Children's lead exposure in the U.S.: Application of a national-scale, probabilistic aggregate model with a focus on residential soil and dust lead (Pb) scenarios.

Lead (Pb) exposures from soil and dust ingestion contribute to children's blood lead levels (BLLs) in the United States. The U.S. Environmental Protection Agency (EPA)'s Strategy to Reduce Lead Exposures and Disparities in U.S. Communities and the Federal Action Plan to Reduce Childhood Lead Exposure describe multi-pronged collaborative approaches. These include reducing multi-media lead exposures nationally using analytical tools such as EPA's Stochastic Human Exposure and Dose Simulation model for lead [SHEDS-Pb; formerly known as SHEDS-IEUBK (Integrated Exposure Uptake Biokinetic model)], which was initially developed and applied with a focus on children's drinking water exposures. In this study we applied SHEDS-Pb to determine what residential soil Pb and dust Pb concentrations (individually and their sum) can keep BLLs of potentially exposed young children in the general U.S. population below specified values, considering aggregate exposures from water, soil, dust, food, and air. We considered two age groups (1 to <2 years and 2 to <6 years), two BLL values (5 µg/dL and 3.5 µg/dL), and two population percentiles (95th and 97.5th). Sensitivity analyses were conducted using several alternative model inputs and data sets, yielding 15 scenarios summarized in the paper. Of those scenarios, we focused on ones with the most recent science and available data. Modeled soil Pb concentrations by age group, population percentile and reference BLL scenarios for the focus scenarios ranged from 70 ppm to 220 ppm; and modeled dust Pb concentrations ranged from 110 ppm to 240 ppm. These results are consistent with current soil and dust Pb concentrations in the U.S. general population and are lower than most of the current U.S. Federal standards. Estimated BLLs compared well with measured BLLs from CDC's NHANES 2009-2016 (0-27 % relative error for focus scenarios). This analysis can be used to inform EPA and other federal Pb efforts.

Intraspecific variability in heat resistance of fungal conidia.

Microbial species are inherently variable, which is reflected in intraspecies genotypic and phenotypic differences. Strain-to-strain variation gives rise to variability in stress resistance and plays a crucial role in food safety and food quality. Here, strain variability in heat resistance of asexual spores (conidia) of the fungal species Aspergillus niger, Penicillium roqueforti and Paecilomyces variotii was quantified and compared to bacterial variability found in the literature. After heat treatment, a 5.4- to 8.6-fold difference in inactivation rate was found between individual strains within each species, while the strain variability of the three fungal species was not statistically different. We evaluated whether the degree of intraspecies variability is uniform, not only within the fungal kingdom, but also amongst different bacterial species. Comparison with three spore-forming bacteria and two non-spore-forming bacteria revealed that the variability of the different species was indeed in the same order of magnitude, which hints to a microbial signature of variation that exceeds kingdom boundaries.

Atrial fibrillation in chronic heart failure patients with reduced ejection fraction: The CHECK-HF registry.

BACKGROUND: Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy. METHODS: We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines. RESULTS: 2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07). CONCLUSION: In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF.

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

The Indoor Fungus Cladosporium halotolerans Survives Humidity Dynamics Markedly Better than Aspergillus niger and Penicillium rubens despite Less Growth at Lowered Steady-State Water Activity.

UNLABELLED: Indoor fungi cause damage in houses and are a potential threat to human health. Indoor fungal growth requires water, for which the terms water activity (aw) and relative humidity (RH) are used. The ability of the fungi Aspergillus niger, Cladosporium halotolerans, and Penicillium rubens at different developmental stages to survive changes in aw dynamics was studied. Fungi grown on media with high aw were transferred to a controlled environment with low RH and incubated for 1 week. Growth of all developmental stages was halted during incubation at RHs below 75%, while growth continued at 84% RH. Swollen conidia, germlings, and microcolonies of A. niger and P. rubens could not reinitiate growth when retransferred from an RH below 75% to a medium with high aw All developmental stages of C. halotolerans showed growth after retransfer from 75% RH. Dormant conidia survived retransfer to medium with high aw in all cases. In addition, retransfer from 84% RH to medium with high aw resulted in burst hyphal tips for Aspergillus and Penicillium Cell damage of hyphae of these fungi after incubation at 75% RH was already visible after 2 h, as observed by staining with the fluorescent dye TOTO-1. Thus, C. halotolerans is more resistant to aw dynamics than A. niger and P. rubens, despite its limited growth compared to that of these fungi at a lowered steady-state aw The survival strategy of this phylloplane fungus in response to the dynamics of aw is discussed in relation to its morphology as studied by cryo-scanning electron microscopy (cryo-SEM). IMPORTANCE: Indoor fungi cause structural and cosmetic damage in houses and are a potential threat to human health. Growth depends on water, which is available only at certain periods of the day (e.g., during cooking or showering). Knowing why fungi can or cannot survive indoors is important for finding novel ways of prevention. Until now, the ability of fungi to grow on media with little available water at steady state (unchanging conditions) has been important for evaluating whether a fungus can grow indoors. In the present study, we found that the fungus Cladosporium halotolerans, a common indoor fungus, is more resistant to changes in available water than the fungi Aspergillus niger and Penicillium rubens, despite the fact that the latter fungi can grow on media with low water availability. We concluded that the ability of fungi to deal with changes in humidity is at least as important as the ability to grow on low-water media.

Dental floss as a possible risk for the development of peri-implant disease: an observational study of 10 cases.

AIM: To report on a possible relationship between the use of dental floss or superfloss and the development of peri-implantitis. MATERIALS AND METHODS: Ten patients with progressive peri-implantitis with an intensive oral hygiene protocol, which consisted of extensive professional supra- and submucosal cleaning, and not responding to this therapy were scheduled for examination. Plaque and bleeding indices and probing depth measurements were assessed, and radiographic examination was performed every two years. RESULTS: In all ten cases, remnants of dental floss were found around the neck and coronal part of a dental implant. After careful removal of these floss remnants and implant cleansing, a significant improvement in the peri-implant conditions in nine of ten cases was noted. In one case, peri-implant probing depth decreased substantially. However, bleeding on probing was still present. In vitro testing yielded that the application of various types of dental floss on the exposed rough implant surfaces may easily lead to tearing of floss fibers. This may result in the deposition of floss remnants on rough implant surfaces, which, in turn, may lead to the development of plaque-related peri-implant inflammation and, subsequently, bone loss. CONCLUSION: In case of exposed rough surfaces of the dental implant, the peri-implant conditions may be jeopardized by the application of dental floss, and hence, the utilization of interproximal brushes or toothpicks may be preferred for daily home care practices.

Using the Lower Limit of Normal Instead of the Conventional Cutoff Values to Define Predictors of Pulmonary Function Impairment in Subjects With Chronic Heart Failure.

BACKGROUND: Using the newer lower limit of normal criterion instead of the conventional cutoff values to define pulmonary function abnormalities may result in different predictors of pulmonary function impairment in patients with heart failure. Therefore, we assessed predictors of pulmonary function impairment in subjects with chronic heart failure according to the lower limit of normal in comparison with conventional cutoff values. METHODS: In this prospective cross-sectional study, 164 chronic heart failure subjects (age 68 ± 10 y, 78% men, 88% New York Heart Association class I-II) with left ventricular ejection fraction <40% underwent pulmonary function tests. Predictors of pulmonary function impairment were assessed using the lower limit of normal and conventional cutoff values (ie, 80% predicted value and the fixed ratio of FEV1/FVC <0.7). RESULTS: The lower limit of normal criterion identified an extra independent predictor of diffusion impairment compared with the 80% predicted value; in addition to body mass index, pack-years, and alveolar volume, female sex also turned out to be an independent predictor. A smoking history of ≥10 pack-years was a significant predictor of diffusion impairment and airway obstruction using the lower limit of normal criterion but not using the conventional cutoff values. However, lowering the cutoff points of conventional criteria to match the more stringent lower limit of normal and thus avoid overdiagnosis of diffusion impairment and airway obstruction in the elderly produced similar results as the lower limit of normal. CONCLUSIONS: The lower limit of normal identifies more predictors of diffusion impairment and airway obstruction compared with conventional cutoff values in subjects with chronic heart failure with left ventricular systolic dysfunction. However, lowering the conventional cutoff points yielded similar results as the lower limit of normal. (ClinicalTrials.gov registration NCT01429376.).

Xerotolerant Cladosporium sphaerospermum Are Predominant on Indoor Surfaces Compared to Other Cladosporium Species.

Indoor fungi are a major cause of cosmetic and structural damage of buildings worldwide and prolonged exposure of these fungi poses a health risk. Aspergillus, Penicillium and Cladosporium species are the most predominant fungi in indoor environments. Cladosporium species predominate under ambient conditions. A total of 123 Cladosporium isolates originating from indoor air and indoor surfaces of archives, industrial factories, laboratories, and other buildings from four continents were identified by sequencing the internal transcribed spacer (ITS), and a part of the translation elongation factor 1α gene (TEF) and actin gene (ACT). Species from the Cladosporium sphaerospermum species complex were most predominant representing 44.7% of all isolates, while the Cladosporium cladosporioides and Cladosporium herbarum species complexes represented 33.3% and 22.0%, respectively. The contribution of the C. sphaerospermum species complex was 23.1% and 58.2% in the indoor air and isolates from indoor surfaces, respectively. Isolates from this species complex showed growth at lower water activity (≥ 0.82) when compared to species from the C. cladosporioides and C. herbarum species complexes (≥ 0.85). Together, these data indicate that xerotolerance provide the C. sphaerospermum species complex advantage in colonizing indoor surfaces. As a consequence, C. sphaerospermum are proposed to be the most predominant fungus at these locations under ambient conditions. Findings are discussed in relation to the specificity of allergy test, as the current species of Cladosporium used to develop these tests are not the predominant indoor species.

Separate effects of moisture content and water activity on the hyphal extension of Penicillium rubens on porous media.

To prevent indoor fungal growth, understanding the moisture relations of fungi is a key element. Indoor moisture is quantified by the relative humidity (RH). RH controls the water activity of the indoor materials that fungi grow on, a well-studied parameter known to limit fungal growth. RH, however, also controls the amount of water present in these materials, the moisture content. The significance of the moisture content of these materials to indoor fungal growth is currently overlooked. In the work reported here, growth experiments with the indoor fungus Penicillium rubens on gypsum substrates were performed to test whether the moisture content influences growth on porous materials. Second, we report the development of a video microscopy method that for the first time quantified hyphal growth on a porous material. It is found that a higher moisture content leads to earlier colonization and higher hyphal extension rates. This is a fundamental step in unravelling the effect of RH on indoor fungal growth. The real-time monitoring of colonization of gypsum provides a new view of growth on indoor surfaces.

10-year survival rate and the incidence of peri-implant disease of 374 titanium dental implants with a SLA surface: a prospective cohort study in 177 fully and partially edentulous patients.

PURPOSE: This prospective cohort study evaluates the 10-year survival and incidence of peri-implant disease at implant and patient level of sandblasted, large grid, and acid-etched titanium dental implants (Straumann, soft tissue level, SLA surface) in fully and partially edentulous patients. MATERIAL AND METHODS: Patients who had dental implant surgery in the period between November 1997 and June 2001, with a follow-up of at least 10 years, were investigated for clinical and radiological examination. Among the 506 inserted dental implants in 250 patients, 10-year data regarding the outcome of implants were available for 374 dental implants in 177 patients. In the current study, peri-implantitis was defined as advanced bone loss (≧1.5 mm. postloading) in combination with bleeding on probing. RESULTS: At 10-year follow-up, only one implant was lost (0.3%) 2 months after implant surgery due to insufficient osseointegration. The average bone loss at 10 year postloading was 0.52 mm. Advanced bone loss at 10-year follow-up was present in 35 dental implants (9.8%). Seven percent of the observed dental implants showed bleeding on probing in combination with advanced bone loss and 4.2% when setting the threshold for advanced bone loss at 2.0 mm. Advanced bone loss without bleeding on probing was present in 2.8% of all implants. CONCLUSION: In this prospective study, the 10-year survival rate at implant and patient level was 99.7% and 99.4%, respectively. Peri-implantitis was present in 7% of the observed dental implants according to the above-mentioned definition of peri-implantitis. This study shows that SLA implants offer predictable long-term results as support in the treatment of fully and partially edentulous patients.

Pulmonary function impairment in patients with chronic heart failure: lower limit of normal versus conventional cutoff values.

OBJECTIVE: To determine the prevalence of pulmonary function abnormalities in patients with chronic heart failure (HF) according to recent American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines using the lower limit of normal (LLN) compared to conventional cutoff values. BACKGROUND: Recent ATS/ERS guidelines recommend the use of the LLN instead of the conventional cutoff values to define pulmonary function impairment to avoid misclassification of patients. However, studies addressing the prevalence of pulmonary function abnormalities according to both definitions in patients with chronic HF are lacking. METHODS: In this prospective cross-sectional study, 164 chronic HF outpatients (age 68 ± 10 years, 78% men, 88% New York Heart Association class I-II) with left ventricular ejection fraction < 40% underwent spirometry and measurement of diffusing capacity. Body plethysmography was performed in patients with abnormal spirometry results. RESULTS: Diffusion impairment and airway obstruction were found in 44-58% and 26-37% of the patients, respectively, depending on the definition used (LLN versus conventional cutoff values, p < 0.05). However, restriction was infrequent, irrespective of the definition used (7% versus 5%, respectively, p > 0.05). The LLN identified fewer patients with abnormal lung function, whereas the conventional cutoff values classified more patients with diffusion impairment, airway obstruction, or a mixed category. Twenty-seven percent of patients were misclassified by the conventional cutoff values. CONCLUSION: Pulmonary function abnormalities, especially diffusion impairment and airway obstruction, were highly prevalent in patients with chronic HF. Conventional cutoff values classified more patients with diffusion impairment, airway obstruction, or a mixed category compared to the LLN.

Co-crystallization with nicotinamide in two conformations lowers energy but expands volume.

A dispersion-corrected density functional theory method has been used to study the formation energies and volumes of cocrystals. For four cocrystals of nicotinamide (NIC) and (R)-mandelic acid, a broad agreement is found between experimental and computed values. We report that cocrystals containing NIC are anomalous as their formation generally decreases energy but expands volume. In this respect, the formation of NIC cocrystals is in contrast to most physical processes, but similar to water freezing. As in the case of water freezing, the cocrystallization with NIC leads to stronger hydrogen bonds and looser molecular packing, a combination that is likely responsible for the anticorrelation between energy and volume. NIC has two conformers 4 kJ/mol apart in energy and both can form cocrystals, with the resulting structures having comparable formation energies and volumes. These results are relevant for understanding the nature of cocrystallization and why NIC is a prolific cocrystal former.

COPD in chronic heart failure: less common than previously thought?

BACKGROUND: Using a fixed ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 0.70 instead of the lower limit of normal (LLN) to define chronic obstructive pulmonary disease (COPD) may lead to overdiagnosis of COPD in elderly patients with heart failure (HF) and consequently unnecessary treatment with possible adverse health effects. OBJECTIVE: The aim of this study was to determine COPD prevalence in patients with chronic HF according to two definitions of airflow obstruction. METHODS: Spirometry was performed in 187 outpatients with stable chronic HF without pulmonary congestion who had a left ventricular ejection fraction <40% (mean age 69 ± 10 years, 78% men). COPD diagnosis was confirmed 3 months after standard treatment with tiotropium in newly diagnosed COPD patients. RESULTS: COPD prevalence varied substantially between 19.8% (LLN-COPD) and 32.1% (GOLD-COPD). Twenty-three of 60 patients (38.3%) with GOLD-COPD were potentially misclassified as having COPD (FEV1/FVC < 0.7 but > LLN). In contrast to patients with LLN-COPD, potentially misclassified patients did not differ significantly from those without COPD regarding respiratory symptoms and risk factors for COPD. CONCLUSIONS: One fifth, rather than one third, of the patients with chronic HF had concomitant COPD using the LLN instead of the fixed ratio. LLN may identify clinically more important COPD than a fixed ratio of 0.7.

Bronchodilator responsiveness in patients with chronic heart failure.

OBJECTIVE: The aim of this study was to evaluate the effect of inhaled bronchodilators on pulmonary function and dyspnea in patients with chronic heart failure (HF). BACKGROUND: Conflicting data exist on whether bronchodilators may improve pulmonary function and dyspnea in patients with chronic HF. METHODS: In this retrospective observational study we analyzed data of 116 chronic HF outpatients with systolic dysfunction who underwent spirometry and Borg dyspnea measurements before and after inhalation of 400 µg salbutamol and 80 µg ipratropium. Patients with chronic obstructive pulmonary disease (COPD) or asthma were excluded. RESULTS: Bronchodilators fully reversed airway obstruction (AO) in 25 of 64 (39.1%) patients with pre-bronchodilator AO. All spirometric measurements, except for forced vital and inspiratory capacities, improved significantly post-bronchodilation. Absolute and percent improvements in forced expiratory volume in 1 s (FEV1) were more pronounced in patients with persistent AO post-bronchodilation compared to those without AO (0.19 ± 0.18 L and 8.4 ± 7.3% versus 0.11 ± 0.12 L and 4.3 ± 4.0%, p < 0.05). Significant bronchodilator responsiveness of FEV1 (>200 mL and >12%) was noted in 12.1% and was more frequent in patients with persistent AO and fully reversible AO than in those without AO (23.1% and 16.0% versus 1.9%, p < 0.05). We measured a small, albeit significant improvement in dyspnea (0.7 ± 1.2 versus 0.9 ± 1.3, p = 0.002). CONCLUSIONS: Inhaled bronchodilators may have an additional role in the management of patients with chronic HF because of their potential to improve pulmonary function, especially in those with AO. The clinical usefulness and possible adverse events of bronchodilators need to be further established.

Manual vs. automated analysis of polysomnographic recordings in patients with chronic obstructive pulmonary disease.

PURPOSE: The sleep quality, as assessed by polysomnography (PSG), of patients with chronic obstructive pulmonary disease (COPD) can be severely disturbed. The manual analysis of PSGs is time-consuming, and computer systems have been developed to automatically analyze PSGs. Studies on the reliability of automated analyses in healthy subjects show varying results, and the purpose of this study was to assess whether automated analysis of PSG by one certain automatic system in patients with COPD provide accurate outcomes when compared to manual analysis. METHODS: In a retrospective study, the full-night polysomnographic recordings of patients with and without COPD were analyzed automatically by Matrix Sleep Analysis software and manually. The outcomes of manual and automated analyses in both groups were compared using Bland-Altman plots and Students' paired t tests. RESULTS: Fifty PSGs from patients with COPD and 57 PSGs from patients without COPD were included. In both study groups, agreement between manual and automated analysis was poor in nearly all sleep and respiratory parameters, like total sleep time, sleep efficiency, sleep latency, amount of rapid eye movement sleep and other sleep stages, number of arousals, apnea-hypopnea index, and desaturation index. CONCLUSION: Automated analysis of PSGs by the studied automated system in patients with COPD has poor agreement with manual analysis when looking at sleep and respiratory parameters and should, therefore, not replace the manual analysis of PSG recordings in patients with COPD.

Empirical van der Waals corrections to solid-state density functional theory: Iodine and phosphorous containing molecular crystals.

Parameters are derived for a molecular mechanics type dispersive correction to solid-state density functional theory calculations on molecular crystals containing iodine and phosphorous. The molecular C(6) coefficients are derived from photoabsorption differential oscillator strength spectra determined from accurate (e,e) dipole spectra. The cross-over parameters, which ensure correct behavior at short internuclear distances, are obtained by fitting predicted crystal lattice parameters to experimental data. The accuracy of the parameterization is assessed by optimizing the experimental structures of several additional phosphorous and iodine containing molecular crystals and by examining the relative stabilities of the known polymorphs of phosphorous pentoxide and the stabilities of different packings of an iodine containing molecular crystal, 2,9-bis(iodo)anthanthrone, which has been the subject of a crystal structure prediction study. Optimizations of the experimental crystal structures did not lead to significant geometric deviations. The optimized experimental structure of 2,9-bis(iodo)anthanthrone is the lowest energy packing found, indicating a satisfactory description of both energy and structure for these molecular crystals.

Prediction of the mechanical behaviour of crystalline solids.

PURPOSE: To explore the use of crystal inter-planar d-spacings and slip-plane interaction energies for predicting and characterising mechanical properties of crystalline solids. METHODS: Potential relationships were evaluated between mechanical properties and inter-planar d-spacing, inter-planar interaction energy, and dispersive surface energy as determined using inverse gas chromatography (IGC) for a set of pharmaceutical materials. Inter-planar interaction energies were determined by molecular modelling. RESULTS: General trends were observed between mechanical properties and the largest inter-planar d-spacing, inter-planar interaction energies, and IGC dispersive surface energy. A number of materials showed significant deviations from general trends. Weak correlations and outliers were rationalised. CONCLUSIONS: Results suggest that the highest d-spacing of a material could serve as a first-order indicator for ranking mechanical behaviour of pharmaceutical powders, but with some reservation. Inter-planar interaction energy normalised for surface area shows only a weak link with mechanical properties and does not appear to capture essential physics of deformation. A novel framework linking mechanical properties of crystals to the distinct quantities, slip-plane energy barrier and inter-planar interaction (detachment) energy is proposed.

Influence of solvent on the morphology and subsequent comminution of ibuprofen crystals by air jet milling.

Crystal morphology plays an important role in drug processing and delivery, which may be controlled during crystallisation. In this study, ibuprofen particles with different size and morphology were produced by controlled crystallisation in order to evaluate their impact on particle size reduction. Results suggest that the micronisation behaviour of ibuprofen was markedly influenced by the morphology and size of starting materials. It was possible to reduce the size of ibuprofen particles to sizes less than 5 µm during dry milling, which is markedly below the reported brittle-ductile transition size. Results also indicate that the particle size reduction mechanism is influenced by the size and morphology of the starting ibuprofen crystals. Dissolution behaviour of ibuprofen was shown to be influenced by the solid surface chemistry of micronised drug particles. The molecular modelling study provided deeper understanding of the experimental findings observed in this study.