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Objective: To present a case report and to propose an anatomic explanation for a rare complication of tonsillectomy, severe dysphagia caused by bilateral paralysis of the glossopharyngeal nerve. Study Design: Retrospective case review and prospective cadaveric dissection. Methods: The medical record and radiologic data were reviewed from a patient who had severe dysphagia after tonsillectomy. In addition, 10 formalin-preserved cadaver head and neck specimens were dissected to identify the anatomic course of 20 glossopharyngeal nerves. The distance between the nerve and tonsillar fossa was measured at two sites. Results: The patient was diagnosed with bilateral paralysis of the glossopharyngeal nerve and required use of gastrotomy tube for years postoperatively. The mean distance from the posterosuperior tonsillar fossa and the main trunk of the glossopharyngeal nerve was 10.7 mm, and the mean distance from the posteroinferior tonsillar fossa and the closest lingual branch of the glossopharyngeal nerve was 6.5 mm. Conclusions: Direct nerve injury seems the most plausible explanation for this rare complication of tonsillectomy. The proximity of the glossopharyngeal nerve to the tonsillar fossa emphasizes the importance of maintaining the correct surgical plane during surgery. [ABSTRACT FROM AUTHOR]

The author encourages nurse practitioners to apply historical thoughts to create a vision for the future. She reflects on the history of professional nursing and public health nursing. She expresses her views on public health and the role of nursing practitioners in primary health care. The author also urges nurse practitioners to prove themselves clinically and be unified in advancing nursing care.

Per- and poly-fluoroalkyl substances (PFAS) are emerging contaminants of concern because of their wide use, persistence, and potential to be hazardous to both humans and the environment. Several PFAS have been designated as substances of concern; however, most PFAS in commerce lack toxicology and exposure data to evaluate their potential hazards and risks. Cardiotoxicity has been identified as a likely human health concern, and cell-based assays are the most sensible approach for screening and prioritization of PFAS. Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a widely used method to test for cardiotoxicity, and recent studies showed that many PFAS affect these cells. Because iPSC-derived cardiomyocytes are available from different donors, they also can be used to quantify human variability in responses to PFAS. The primary objective of this study was to characterize potential human cardiotoxic hazard, risk, and inter-individual variability in responses to PFAS. A total of 56 PFAS from different subclasses were tested in concentration-response using human iPSC-derived cardiomyocytes from 16 donors without known heart disease. Kinetic calcium flux and high-content imaging were used to evaluate biologically-relevant phenotypes such as beat frequency, repolarization, and cytotoxicity. Of the tested PFAS, 46 showed concentration-response effects in at least one phenotype and donor; however, a wide range of sensitivities were observed across donors. Inter-individual variability in the effects could be quantified for 19 PFAS, and risk characterization could be performed for 20 PFAS based on available exposure information. For most tested PFAS, toxicodynamic variability was within a factor of 10 and the margins of exposure were above 100. This study identified PFAS that may pose cardiotoxicity risk and have high inter-individual variability. It also demonstrated the feasibility of using a population-based human in vitro method to quantify population variability and identify cardiotoxicity risks of emerging contaminants., (© 2024. The Author(s).)

Environmental chemicals may contribute to the global burden of cardiovascular disease, but experimental data are lacking to determine which substances pose the greatest risk. Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a high-throughput cardiotoxicity model that is widely used to test drugs and chemicals; however, most studies focus on exploring electro-physiological readouts. Gene expression data may provide additional molecular insights to be used for both mechanistic interpretation and dose-response analyses. Therefore, we hypothesized that both transcriptomic and functional data in human iPSC-derived cardiomyocytes may be used as a comprehensive screening tool to identify potential cardiotoxicity hazards and risks of the chemicals. To test this hypothesis, we performed concentration-response analysis of 464 chemicals from 12 classes, including both pharmaceuticals and nonpharmaceutical substances. Functional effects (beat frequency, QT prolongation, and asystole), cytotoxicity, and whole transcriptome response were evaluated. Points of departure were derived from phenotypic and transcriptomic data, and risk characterization was performed. Overall, 244 (53%) substances were active in at least one phenotype; as expected, pharmaceuticals with known cardiac liabilities were the most active. Positive chronotropy was the functional phenotype activated by the largest number of tested chemicals. No chemical class was particularly prone to pose a potential hazard to cardiomyocytes; a varying proportion (10-44%) of substances in each class had effects on cardiomyocytes. Transcriptomic data showed that 69 (15%) substances elicited significant gene expression changes; most perturbed pathways were highly relevant to known key characteristics of human cardiotoxicants. The bioactivity-to-exposure ratios showed that phenotypic- and transcriptomic-based POD led to similar results for risk characterization. Overall, our findings demonstrate how the integrative use of in vitro transcriptomic and phenotypic data from iPSC-derived cardiomyocytes not only offers a complementary approach for hazard and risk prioritization, but also enables mechanistic interpretation of the in vitro test results to increase confidence in decision-making.

There are two primary sources of uncertainty in the interpretability of toxicity values, like the reference dose (RfD): estimates of the point of departure (POD) and the absence of chemical-specific human variability data. We hypothesize two solutions-employing Bayesian benchmark dose (BBMD) modeling to refine POD determination and combining high-throughput toxicokinetic modeling with population-based toxicodynamic in vitro data to characterize chemical-specific variability. These hypotheses were tested by deriving refined probabilistic estimates for human doses corresponding to a specific effect size (M) in the Ith population percentile (HD M I ) across 19 Superfund priority chemicals. HD M I values were further converted to biomonitoring equivalents in blood and urine for benchmarking against human data. Compared to deterministic default-based RfDs, HD M I values were generally more protective, particularly influenced by chemical-specific data on interindividual variability. Incorporating chemical-specific in vitro data improved precision in probabilistic RfDs, with a median 1.4-fold reduction in uncertainty variance. Comparison with US Environmental Protection Agency's Exposure Forecasting exposure predictions and biomonitoring data from the National Health and Nutrition Examination Survey identified chemicals with margins of exposure nearing or below one. Overall, to mitigate uncertainty in regulatory toxicity values and guide chemical risk management, BBMD modeling and chemical-specific population-based human in vitro data are essential., (© 2024 The Author(s). Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

In vitro models that can faithfully replicate critical aspects of kidney tubule function such as directional drug transport are in high demand in pharmacology and toxicology. Accordingly, development and validation of new models is underway. The objective of this study was to characterize physiological and transport functions of various sources of human renal proximal tubule epithelial cells (RPTECs). We tested TERT1-immortalized RPTEC, including OAT1-, OCT2- or OAT3-overexpressing variants, and primary RPTECs. Cells were cultured on transwell membranes in static (24-well transwells) and fluidic (transwells in PhysioMimix{trade mark, serif} T12 organ-on-chip with 2 mL/s flow) conditions. Barrier formation, transport, and gene expression were evaluated. We show that two commercially available primary RPTECs were not suitable for studies of directional transport on transwells because they formed a substandard barrier even though they exhibited higher expression of transporters, especially under flow. TERT1-parent, -OAT1 and -OAT3 cells formed robust barriers, but were unaffected by flow. TERT1-OAT1 cells exhibited inhibitable para-aminohippurate transport, it was enhanced by flow. However, efficient tenofovir secretion and perfluorooctanoic acid reabsorption by TERT1-OAT1 cells were not modulated by flow. Gene expression showed that TERT1 and TERT1-OAT1 cells were most correlated with human kidney than other cell lines, but that flow did not have noticeable effects. Overall, our data show that addition of flow to in vitro studies of the renal proximal tubule may afford benefits in some aspects of modeling kidney function, but that careful consideration of the impact such adaptations would have on the cost and throughput of the experiments is needed. Significance Statement The topic of reproducibility and robustness of the complex microphysiological systems is looming large in the field of biomedical research; therefore, the uptake of these new models by the end-users is slow. This study systematically compared various RPTEC sources and experimental conditions, aiming to identify the level of model complexity needed for testing renal tubule transport. We demonstrate that while tissue chips may afford some benefits, their throughput and complexity need careful consideration in each context of use., (U.S. Government Work not Protected by U.S. Copyright.)

Per- and poly-fluoroalkyl substances (PFAS) are extensively used in commerce leading to their prevalence in the environment. Due to their chemical stability, PFAS are considered to be persistent and bioaccumulative; they are frequently detected in both the environment and humans. Because of this, PFAS as a class (composed of hundreds to thousands of chemicals) are contaminants of very high concern. Little information is available for the vast majority of PFAS, and regulatory agencies lack safety data to determine whether exposure limits or restrictions are needed. Cell-based assays are a pragmatic approach to inform decision-makers on potential health hazards; therefore, we hypothesized that a targeted battery of human in vitro assays can be used to determine whether there are structure-bioactivity relationships for PFAS, and to characterize potential risks by comparing bioactivity (points of departure) to exposure estimates. We tested 56 PFAS from 8 structure-based subclasses in concentration response (0.1-100 μM) using six human cell types selected from target organs with suggested adverse effects of PFAS - human induced pluripotent stem cell (iPSC)-derived hepatocytes, neurons, and cardiomyocytes, primary human hepatocytes, endothelial and HepG2 cells. While many compounds were without effect; certain PFAS demonstrated cell-specific activity highlighting the necessity of using a compendium of in vitro models to identify potential hazards. No class-specific groupings were evident except for some chain length- and structure-related trends. In addition, margins of exposure (MOE) were derived using empirical and predicted exposure data. Conservative MOE calculations showed that most tested PFAS had a MOE in the 1-100 range; ∼20% of PFAS had MOE<1, providing tiered priorities for further studies. Overall, we show that a compendium of human cell-based models can be used to derive bioactivity estimates for a range of PFAS, enabling comparisons with human biomonitoring data. Furthermore, we emphasize that establishing structure-bioactivity relationships may be challenging for the tested PFAS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Lucie C. Ford reports financial support was provided by Texas A&M University. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

To fulfil the promise of reducing reliance on mammalian in vivo laboratory animal studies, new approach methods (NAMs) need to provide a confident basis for regulatory decision-making. However, previous attempts to develop in vitro NAMs-based points of departure (PODs) have yielded mixed results, with PODs from U.S. EPA's ToxCast, for instance, appearing more conservative (protective) but poorly correlated with traditional in vivo studies. Here, we aimed to address this discordance by reducing the heterogeneity of in vivo PODs, accounting for species differences, and enhancing the biological relevance of in vitro PODs. However, we only found improved in vitro-to-in vivo concordance when combining the use of Bayesian model averaging-based benchmark dose modeling for in vivo PODs, allometric scaling for interspecies adjustments, and human-relevant in vitro assays with multiple induced pluripotent stem cell-derived models. Moreover, the available sample size was only 15 chemicals, and the resulting level of concordance was only fair, with correlation coefficients <0.5 and prediction intervals spanning several orders of magnitude. Overall, while this study suggests several ways to enhance concordance and thereby increase scientific confidence in vitro NAMs-based PODs, it also highlights challenges in their predictive accuracy and precision for use in regulatory decision making., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Weihsueh A. Chiu reports financial support was provided by National Institute of Environmental Health Sciences. Weihsueh A. Chiu reports financial support was provided by U.S. Environmental Protection Agency. Ivan Rusyn reports financial support was provided by National Institute of Environmental Health Sciences. Ivan Rusyn reports financial support was provided by U.S. Environmental Protection Agency. Lucie C. Ford reports financial support was provided by National Institute of Environmental Health Sciences. Zunwei Chen reports financial support was provided by National Institute of Environmental Health Sciences. Sarah D. Burnett reports financial support was provided by National Institute of Environmental Health Sciences. Sarah D. Burnett reports financial support was provided by U.S. Environmental Protection Agency. Weihsueh A. Chiu reports a relationship with Dreamtech Co Ltd that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are chemicals with important applications; they are persistent in the environment and may pose human health hazards. Regulatory agencies are con­sidering restrictions and bans of PFAS; however, little data exists for informed decisions. Several prioritization strategies were proposed for evaluation of potential hazards of PFAS. Structure-based grouping could expedite the selection of PFAS for testing; still, the hypothesis that structure-effect relationships exist for PFAS requires confirmation. We tested 26 structurally diverse PFAS from 8 groups using human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes, and tested concentration-response effects on cell function and gene expression. Few phenotypic effects were observed in hepatocytes, but negative chronotropy was observed in cardiomyocytes for 8 PFAS. Substance- and cell type-dependent transcriptomic changes were more prominent but lacked substantial group-specific effects. In hepatocytes, we found upregulation of stress-related and extracellular matrix organization pathways, and down-regulation of fat metabolism. In car­diomyocytes, contractility-related pathways were most affected. We derived phenotypic and transcriptomic points of departure and compared them to predicted PFAS exposures. Conservative estimates for bioactivity and exposure were used to derive a bioactivity-to-exposure ratio (BER) for each PFAS; 23 of 26 PFAS had BER > 1. Overall, these data suggest that structure-based PFAS grouping may not be sufficient to predict their biological effects. Testing of individual PFAS may be needed for scientifically-supported decision-making. Our proposed strategy of using two human cell types and considering phenotypic and transcriptomic effects, combined with dose-response analysis and calculation of BER, may be used for PFAS prioritization.

Microphysiological systems are an emerging area of in vitro drug development, and their independent evaluation is important for wide adoption and use. The primary goal of this study was to test reproducibility and robustness of a renal proximal tubule microphysiological system, OrganoPlate 3-lane 40, as an in vitro model for drug transport and toxicity studies. This microfluidic model was compared with static multiwell cultures and tested using several human renal proximal tubule epithelial cell (RPTEC) types. The model was characterized in terms of the functional transport for various tubule-specific proteins, epithelial permeability of small molecules (cisplatin, tenofovir, and perfluorooctanoic acid) versus large molecules (fluorescent dextrans, 60-150 kDa), and gene expression response to a nephrotoxic xenobiotic. The advantages offered by OrganoPlate 3-lane 40 as compared with multiwell cultures are the presence of media flow, albeit intermittent, and increased throughput compared with other microfluidic models. However, OrganoPlate 3-lane 40 model appeared to offer only limited (eg, MRP-mediated transport) advantages in terms of either gene expression or functional transport when compared with the multiwell plate culture conditions. Although OrganoPlate 3-lane 40 can be used to study cellular uptake and direct toxic effects of small molecules, it may have limited utility for drug transport studies. Overall, this study offers refined experimental protocols and comprehensive comparative data on the function of RPETCs in traditional multiwell culture and microfluidic OrganoPlate 3-lane 40, information that will be invaluable for the prospective end-users of in vitro models of the human proximal tubule., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Human cell-based test methods can be used to evaluate potential hazards of mixtures and products of petroleum refining ("unknown or variable composition, complex reaction products, or biological materials" substances, UVCBs). Analyses of bioactivity and detailed chemical characterization of petroleum UVCBs were used separately for grouping these substances; a combination of the approaches has not been undertaken. Therefore, we used a case example of representative high production volume categories of petroleum UVCBs, 25 lower olefin substances from low benzene naphtha and resin oils categories, to determine whether existing manufacturing-based category grouping can be supported. We collected two types of data: nontarget ion mobility spectrometry-mass spectrometry of both neat substances and their organic extracts and in vitro bioactivity of the organic extracts in five human cell types: umbilical vein endothelial cells and induced pluripotent stem cell-derived hepatocytes, endothelial cells, neurons, and cardiomyocytes. We found that while similarity in composition and bioactivity can be observed for some substances, existing categories are largely heterogeneous. Strong relationships between composition and bioactivity were observed, and individual constituents that determine these associations were identified. Overall, this study showed a promising approach that combines chemical composition and bioactivity data to better characterize the variability within manufacturing categories of petroleum UVCBs.

Cell-based testing of multi-constituent substances and mixtures for their potential adverse health effects is difficult due to their complex composition and physical-chemical characteristics. Various extraction methods are typically used to enable studies in vitro; however, a limited number of solvents are biocompatible with in vitro studies and the extracts may not fully represent the original test article's composition. While the methods for dosing with "difficult-to-test" substances in aquatic toxicity studies are well defined and widely used, they are largely unsuited for small-volume (100 microliters or less) in vitro studies with mammalian cells. Therefore, we aimed to evaluate suitability of various scaled-down dosing methods for high-throughput in vitro testing by using a mixture of polycyclic aromatic hydrocarbons (PAH). Specifically, we compared passive dosing via silicone micro-O-rings, cell culture media-accommodated fraction, and traditional solvent (dimethyl sulfoxide) extraction procedures. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to evaluate kinetics of PAH absorption to micro-O-rings, as well as recovery of PAH and the extent of protein binding in cell culture media with and without cells for each dosing method. Bioavailability of the mixture from different dosing methods was also evaluated by characterizing in vitro cytotoxicity of the PAH mixture using EA.hy926 and HepG2 human cell lines. Of the tested dosing methods, media accommodated fraction (MAF) was determined to be the most appropriate method for cell-based studies of PAH-containing complex substances and mixtures. This conclusion is based on the observation that the highest fraction of the starting materials can be delivered using media accommodated fraction approach into cell culture media and thus enable concentration-response in vitro testing.

Although humans are continuously exposed to complex chemical mixtures in the environment, it has been extremely challenging to investigate the resulting cumulative risks and impacts. Recent studies proposed the use of “new approach methods,” in particular in vitro assays, for hazard and dose−response evaluation of mixtures. We previously found, using five human cell-based assays, that concentration addition (CA), the usual default approach to calculate cumulative risk, is mostly accurate to within an order of magnitude. Here, we extend these findings to further investigate how cell-based data can be used to quantify inter-individual variability in CA. Utilizing data from testing 42 Superfund priority chemicals separately and in 8 defined mixtures in a human cell-based population-wide in vitro model, we applied CA to predict effective concentrations for cytotoxicity for each individual, for “typical” (median) and “sensitive” (first percentile) members of the population, and for the median-to-sensitive individual ratio (defined as the toxicodynamic variability factor, TDVF). We quantified the accuracy of CA with the Loewe Additivity Index (LAI). We found that LAI varies more between different mixtures than between different individuals, and that predictions of the population median are generally more accurate than predictions for the “sensitive” individual or the TDVF. Moreover, LAI values were generally <1, indicating that the mixtures were more potent than predicted by CA. Together with our previous studies, we posit that new approach methods data from human cell-based in vitro assays, including multiple phenotypes in diverse cell types and studies in a population-wide model, can fill critical data gaps in cumulative risk assessment, but more sophisticated models of in vitro mixture additivity and bioavailability may be needed. In the meantime, because simple CA models may underestimate potency by an order of magnitude or more, either whole-mixture testing in vitro or, alternatively, more stringent benchmarks of cumulative risk indices (e.g., lower hazard index) may be needed to ensure public health protection.

The threshold of toxicological concern (TTC), i.e., the dose of a compound lacking sufficient experimental toxicity data that is unlikely to result in an adverse health effect in humans, is important for evaluating extractables and leachables (E&Ls) as it guides analytical testing and minimizes the use of animal studies. The Extractables and Leachables Safety Information Exchange (ELSIE) consortium, which consists of member companies that span biotechnology, pharmaceutical, and medical device industries, brought together subject matter expert toxicologists to derive TTC values for organic, non-mutagenic E&L substances when administered parenterally. A total of 488 E&L compounds from the ELSIE database were analyzed and parenteral point of departure ( P POD) estimates were derived for 252 compounds. The P POD estimates were adjusted to extrapolate to subacute, subchronic, and chronic durations of nonclinical exposure and the lower fifth percentiles were calculated. An additional 100-fold adjustment factor to account for nonclinical species and human variability was subsequently applied to derive the parenteral TTC values for E&Ls. The resulting parenteral TTC values are 35, 110, and 180 μg/day for human exposures of >10 years to lifetime, >1-10 years, and ≤1 year, respectively. These parenteral TTCs are expected to be conservative for E&Ls that are considered non-mutagenic per ICH M7(R1) guidelines., (© PDA, Inc. 2022.)

Human cell-based population-wide in vitro models have been proposed as a strategy to derive chemical-specific estimates of inter-individual variability; however, the utility of this approach has not yet been tested for cumulative exposures in mixtures. This study aimed to test defined mixtures and their individual components and determine whether adverse effects of the mixtures were likely to be more variable in a population than those of the individual chemicals. The in vitro model comprised 146 human lymphoblastoid cell lines from four diverse subpopulations of European and African descent. Cells were exposed, in concentration−response, to 42 chemicals from diverse classes of environmental pollutants; in addition, eight defined mixtures were prepared from these chemicals using several exposure- or hazard-based scenarios. Points of departure for cytotoxicity were derived using Bayesian concentration−response modeling and population variability was quantified in the form of a toxicodynamic variability factor (TDVF). We found that 28 chemicals and all mixtures exhibited concentration−response cytotoxicity, enabling calculation of the TDVF. The median TDVF across test substances, for both individual chemicals or defined mixtures, ranged from a default assumption (101/2) of toxicodynamic variability in human population to >10. The data also provide a proof of principle for single-variant genome-wide association mapping for toxicity of the chemicals and mixtures, although replication would be necessary due to statistical power limitations with the current sample size. This study demonstrates the feasibility of using a set of human lymphoblastoid cell lines as an in vitro model to quantify the extent of inter-individual variability in hazardous properties of both individual chemicals and mixtures. The data show that population variability of the mixtures is unlikely to exceed that of the most variable component, and that similarity in genome-wide associations among components may be used to accrue additional evidence for grouping of constituents in a mixture for cumulative assessments.

Introduction. Antibiotic resistance, particularly in cases of sepsis, has emerged as a growing global public health concern and economic burden. Current methods of blood culture and antimicrobial susceptibility testing of agents involved in sepsis can take as long as 3-5 days. It is vital to rapidly identify which antimicrobials can be used to effectively treat sepsis cases on an individual basis. Here, we present a pentaplex, real-time PCR-based assay that can quickly identify the most common beta-lactamase genes ( Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX-M); cephamycin AmpC beta-lactamases (CMY); and Oxacillinase-48 (OXA-48)) from pathogens derived directly from the blood of patients presenting with bacterial septicemia. Aim. To develop an assay which can rapidly identify the most common beta-lactamase genes in Carbapenem-resistant Enterobacteriaceae bacteria (CREs) from the United States. Hypothesis/Gap Statement. Septicemia caused by carbapenem-resistant bacteria has a death rate of 40-60 %. Rapid diagnosis of antibiotic susceptibility directly from bacteria in blood by identification of beta-lactamase genes will greatly improve survival rates. In this work, we develop an assay capable of concurrently identifying the five most common beta-lactamase and carbapenemase genes. Methodology. Primers and probes were created which can identify all subtypes of Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX); cephamycin AmpC beta-lactamase (CMY); and oxacillinase-48 (OXA-48). The assay was validated using 13 isolates containing various PCR targets from the Centre for Disease Control Antimicrobial Resistance Isolate Bank Enterobacterales Carbapenemase Diversity Panel. Blood obtained from volunteers was spiked with CREs and bacteria were separated, lysed, and subjected to analysis via the pentaplex assay. Results. This pentaplex assay successfully identified beta-lactamase genes derived from bacteria separated from blood at concentrations of 4-8 c.f.u. ml -1 . Conclusion. This assay will improve patient outcomes by supplying physicians with critical drug resistance information within 2 h of septicemia onset, allowing them to prescribe effective antimicrobials corresponding to the resistance gene(s) present in the pathogen. In addition, information supplied by this assay will lessen the inappropriate use of broad-spectrum antimicrobials and prevent the evolution of further antibiotic resistance.

Purpose: This paper reports the findings of motivational interviewing (MI) training with and without technology support on school-based health center (SBHC) providers' satisfaction with MI training, providers' self-report of behavioral counseling related to childhood overweight/obesity, and parents' perception of care after training., Design and Methods: The effects of training and technology on MI is part of a larger comparative effectiveness, cluster randomized trial. Twenty-four SBHCs in six states received virtual training on MI. Half the sites received HeartSmartKids™, a bilingual (English/Spanish), decision-support technology. The technology generated tailored patient education materials. Standard growth charts were plotted and health risks were highlighted to support MI counseling. The results of the MI training included provider satisfaction with MI training and parent assessment of the components of MI in their child's care. Providers and parents were surveyed at baseline, after training, and six months after training., Results: Providers were satisfied with training and reported improvements in counseling proficiency (p<0.0007) and psychological/emotional assessment (p=0.0004) after training. Parents in the technology group reported significant improvement in provider support for healthy eating (p=0.04)., Conclusion: Virtual training has the potential of preparing providers to use MI to address childhood obesity. Technology improved parent support for healthy eating. Future research should evaluate the impact of technology to support MI on patient outcomes., Practice Implications: Childhood obesity guidelines emphasize that MI should be used to promote healthy weight in children. Training providers on MI may help more providers incorporate obesity guidelines in their practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We investigate the effect of buffer identity, ionic strength, pH, and organic cosolvents on the rate of strain-promoted azide-alkyne cycloaddition with the widely used DIBAC cyclooctyne. The rate of reaction between DIBAC and a hydrophilic azide is highly tolerant to changes in buffer conditions but is impacted by organic cosolvents. Thus, bioconjugation reactions using DIBAC can be carried out in the buffer that is most compatible with the biomolecules being labeled, but the use of organic cosolvents should be carefully considered.

In honor of the 50th anniversary of the first nurse practitioner (NP) program in the United States, Dr. Loretta Ford offers these reflections on the progress of NPs in the past half century., (©2015 American Association of Nurse Practitioners.)

We report the 25-year follow-up on the first reported case of odontoma in the middle ear. Diagnosis of odontoma had been made on the basis of radiography films that showed a middle ear mass with multiple toothlike areas of radiopacity. No clinical intervention was recommended. At 25-year follow-up, audiometry showed progressive mixed hearing loss on the affected side and mild ipsilateral sensorineural hearing loss. Computed tomography better characterized the discrete mass, which was shaped similar to a dental crown. To avoid jeopardizing cochlear and facial nerve function, no surgical intervention was pursued, and we recommended use of a BiCROS (bilateral contralateral routing of signal) hearing aid.

Background: C-reactive protein (CRP) can provide valuable prognostic information for risk of cardiovascular events. Several automated high sensitivity CRP immunoassays are currently available for risk assessment., Methods: The analytical performance of the Synchron LX20 Pro, BN II and IMMAGE high sensitivity CRP assays were evaluated and concordance within cardiovascular risk tertiles was examined for 529 serum samples., Results: All three assays exhibited satisfactory between-run imprecision based on CVs< or =9.0% over a wide range of CRP concentrations. The LX20 Pro and BN II were linear over an extensive measuring range, whereas the IMMAGE exhibited a slight deviation from linearity producing results with a positive bias at CRP levels between 0.7 and 2.6 mg/l. Moderately hemolyzed samples interfered with the LX20 Pro and IMMAGE CRP assays, whereas moderate lipemia interfered with the BN II. Correlation studies revealed that the LX20 Pro and IMMAGE produced results 8.2% lower and 5.1% lower, respectively, compared with the BN II. There was good agreement among methods for cardiovascular risk assessment., Conclusions: All three CRP assays exhibited acceptable analytical performance for cardiovascular risk assessment. Although results by the LX20 Pro and IMMAGE were lower than the BN II, there was good agreement within each cardiovascular risk assessment tertile.

To examine the effects of technical methoxychlor (MXC) on superovulation, neonatal mice received intraperitoneal (i.p.) injections of either sesame oil, 10 micrograms of estradiol 17 beta, or 0.1, 0.5, or 1 mg of technical MXC. At 2 and 4 months, half of the mice received a superovulatory regimen of 10 IU pregnant mare's serum gonadotropin followed by 10 IU human chorionic gonadotropin. The mice were sacrificed 15 to 20 h later, the number of ovulated oocytes were counted, and the ovaries were removed for histology. In the lowest MXC dose, the ovaries appeared normal and at 2 months, ovulated the same number of oocytes as controls. Estradiol or the highest two MXC doses induced ovarian atrophy. Following gonadotropin injections, these ovaries also ovulated oocytes. However, the number of oocytes recovered from experimental mice exhibited a time- and dose-dependent decline, and by 4 months, their number was significantly reduced. Neonatal exposures to MXC reduces ovulatory rates and ovarian functions in adults.

Reflecting on 30 years of sociopolitical and professional changes in health care, the cofounder of the nurse practitioner movement compares and contrasts enabling environments, past and present, with the introduction and growth of the nurse practitioner. Differing responses of individual groups and institutions and research thrusts are reported as health care reforms offer new opportunities for the introduction of the nurse practitioner in acute care services.

Advanced OR nursing practice is emerging and the roles, responsibilities, relationships, and rewards are spread over preoperative, operative, and postoperative work units. The roles of the nurse in advanced practice are multidimensional: clinical, collegial, educative, investigatory, and administrative. Though the primary allegiance of the ANP is to nursing, she has a commitment and the skills to work collaboratively with other nurses and disciplines on the surgery team.

Patients with mycologically proven symptomatic fungal infections of the vagina were treated ina double-blind trial with either one 100-mg clotrimazole vaginal tablet daily for seven days (group I) or two tablets daily for three days (group II). Patients were evaluated at one and four weeks after therapy. The investigator's evaluation of treatment efficacy showed 85% (22/26) success in group II compared with 75% (21/28) in group I (P = 0.46). Both groups had improvement itching, discharge, and vaginal and vulval irritation. No significant (P less than 0.10) differences were seen between groups after therapy. Only three side effects were seen. It is concluded that a three-day course of two clotrimazole vaginal tablet daily is as effective and safe as the previously recommended one tablet daily for seven days, and the shorter therapy is likely to improve patient compliance.

A randomized, double-blind, multicenter trial was initiated to compare the safety and efficacy of piperacillin, cephalothin and cefoxitin in the prophylactic treatment of patients undergoing vaginal hysterectomy. The total dose of each antibiotic was 6 grams given in three equally divided doses. A satisfactory prophylactic response was obtained in 143 of 151 (95 per cent) patients treated with piperacillin, in 82 of 87 (94 per cent) patients treated with cephalothin and in 57 of 60 (95 per cent) patients treated with cefoxitin. The pooled data indicated that the piperacillin treatment group did not differ from the combined cephalosporin treatment groups with respect to prophylactic response, presence of febrile morbidity, fever index, duration of postoperative hospitalization and incidence of reported adverse experiences.

At the UCLA Vulvovaginitis Clinic, 63 patients were diagnosed as having symptomatic Candida albicans vaginal infections. In a random select manner 3-day treatment with 200-mg clotrimazole suppositories was compared with 7-day treatment using 100-mg clotrimazole suppositories. 7- and 35-day follow-up of all patients entered revealed no statistical difference between the two groups, suggesting that short-term treatment is most efficacious and can be expected to work better since patient compliance is primarily a function of duration of treatment. In 50 cases of C. albicans patients treated with miconazole or clotrimazole in a random manner, the recurrence rate was 8 or 16. All patients in the study received perianal cultures for C. albicans before treatment and 7 and 35 days after treatment. 5 of the 8 patients with recurrence had perianal positive cultures at the 7- and 35-day check suggesting this as a source of recurrence. It is suggested that patients with persistently high perianal cultures after treatment be given an oral fungicide or fungistat to lower chronic recurrent C. albicans.

Four patients with small residual ovarian carcinoma following treatment with cisplatin, doxorubicin, and cyclophosphamide have subsequently received 57 courses of ip cisplatin. Cisplatin (120-270 mg in 2 L of Ringer's lactate) was administered via Tenckhoff catheter, with a dwell time of 15-20 mins. Courses were given weekly for 12 weeks, with response documented by laparoscopy or laparotomy prior to and following the trial. With a dwell time of 20 mins, 75% +/- 5% (mean +/- SD) of platinum was recovered. With 120 mg of cisplatin and a dwell time of 20 mins, total plasma platinum peaked at 1.23 +/- 0.42 microgram/ml and by 8 hrs decreased to 0.67 +/- 0.12 microgram/ml. Filterable (non-protein-bound) platinum peaked at 0.73 +/- 0.21 microgram/ml and by 8 hrs fell to 0.03 microgram/ml. Excretion rate paralleled the filterable plasma curve, peaking at 40 mins; 30% +/- 7% of absorbed drug was recovered in urine within 24 hrs. Renal clearance of filterable platinum was 106 +/- 20 ml/min. Creatinine clearance was 76 +/- 7 ml/min. Three responses, one complete and two partial, were noted. Zero to two episodes of vomiting occurred in each course. One patient had a creatinine clearance decrease to 40 ml/min, one had two episodes of thrombocytopenia, and one had mild abdominal pain with a cisplatin dose of greater than or equal to 210 mg. No neurotoxicity, catheter infection, or peritonitis was encountered.

Cisplatin at a dose of 3 mg/kg was administered to dogs either iv or ip. Cisplatin concentrations in serum, urine, and tissues were measured with a radioisotope tracer method employing 195mPt cisplatin. Systemic toxicity was monitored by serial BUN, creatinine, and wbc and platelet counts. The mode of administration did not affect systemic toxicity since the changes in renal and bone marrow functions were identical in the two groups. Serum cisplatin levels following iv administration peaked at 13.5 micrograms/ml at 5 minutes and were biphasic with rapid initial decline and a prolonged elimination phase. In contrast, levels following ip administration increased rapidly to 1.5 micrograms/ml at 4 hours and then decreased with the iv levels. The amount of drug recovered in the urine was similar regardless of method of administration, with approximately 50% of the injected dose excreted by Day 4. The drug levels within the tissues on Days 4 and 8 were similar, with the exception of the tissues lining the peritoneal cavity. On Day 4 the tissues lining the peritoneal cavity had 2.5-8 times higher levels of drug after ip administration, and this difference was statistically significant (P less than 0.01). Local toxic effects encountered with ip administration consisted of bloody ascites on Day 4 (four of none dogs) and filmy adhesions on Day 8 (one of four dogs). It is concluded that ip cisplatin chemotherapy may increase the therapeutic index for small tumors which are confined to the peritoneal cavity.

Cytoplasmic receptors for 17 beta-estradiol (ER) and progesterone (PR) were measured in uterine cervical, vaginal, and vulvar carcinomas by the dextran-coated charcoal (DCC) technique. Tissues from 30 patients with cervical carcinoma were examined. Thirteen percent (2 of 16) of well-differentiated squamous carcinomas had positive ER, and 19% (3 of 19) had positive PR. None of the three patients with moderately well-differentiated disease have positive ER or PR, while two of five patients with poorly differentiated lesions contained measurable ER and PR. In contrast, all four of the well-differentiated adenocarcinomas of the cervix had detectable ER, and three of four for PR. Neither of the two patients with poorly differentiated adenocarcinoma had either ER or PR. None of the five vulvar and seven vaginal epidermoid carcinomas studied had ER or PR activity. Hormonal therapies may be useful in the treatment of adenocarcinoma of the cervix.