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The toxicokinetic behavior of α-pinene and its potential reactive metabolite, α-pinene oxide, was investigated following whole body inhalation exposure to 50 and 100 ppm α-pinene in rats and mice for 6 h per day for 7d. In both species and sexes, the maximum blood concentration (Cmax) increased more than proportionally while the increase in area under the concentration time curve (AUC) was proportional to the exposure concentration. When normalized to the calculated dose (D), both Cmax/D (male rats, 12.2–54.5; female rats, 17.4–74.1; male mice, 7.41–14.2; female mice, 6.59–13.0 (ng/mL)/(mg/kg)) and AUC/D (male rats, 28.9–31.1; female rats, 55.8–56.8; male mice, 18.1–19.4; female mice, 19.2–22.5 (h*ng/mL)/(mg/kg)) in rats were higher than in mice and in female rats were higher than in male rats; no sex difference was observed in mice. α-Pinene was eliminated from blood with half-lives between 12.2 and 17.4 h in rats and 6.18–19.4 h in mice. At the low dose, the ratio of α-pinene oxide to α-pinene, based on Cmax and AUC, respectively, was 0.200–0.237 and 0.279–0.615 in rats and 0.060–0.086 and 0.036–0.011 in mice demonstrating lower formation of the oxide in mice than in rats. At the high dose, the ratio decreased considerably in both species pointing to saturation of pathways leading to the formation of α-pinene oxide. α-Pinene and the oxide were quantified in the mammary glands of rats and mice with tissue to blood ratios of ≥23 demonstrating retention of these analytes in mammary glands. The findings of epoxide formation and species- and sex-differences in systemic exposure may be important in providing context and relating animal findings to human exposures.

Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg-1 ) or by gavage (p.o.) (10 mg kg-1 ), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (μg Ag g-1 tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest concentration was measured in the cecum and large intestine, and for AgAc in the placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver. Copyright © 2016 John Wiley & Sons, Ltd.

Introduction Few studies have examined the best use of admission data to differentiate between successful and unsuccessful students in a nursing program. Methods Using data from 341 students admitted over a 3-year period, the authors attempted to determine which factors best predicted student success in a baccalaureate of science in nursing, or BSN, program. These factors were used to develop an admission formula that was tested retroactively to determine its ability to differentiate between successful and unsuccessful students. The authors defined student success as passing all nursing courses on the first attempt with a grade of C or above, completing the program on time, and passing the National Council Licensure Examination on the first attempt. Logistic regression for prediction of the probability of success found that the following three variables accounted for 76% of the variance: preprogram grade point average, or GPA, science GPA, and scores on the Health Educational Systems Incorporated Admission Assessment anatomy and physiology subscale. The formula derived was validated by retrospective analysis to determine effect of using this model to select students for admission. Results Use of this model would have eliminated 40.9% of the unsuccessful students and retained 84% of the successful students. Conclusion The formula derived from this study is now being used to select students for the BSN program. In the future, graduation rates obtained by using this formula will be compared to the graduation rates obtained by the prior rational admission process.

2-Arylpyrrolidines occur frequently in bioactive compounds, and thus, methods to access them from readily available reagents are valuable. We report a copper-catalyzed intermolecular carboamination of vinylarenes with potassium N-carbamoyl-β-aminoethyltrifluoroborates. The reaction occurs with terminal, 1,2-disubstituted, and 1,1-disubstituted vinylarenes bearing a number of functional groups. 1,3-Dienes are also good substrates, and their reactions give 2-vinylpyrrolidines. Radical clock mechanistic experiments are consistent with the presence of carbon radical intermediates and do not support participation of carbocations.

Poverty lack of resources and pervasive adversity threaten the healthy social and emotional development of many children living in rural Appalachia. Despite these traumatic stressors, however, Appalachian residents have proven surprisingly resilient and responsive to intervention. This article describes the twin efforts of the Partnerships Program for Early Childhood Mental Health and Project LAUNCH, a community-university-state initiative, to transform school systems by establishing enduring partnerships within and across schools and agencies, pooling and disseminating critical resources, and strengthening the skills, confidence and capacity of the early childhood education workforce. This article describes the three-tiered framework of services implemented at the schools, with special emphasis on its trauma-informed training for educators combined with trauma-specific mental health interventions delivered on site. Despite a modest sample size, results indicate significant pre-improvement/post-improvement in teacher confidence and hopefulness in positively impacting challenging child behaviors; a decrease in the negative attributes of the preschool learning environment; and increased teacher ratings of child resilience as measured by the Devereux Early Child Assessment. Program limitations and future directions for creating trauma-informed Appalachian schools are discussed.

Bisphenol S (BPS) is a component of polyether sulfone used in a variety of industrial applications and consumer products. We investigated the plasma toxicokinetic (TK) behavior of free (unconjugated parent) and total (parent and conjugated) BPS in rats and mice following a single gavage administration (34, 110, or 340 mg/kg). In male rats, BPS was rapidly absorbed with free BPS maximum concentration (C(max)) reached at ≤ 2.27 h. Elimination of free BPS in male rats was dose-dependent with estimated half-lives of 5.77–11.9 h. C(max) and area under the concentration versus time curve (AUC) increased with dose although the increase in AUC was more than dose proportional. In male rats, total BPS C(max) was reached ≤ 2.77 h with both C(max) (≥ 10-fold) and AUC (≥ 15-fold) higher than free BPS demonstrating rapid and extensive conjugation of BPS. In male mice, the increase in C(max) and AUC of free BPS was dose-proportional; C(max) was higher and AUC was lower than in male rats. BPS was cleared more rapidly in male mice (half-life 2.86–4.21 h) compared to male rats (half-life 5.77– 11.9 h). Similar to rats, total BPS C(max) (≥ 6-fold) and AUC (≥ 12-fold) were higher than corresponding free BPS. Oral bioavailability of free BPS was low to moderate (rats, ≤ 21%; mice, ≤ 19%). There were some species differences in TK parameters of free and total BPS and limited sex difference in rats and mice. In addition, there were dose-related effects of plasma TK parameters in rats.

Date Presented 03/26/20 The OT project used a mixed design to determine the impact of consultation OT services in a faith-based preschool. Teachers were educated on motor-skill development and methods to create motor opportunities within classroom routines. Postproject, teachers indicated improved confidence to incorporate motor activities into preschool routines. The project identified that community-based preschools should be an area of focus for OT practitioners. Primary Author and Speaker: Sherry Stancliff

Enantiomerically enriched phthalans were synthesized efficiently via an enantioselective copper-catalyzed alkene carboetherification reaction. In this reaction, 2-vinylbenzyl alcohols enantioselectively cyclize then couple with vinylarenes. The utility of the method was demonstrated by the enantioselective synthesis of (R)-fluspidine, a σ(1) receptor ligand.

A new copper-catalyzed enantioselective aza-Freidel-Crafts reaction between phenols and N-sulfonyl aldimines that provides chiral secondary benzylamines in good to excellent yields and excellent enantioselectivities (up to 99% ee) is disclosed. In particular, excellent scope with alkylimines was observed for the first time. The synthetic utility of the products was demonstrated in the first enantioselective synthesis of a dual orexin receptor antagonist, a compound that contains an amine-bearing stereocenter adjacent to a bis- ortho-functionalized arene.

We, the North City Area Wide Council, Inc., believe this is a unique case study. It has been put together by community people for the benefit of other community people. Although it will be widely read by policy makers and politicians, it is addressed only to people like ourselves who are struggling against impossible odds to make public programs relevant to poor and powerless people.

With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [14C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [14C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention.

Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental relevance. Both intravenous and oral dosing were used to calculate bioavailability. These chemicals, and an additional 19 chemicals (including some pharmaceuticals) from previously published in vivo rat studies, were systematically analyzed to estimate in vivo TK parameters (e.g., volume of distribution [Vd], elimination rate). For each of the chemicals, rat-specific HTTK data were available and key TK predictions were examined: oral bioavailability, clearance, Vd, and uncertainty. For the non-pharmaceutical chemicals, predictions for bioavailability were not effective. While no pharmaceutical was absorbed at less than 10%, the fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%. Total clearance was generally more underestimated for nonpharmaceuticals and Vd methods calibrated to pharmaceuticals may not be appropriate for other chemicals. However, the steady-state, peak, and time-integrated plasma concentrations of nonpharmaceuticals were predicted with reasonable accuracy. The plasma concentration predictions improved when experimental measurements of bioavailability were incorporated. In summary, HTTK and IVIVE methods are adequately robust to be applied to high throughput in vitro toxicity screening data of environmentally relevant chemicals for prioritizing based on human health risks. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

1. Tris(4-chlorophenyl)methane (TCPME) and Tris(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues. 2. The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice. 3. [14C]TCPME was well absorbed (≥ 66%) in male rats and mice following a single oral administration of 1, 10, or 100 mg/kg. The excretion of [14C]TCPME-derived radioactivity in urine (≤ 2.5%) and feces (≤18%) was low. The administered dose was retained in tissues (≥ 64%) with adipose containing the highest concentrations. The metabolism of TCPME was minimal. The disposition and metabolism of [14C]TCPME in females was similar to males. 4. The time to reach maximum concentration was ≤7 h, the plasma elimination half-life was ≥ 31 h, and the bioavailability was ≥ 82% following a 10 mg/kg oral dose of [14C]TCPME in male rats and mice. 5. The disposition of [14C]TCPMOH was similar to that of [14C]TCPME. 6. Following an intravenous administration of [14C]TCPME or [14C]TCPMOH in male rats and mice, the pattern of disposition was similar to that of oral administration. 7. In conclusion, both TCPME and TCPMOH are readily absorbed and highly bioavailable following a single oral administration pointing to importance of assessing the toxicity of these chemicals.

Tris(4-chlorophenyl)methane (TCPME) and tris(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues.The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice.[14C]TCPME was well absorbed (≥66%) in male rats and mice following a single oral administration of 1, 10, or 100 mg/kg. The excretion of [14C]TCPME-derived radioactivity in urine (≤2.5%) and feces (≤18%) was low. The administered dose was retained in tissues (≥ 64%) with adipose containing the highest concentrations. The metabolism of TCPME was minimal. The disposition and metabolism of [14C]TCPME in females was similar to males.The time to reach maximum concentration was ≤7 h, the plasma elimination half-life was ≥31 h, and the bioavailability was ≥82% following a 10 mg/kg oral dose of [14C]TCPME in male rats and mice.The disposition of [14C]TCPMOH was similar to that of [14C]TCPME.Following an intravenous administration of [14C]TCPME or [14C]TCPMOH in male rats and mice, the pattern of disposition was similar to that of oral administration.In conclusion, both TCPME and TCPMOH are readily absorbed and highly bioavailable following a single oral administration pointing to importance of assessing the toxicity of these chemicals. Tris(4-chlorophenyl)methane (TCPME) and tris(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues. The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice. [14C]TCPME was well absorbed (≥66%) in male rats and mice following a single oral administration of 1, 10, or 100 mg/kg. The excretion of [14C]TCPME-derived radioactivity in urine (≤2.5%) and feces (≤18%) was low. The administered dose was retained in tissues (≥ 64%) with adipose containing the highest concentrations. The metabolism of TCPME was minimal. The disposition and metabolism of [14C]TCPME in females was similar to males. The time to reach maximum concentration was ≤7 h, the plasma elimination half-life was ≥31 h, and the bioavailability was ≥82% following a 10 mg/kg oral dose of [14C]TCPME in male rats and mice. The disposition of [14C]TCPMOH was similar to that of [14C]TCPME. Following an intravenous administration of [14C]TCPME or [14C]TCPMOH in male rats and mice, the pattern of disposition was similar to that of oral administration. In conclusion, both TCPME and TCPMOH are readily absorbed and highly bioavailable following a single oral administration pointing to importance of assessing the toxicity of these chemicals.

1. Bisphenol AF (BPAF) is used as a crosslinking agent for polymers and is being considered as a replacement for bisphenol A (BPA). 2. In this study, comparative clearance and metabolism of BPAF and BPA in hepatocytes and the disposition and metabolism of BPAF in rodents following oral administration of 3.4, 34 or 340 mg/kg [(14)C]BPAF were investigated. 3. BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat mouse human. 4. [(14)C]BPAF was excreted primarily in feces by 72 h after oral administration to rats (65-80%) and mice (63-72%). Females excreted more in urine (rat, 15%; mouse, 24%) than males (rat, 1-4%; mouse, 10%). Residual tissue radioactivity was2% of the dose at 72 h. Similar results were observed following intravenous administration. 5. In male rats, 52% of a 340 mg/kg oral dose was excreted in 24 h bile and was mostly comprised of BPAF glucuronide. However,94% of fecal radioactivity was present as BPAF, suggesting extensive deconjugation in the intestine. 6. Metabolites identified in bile were BPAF-glucuronide, -diglucuronide, -glucuronide sulfate and -sulfate. 7. In conclusion, BPAF was well absorbed following gavage administration and highly metabolized and excreted mostly in the feces as BPAF.

Each year, up to one fifth of the United States population is infected with influenza virus. Although mortality rates are low, hundreds of thousands are hospitalized each year in the United States. Specific high risk groups, such as those with suppressed or dysregulated immune systems, are at greater danger for influenza complications. Respiratory infections are a common cause of hospitalizations and early mortality in patients with systemic lupus erythematosus (SLE); however, whether this increased infection risk is a consequence of the underlying dysregulated immune background and/or immunosuppressing drugs is unknown. To evaluate the influenza immune response in the context of lupus, as well as assess the effect of infection on autoimmune disease in a controlled setting, we infected lupus-prone MRL/MpJ-Fas(lpr) mice with influenza virus A PR/8/34 H1N1. Interestingly, we found that Fas(lpr) mice generated more influenza A virus specific T cells with less neutrophil accumulation in the lung during acute infection. Moreover, Fas(lpr) mice produced fewer flu-specific IgG and IgM antibodies, but effectively cleared the virus. Further, increased extrinsic apoptosis during influenza infection led to a delay in autoimmune disease pathology with decreased severity of splenomegaly and kidney disease. Following primary influenza A infection, Fas(lpr) mice had severe complications during the contraction and resolution phase with widespread severe pulmonary inflammation. Our findings suggest that influenza infection may not exacerbate autoimmune pathology in mice during acute infection as a direct result of virus induced apoptosis. Additionally, autoimmunity drives an enhanced antigen-specific T cell response to clear the virus, but persisting pulmonary inflammation following viral clearance may cause complications in this lupus animal model.

Background . Since 2002, No Child Left Behind has caused administrators to place great emphasis on academic learning, particularly for students of low income. This has practitioners seeking strategies that will produce student academic growth, yet few are looking to bolster student-teacher relationships, a strategy that has shown promise in the areas of student achievement, student behavior, for students of differing abilities and in different types of schools and situations. Purpose . The purpose of this study was to reveal teacher attributes or characteristics, which were valued by fifth grade students from poverty and affluent schools in a rural midwestern community. Method . Research was conducted using a mixed-methods approach, with the primary data collected from 24 semi-structured student interviews. Results . Results revealed seven teacher attributes that were valued by students. The characteristics included consistent help (with high expectations); a sense of humor; active listening, providing for a sense of community, and several others. Conclusions . The identification of these attributes provides goals for personal development by teachers, regardless of the socio-economic composition of the school where they work. Additionally, these attributes could assist administrators and other hiring officials for school districts in searching for potentially successful hirees, as well as provide a foundation around which a perceiver survey could be developed.