Characterization of asbestos exposures associated with the use of facial makeups.

There has been renewed interest in the safety of cosmetics that may contain asbestos or other elongate mineral particles at very low levels as a naturally occurring contaminant. The authors evaluated asbestos exposure during the application of facial makeups in a constructed chamber simulating a bathroom space. The facial makeups tested included products previously found to have very low or "trace" asbestos content by governmental and commercial laboratories using a variety of bulk analysis methods. Tremolite asbestos was detected in five of 54 personal air samples and three of 72 area air samples in 18 simulations. The calculated geometric mean and 95th percentile task-based asbestos concentration associated with personal facial makeup use in this study, incorporating censored data, is 0.0015 and 0.0018 fiber per cubic centimeter (f/cc), respectively, with a corresponding 95th percentile 24-h time-weighted average (TWA) asbestos concentration of 0.00008 f/cc for three applications per day in a simulated bathroom with no active ventilation. Based on these results, cumulative non-occupational asbestos exposures confer a less than one in 1,000,000 risk of asbestos-related disease based on many typical usage patterns and less than 1/100,000 risk with upper-end lifetime usage patterns, using the US Environmental Protection Agency asbestos risk model.

Regioselectivity of Hydroxyl Radical Reactions with Arenes in Nonaqueous Solutions.

The regioselectivity of hydroxyl radical addition to arenes was studied using a novel analytical method capable of trapping radicals formed after the first elementary step of reaction, without alteration of the product distributions by secondary oxidation processes. Product analyses of these reactions indicate a preference for o- over p-substitution for electron donating groups, with both favored over m-addition. The observed distributions are qualitatively similar to those observed for the addition of other carbon-centered radicals, although the magnitude of the regioselectivity observed is greater for hydroxyl. The data, reproduced by high accuracy CBS-QB3 computational methods, indicate that both polar and radical stabilization effects play a role in the observed regioselectivities. The application and potential limitations of the analytical method used are discussed.

Reactivity of Hydroxyl Radical in Nonaqueous Phases: Addition Reactions.

The effect of ring substitution on the kinetics of reaction of arenes, heterocycles, and alkenes with hydroxyl radical is investigated in terms of reactivity and selectivity, using laser flash photolysis (LFP) in acetonitrile solution. The LFP data indicate that charge-transfer contributions in the transition state play an important role in dictating reactivity, and there is a correlation between the experimental and calculated ionization potentials of the arenes and alkenes and their respective reactivities. The reactivity observed for arenes in acetonitrile exhibits a much greater sensitivity toward substitution on the ring than in water, and therefore aqueous data cannot be used to predict reactivity in nonaqueous environments. Nonaqueous solution data may be predictable from gas phase data, and vice versa.

A Laser Flash Photolysis Study of Azo-Compound Formation from Aryl Nitrenes at Room Temperature.

The species 4-nitrenopyridine 1-oxide is known to exhibit triplet nitrene dominated chemistry to yield azo-dimer products exclusively, even at room temperature. As such, this species, and its analogue 4-nitrenoquinoline 1-oxide, are useful models to probe the mechanism of formation of azo-dimers, which is postulated to proceed by self-reaction of the nitrene or reaction of nitrene with the parent azide. A laser flash photolysis study is described where the kinetics of formation of azo-dimer were found to be most adequately modeled by competition between both mechanisms, and rate coefficients for the competing reactions were determined.

A model to systematically employ professional judgment in the Bayesian Decision Analysis for a semiconductor industry exposure assessment.

Bayesian Decision Analysis (BDA) uses Bayesian statistics to integrate multiple types of exposure information and classify exposures within the exposure rating categorization scheme promoted in American Industrial Hygiene Association (AIHA) publications. Prior distributions for BDA may be developed from existing monitoring data, mathematical models, or professional judgment. Professional judgments may misclassify exposures. We suggest that a structured qualitative risk assessment (QLRA) method can provide consistency and transparency in professional judgments. In this analysis, we use a structured QLRA method to define prior distributions (priors) for BDA. We applied this approach at three semiconductor facilities in South Korea, and present an evaluation of the performance of structured QLRA for determination of priors, and an evaluation of occupational exposures using BDA. Specifically, the structured QLRA was applied to chemical agents in similar exposure groups to identify provisional risk ratings. Standard priors were developed for each risk rating before review of historical monitoring data. Newly collected monitoring data were used to update priors informed by QLRA or historical monitoring data, and determine the posterior distribution. Exposure ratings were defined by the rating category with the highest probability--i.e., the most likely. We found the most likely exposure rating in the QLRA-informed priors to be consistent with historical and newly collected monitoring data, and the posterior exposure ratings developed with QLRA-informed priors to be equal to or greater than those developed with data-informed priors in 94% of comparisons. Overall, exposures at these facilities are consistent with well-controlled work environments. That is, the 95th percentile of exposure distributions are ≤50% of the occupational exposure limit (OEL) for all chemical-SEG combinations evaluated; and are ≤10% of the limit for 94% of chemical-SEG combinations evaluated.

Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice.

Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO(2) = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO(2) = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO(2) = 0.10. Plasma catecholamines also increased inversely with FiO(2). Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO(2) = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [(3)H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-γ, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.

Dark-enhanced startle responses and heart rate variability in a traumatized civilian sample: putative sex-specific correlates of posttraumatic stress disorder.

OBJECTIVE: Trauma is associated with increased risk for anxiety disorders such as posttraumatic stress disorder (PTSD). To further understand biologic mechanisms of PTSD, we examined the dark-enhanced startle response, a psychophysiological correlate of anxiety, and heart rate variability (HRV) in traumatized individuals with and without PTSD. The associations of these measures with PTSD may be sex-specific because of their associations with the bed nucleus of the stria terminalis, a sexually dimorphic brain structure in the limbic system that is approximately 2.5 times larger in men than in women. METHODS: The study sample (N = 141) was recruited from a highly traumatized civilian population seeking treatment at Grady Memorial Hospital in Atlanta, Georgia. Psychophysiological responses during a dark-enhanced startle paradigm task included startle magnitude, assessed by eyeblink reflex, and measures of high-frequency HRV, during light and dark phases of the startle session. RESULTS: The startle magnitude was higher during the dark phase than the light phase (mean ± standard error = 98.61 ± 10.68 versus 73.93 ± 8.21 µV, p < .001). PTSD was associated with a greater degree of dark-enhanced startle in women (p = .03) but not in men (p = .38, p interaction = .48). Although HRV measures did not differ between phases, high-frequency HRV was greater in men with PTSD compared with men without PTSD (p = .02). CONCLUSIONS: This study demonstrates that the dark-enhanced paradigm provides novel insights into the psychophysiological responses associated with PTSD in traumatized civilian sample. Sex differences in altered parasympathetic and sympathetic function during anxiety regulation tasks may provide further insight into the neurobiological mechanisms of PTSD.

Physiological markers of anxiety are increased in children of abused mothers.

BACKGROUND: A growing number of studies indicate that low income, African American men and women living in urban environments are at high risk for trauma exposure, which may have intergenerational effects. The current study employed psychophysiological methods to describe biomarkers of anxiety in children of traumatized mothers. METHODS: Study participants were recruited from a highly traumatized urban population, comprising mother-child pairs (n=36) that included school-age children. Mothers were assessed for childhood abuse with the Childhood Trauma Questionnaire, as well as symptoms of depression and posttraumatic stress disorder (PTSD). The children were measured for dark-enhanced startle responses and heart-rate variability. RESULTS: Dark-enhanced startle was found to be higher in children whose mothers had high levels of childhood physical abuse, as compared to children whose mothers had low levels of physical abuse. During the habituation phase of the startle experiment, children whose mothers had high levels of childhood emotional abuse had higher sympathetic system activation compared to children of mothers with low emotional abuse. These effects remained significant after accounting for maternal symptoms of PTSD and depression, as well as for the child's trauma exposure. CONCLUSION: These results demonstrate that children of mothers who have history of childhood physical and emotional abuse have higher dark-enhanced startle as well as greater sympathetic nervous system activation than children of mothers who do not report a history of childhood physical and emotional abuse, and emphasize the utility of physiological measures as pervasive biomarkers of psychopathology that can easily be measured in children.

Hammett correlations in the chemistry of 3-phenylpropyl radicals.

The energetics and kinetics of the reaction of variously substituted benzyl radicals with a model alkene were calculated at the G3(MP2)-RAD//B3-LYP/6-31G(d) level of theory to determine whether such reactions are amenable to Hammett analysis. The reactions were studied both in the gas phase and in toluene solution in the temperature range 298-353 K; calculations include 1D-hindered rotor corrections for low frequency torsional modes, and the solvation energies were calculated using COSMO-RS at the BP/TZP level of theory. The addition reaction was found to be dominated by radical stabilization effects, but under circumstances where olefin substituent effects were decoupled from aryl substituent effects, a modest polar effect comes into play, which is enhanced by solvation. Reasonable correlations with empirical substituent parameters such as Hammett σ and σ(•) are observed for the enthalpy of activation, but additional entropic factors act to decrease the degree of correlation with respect to free energies and rate coefficients, confirming hypotheses from earlier experimental work. Substituent effects on the reverse ß-fragmentation reaction, and potential cyclization of the 3-phenylpropyl radicals formed by addition are also discussed.

Computational study of the chemistry of 3-phenylpropyl radicals.

Density functional theory (DFT) and G3-type (G3(MP2)-RAD) composite calculations were performed on a series of substituted 3-phenylpropyl radicals, to determine the relative importance of fragmentation and cyclization reactions in the chemistry of such species. Our studies indicate that cyclization is generally the more important of these reactions, with exceptions where fragmentation yields highly stabilized benzylic species. The energetic barriers for the cyclization reactions (enthalpies of activation) were found to be determined largely by the stability of the reactant radical and to a lesser but significant extent, by steric factors. Polarity effects in the transition state (modeled by SOMO-LUMO gaps of the products) appear to be less important. The data obtained indicated that the addition of benzyl radical to alkenes may be considered to be irreversible, but calculations for α-substituted styrenic systems indicate that reversibility of addition may become a factor in dilute polymerizing solutions for select systems.

An Intervention to Promote Sleep and Reduce ADHD Symptoms.

OBJECTIVE: To determine the effect of a sleep hygiene education module and prescriptive sleep routine for children ages 5 through 11 years with attention deficit hyperactivity disorder (ADHD). METHODS: The 20-week pilot project used a pre-/posttest design to assess sleep and ADHD symptoms. The Child Sleep Habits Questionnaire (CHSQ) and Vanderbilt Assessment Scale-Parent Form survey were provided to assess sleep and ADHD behaviors of participants at baseline and 6 weeks after implementation of the sleep hygiene routine. Fifty-three children participated in the project. Of these, 23 scored 42 or greater on the CHSQ, indicating a sleep disorder, and received the intervention. RESULTS: The CHSQ and Vanderbilt scores indicated a significant improvement in sleep quality and reduction in ADHD symptoms after implementation of the sleep hygiene routine (CHSQ: p < .001, d = .928; Vanderbilt Questions 1-9: p < .001, d = .473; Vanderbilt Questions 10-18: p = .004; d = .329). CONCLUSION: A provider-instructed sleep hygiene routine in children with ADHD improves sleep quality and reduces ADHD symptoms.

Exposure Reconstruction and Risk Analysis for Six Semiconductor Workers With Lymphohematopoietic Cancers.

OBJECTIVE: To investigate whether workplace exposures to recognized lymphohematopoietic carcinogens were possibly related to cancers in six semiconductor-manufacturing workers. METHODS: A job-exposure matrix was developed for chemical and physical process agents and anticipated by-products. Potential cumulative occupational exposures of the six cases were reconstructed. The role of workplace exposures in cancer was evaluated through quantitative risk assessment and by comparison with epidemiological literature. RESULTS: Two workers were potentially exposed to agents capable of causing their diagnosed cancers. Reconstructed exposures were similar to levels in outdoor environments and lower than exposures associated with increased risks in epidemiological studies. Cancer risks were estimated to be less than 1 in 10,000 persons. CONCLUSIONS: The development of cancer among the six workers was unlikely to be explained by occupational exposures to recognized lymphohematopoietic carcinogens.

Photochemical electron transfer reactions of tirapazamine.

The absorption and fluorescence spectra of 3-aminobenzo-1,2,4-triazine di-N-oxide (tirapazamine) have been recorded and exhibit a dependence on solvent that correlates with the Dimroth ET30 parameter. Time-dependent density functional theory calculations reveal that the transition of tirapazamine in the visible region is pi-->pi* in nature. The fluorescence lifetime is 98+/-2 ps in water. The fluorescence quantum yield is approximately 0.002 in water. The fluorescence of tirapazamine is efficiently quenched by electron donors via an electron-transfer process. Linear Stern-Volmer fluorescence quenching plots are observed with sodium azide, potassium thiocyanate, guanosine monophosphate and tryptophan (Trp) methyl ester hydrochloride. Guanosine monophosphate, tyrosine (Tyr) methyl ester hydrochloride and Trp methyl ester hydrochloride appear to quench the fluorescence at a rate greater than diffusion control implying that these substrates complex with tirapazamine in its ground state. This complexation was detected by absorption spectroscopy.

Longitudinal changes in total body creatine pool size and skeletal muscle mass using the D3-creatine dilution method.

BACKGROUND: We recently validated in cross-sectional studies a new method to determine total body creatine pool size and skeletal muscle mass based on D3-creatine dilution from an oral dose and detection of urinary creatinine enrichment by isotope ratio mass spectrometry (IRMS). Routine clinical use of the method in aging and disease will require repeated application of the method, with a more widely available technology than IRMS, to enable determination of change in skeletal muscle mass in longitudinal studies. We therefore adapted the method to liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, and sought to establish proof of concept for the repeated application of the method in a longitudinal study. Because the turnover of creatine is slow, it was also critical to determine the impact of background enrichment from an initial dose of oral D3-creatine on subsequent, longitudinal measurements of change in muscle mass. METHODS: Rats were given an oral tracer dose of D3-creatine (1.0 mg/kg body weight) at 10 and 17 weeks of age. LC-MS/MS was used to determine urinary D3-creatine, and urinary D3-creatinine enrichment, at time intervals after D3-creatine administration. Total body creatine pool size was calculated from urinary D3-creatinine enrichment at isotopic steady state 72 h after administration of D3-creatine tracer. RESULTS: At 10 weeks of age, rat lean body mass (LBM) measured by quantitative magnetic resonance correlated with creatine pool size (r = 0.92, P = 0.0002). Over the next 7 weeks, the decline in urinary D3-creatinine enrichment was slow and linear, with a rate constant of 2.73 ± 0.06 %/day. Subtracting background urinary D3-creatinine enrichment from the elevated enrichment following a second dose of D3-creatine at 17 weeks permitted repeat calculations of creatine pool size. As at 10 weeks, 17-week LBM correlated with creatine pool size (r = 0.98, P <0.0001). In addition, the change in creatine pool size was correlated with the change in LBM during the 7 weeks of rat growth between measurements (r = 0.96, P <0.0001). CONCLUSION: The LC-MS/MS-based D3-creatine dilution method can be applied repeatedly to measure total body creatine skeletal muscle mass change in longitudinal study.

Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-D3) dilution in rats.

There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (<1 mg/rat) was >99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P < 0.0001), and corresponded to predicted total muscle mass. Total-body creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass.

Psychotherapy appointment no-shows: rates and reasons.

Patients who frequently miss or do not show for their scheduled psychotherapy appointments create administrative and clinical difficulties, and may not be receiving effective treatment. Prior research has predominately focused on either identifying demographic and administrative factors related to patient no-show rates or evaluating the effectiveness of administrative procedures for reducing no-shows. This paper attempts to identify rates of missed appointments in clinical practice and explore more specific clinical process factors related to patient no-shows. Psychotherapists (N = 24) and their patients (N = 542) in the outpatient department of a public safety-net hospital were surveyed to examine how frequently patients missed scheduled psychotherapy appointments and for what reasons. Findings indicate that the majority of missed appointments were accounted for by patients with occasional absences (approx. 1 per month), while only a small percentage of patients missed appointments with high frequency. Patients missed their psychotherapy appointments for a number of reasons, including clinical symptoms, practical matters, motivational concerns, and negative treatment reactions.

Comparative study of the photochemistry of the azidopyridine 1-oxides.

The photochemistry of azidopyridine 1-oxides was studied using an array of glass and matrix isolation techniques. As with room temperature, the photochemistry of 4-azidopyridine 1-oxide is dominated by triplet nitrene chemistry. However, in the case of the 3-azide, matrix photolysis indicates the formation of diazabicyclo[4.1.0]hepta-2,4,6-triene N-oxide and diazacycloheptatetraene N-oxide intermediates as well as triplet nitrene.

The photochemistry of 4-azidopyridine-1-oxide.

Laser flash photolysis of 4-azidopyridine-1-oxide at 266 or 308 nm yields triplet 4-nitrenopyridine-1-oxide as the dominant reactive intermediate species, with k(ISC) of approximately 2 x 10(7) s(-1). No evidence of products arising from the singlet nitrene was observed, indicating a slow rate of cyclization to the benzazirine and didehydroazepine species. The slow rate of cyclization is postulated to be due to the aminoxyl-like electronic configuration of this species, which withdraws spin density from sites for potential cyclization.

Time-resolved spectroscopy of the excited singlet states of tirapazamine and desoxytirapazamine.

Laser flash photolysis (LFP, 400 nm excitation) of the anti-cancer drug tirapazamine (TPZ) in acetonitrile produces the singlet excited-state S1 with lambda(max) = 544 nm. The lifetime of this state is 130 ps, in good agreement with the reported fluorescence lifetime. The excited state is reduced to the corresponding radical anion by KSCN or KI. The spectrum of the radical anion is in good agreement with previously reported pulse radiolysis studies and time-dependent density functional theory (TD-DFT) calculations. LFP of desoxytirapazamine (dTPZ) also produces the first excited singlet state, S1. The fluorescence quantum yield and lifetime (5.4 ns) of the dTPZ singlet excited state are both much greater than the corresponding values of TPZ. This is explained by DFT calculations that predict that cyclization of TPZ to form an oxaziridine is thermodynamically facile but that cyclization of dTPZ to form an oxadiaziridine is not. Thus, the S1 state of TPZ has a short lifetime and low fluorescence quantum yield due to ready cyclization whereas the cyclization of the S1 state of dTPZ is unimportant and does not limit either the fluorescence quantum yield or the fluorescence lifetime. This conclusion is confirmed by studies of dTPZ', an isomer of dTPZ containing the C=N-O moiety which has a low quantum yield and short fluorescence lifetime similar to that of TPZ.