependent on the draw-down of the nation’s stocks of capital assets (its infrastructure), its human and social capital, and its natural capital (Hamilton 1997).

The Importance of Adhesive Area Delimitation in a Microshear Bond Strength Experimental Design

Purpose: The purpose of this study was to assess the influence of adhesive area delimitation on the microshear bond strength of different adhesives to dentin. Materials and Methods: Eighteen bovine incisors were sectioned and the exposed dentin surfaces were prepared with 600-grit SIC paper. These teeth were randomly divided into three groups, according to the adhesive to be applied: two-step etch-and-rinse Adper Single Bond 2 (3M ESPE), two-step self-etching Clearfil SE Bond (Kuraray), and one-step Clearfil S(3) Bond (Kuraray). On each dentin surface, 4 samples were built up with the composite resin Z100 (3M ESPE); on 2 of these, a suggested area delimitation technique was employed. After 24 h of storage in water at 37 degrees C, samples were subjected to the microshear bond strength test, and the failure modes were evaluated under optical and scanning electron microscopes. The obtained results were statistical analyzed using two-way ANOVA and Tukey`s test. Results: Groups without area delimitation presented significantly higher bond strength results (p < 0.05) and a higher incidence of cohesive failures. In these groups, fractures tended to occur beyond the limits of the actual adhesive area, while the area restriction technique succeeded in avoiding this phenomenon. The three adhesives performed similarly when area delimitation was employed (p > 0.05), but Clearfil S(3) Bond showed significantly higher bond strength results when no area delimitation was taken into account (p < 0.05). Conclusion: The extension of the adhesive area beyond the limits of the composite cylinder may play an important role in the results of microshear bond strength tests, while the suggested area delimitation technique may lead to less questionable outcomes.

Diffusion modeling of percutaneous absorption kinetics: 2. Finite vehicle volume and solvent deposited solids

The diffusion model for percutaneous absorption is developed for the specific case of delivery to the skin being limited by the application of a finite amount of solute. Two cases are considered; in the first, there is an application of a finite donor (vehicle) volume, and in the second, there are solvent-deposited solids and a thin vehicle with a high partition coefficient. In both cases, the potential effect of an interfacial resistance at the stratum corneum surface is also considered. As in the previous paper, which was concerned with the application of a constant donor concentration, clearance limitations due to the viable eqidermis, the in vitro sampling rate, or perfusion rate in vivo are included. Numerical inversion of the Laplace domain solutions was used for simulations of solute flux and cumulative amount absorbed and to model specific examples of percutaneous absorption of solvent-deposited solids. It was concluded that numerical inversions of the Laplace domain solutions for a diffusion model of the percutaneous absorption, using standard scientific software (such as SCIENTIST, MicroMath Scientific software) on modern personal computers, is a practical alternative to computation of infinite series solutions. Limits of the Laplace domain solutions were used to define the moments of the flux-time profiles for finite donor volumes and the slope of the terminal log flux-time profile. The mean transit time could be related to the diffusion time through stratum corneum, viable epidermal, and donor diffusion layer resistances and clearance from the receptor phase. Approximate expressions for the time to reach maximum flux (peak time) and maximum flux were also derived. The model was then validated using reported amount-time and flux-time profiles for finite doses applied to the skin. It was concluded that for very small donor phase volume or for very large stratum corneum-vehicle partitioning coefficients (e.g., for solvent deposited solids), the flux and amount of solute absorbed are affected by receptor conditions to a lesser extent than is obvious for a constant donor constant donor concentrations. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:504-520, 2001.

Estimation of body water compartments in cirrhosis by multiple-frequency bioelectrical-impedance analysis

Estimation of total body water by measuring bioelectrical impedance at a fixed frequency of 50 kHz is useful in assessing body composition in healthy populations. However, in cirrhosis, the distribution of total body water between the extracellular and intracellular compartments is of greater clinical importance. We report an evaluation of a new multiple-frequency bioelectrical-impedance analysis technique (MFBIA) that may quantify the distribution of total body water in cirrhosis. In 21 cirrhotic patients and 21 healthy control subjects, impedance to the Row of current was measured at frequencies ranging from 4 to 1012 kHz. These measurements were used to estimate body water compartments and then compared with total body water and extracellular water determined by isotope methodology. In cirrhotic patients, extracellular water and total body water (as determined by isotope methods) were well predicted by MFBIA (r = 0.73 and 0.89, respectively).;However, the 95% confidence intervals of the limits of agreement between MFBIA and the isotope methods were +/- 14% and +/-9% for cirrhotics (extracellular water and total body water, respectively) and +/-9% and +/-9% for cirrhotics without ascites. The 95% confidence intervals estimated from the control group were +/-10% and +/-5% for extracellular water and total body water, respectively. Thus, despite strong correlations between MFBIA and isotope measurements, the relatively large limits of agreement with accepted techniques suggest that the MFBIA technique requires further refinement before it can be routinely used to determine the nutritional assessment of individual cirrhotic patients. Nutrition 2001,17.31-34. (C)Elsevier Science Inc. 2001.