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Pentosan polysulfate sodium (PPS) is the active ingredient in ELMIRON®, a drug approved for the relief of bladder pain associated with interstitial cystitis. The study objective was to characterize the pharmacokinetic and metabolic profiles of PPS following oral dosing of [ 3 H]PPS. As specific assays for PPS do not exist, metabolic profiling was accomplished through multiple fraction collections and radiochromatographic techniques. Two groups of eight healthy female subjects sequentially received a single oral dose of 200   µ Ci [ 3 H]PPS supplemented with 300  mg unlabelled PPS or 300  µCi [ 3 H]PPS supplemented with 450  mg unlabelled PPS. Most of the administered dose (84%) was excreted in faeces as intact PPS, and a smaller percentage (6%) was excreted in urine. In summary, orally administered PPS was very poorly absorbed, with the majority of the drug being excreted in faeces as intact PPS and in urine as low molecular weight and desulfated PPS. [ABSTRACT FROM AUTHOR]

Pethoxamid (PXA) is a chloroacetamide herbicide that works by inhibiting the germination of target weeds in crops. PXA is not a genotoxic agent, however, in a two-year chronic toxicity study, incidence of thyroid follicular cell hyperplasia was observed in male rats treated at a high dose. Many non-mutagenic chemicals, including agrochemicals are known to produce thyroid hyperplasia in rodents through a hepatic metabolizing enzyme induction mode of action (MoA). In this study, the effects of oral gavage PXA treatment at 300 mg/kg for 7 days on the disposition of intravenously (iv) administered radio-labeled thyroxine ([ 125 I]-T4) was assessed in bile-duct cannulated (BDC) rats. Another group of animals were treated with phenobarbital (PB, 100 mg/kg), a known enzyme inducer, serving as a positive control. The results showed significant increase (p < 0.01) in the mean liver weights in the PB and PXA-treated groups relative to the control group. The serum total T4 radioactivity C max and AUC 0 - 4 values for PB and PXA-treated groups were lower than for the control group, suggesting increased clearance from serum. The mean percentages of administered radioactivity excreted in bile were 7.96 ± 0.38%, 16.13 ± 5.46%, and 11.99 ± 2.80% for the control, PB and PXA groups, respectively, indicating increased clearance via the bile in the treated animals. These data indicate that PXA can perturb the thyroid hormone homeostasis in rats by increasing T4 elimination in bile, possibly through enzyme induction mechanism similar to PB. In contrast to humans, the lack of high affinity thyroid binding globulin (TBG) in rats perhaps results in enhanced metabolism of T4 by uridine diphosphate glucuronosyl transferase (UGT). Since this liver enzyme induction MoA for thyroid hyperplasia by PB is known to be rodent specific, PXA effects on thyroid can also be considered not relevant to humans. The data from this study also suggest that incorporating a BDC rat model to determine thyroid hormone disposition using [ 125 I]-T4 is valuable in a thyroid mode of action analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gopinath Nallani (GN) reports a relationship with FMC Corporation that includes employment. Appavu Chandrasekaran (AC) reports a relationship with FMC Corporation that includes employment at the time of initial submission of the manuscript in Jan 2024. AC has since retired from FMC and is now an employee of Frontage Labs. Karin Bentley (KB) reports a relationship with FMC Corporation that includes employment. Robert McClanahan (RM) reports a relationship with Frontage Labs that includes employment. RM was the study director during the study conduct. FMC Corporation sponsored and contracted out the study to Frontage Labs, Concord, OH. There are no other 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.)

Role transition can be a struggle for new or seasoned nurses moving into the specialty of school. School nursing, a specialized field that entails a scope of practice and competencies very different from other settings, is not taught in many primary nursing education programs. New nurses may find themselves unprepared for their role without a proper orientation, causing them to feel anxious and not ready to care for students properly, leading to attrition. This article describes the barriers and facilitators to smooth role transition and provides evidence-based orientation strategies for new school nurses.

The demand for schools to provide complex health-care services for students with chronic conditions has induced districts to hire licensed vocational nurses (LVNs). Questions remain about how overlapping responsibilities and skills of nursing staff works to facilitate care. The purpose of this mixed-methods descriptive study was to examine the use of LVNs to identify factors related to the supports and impediments to school nurse (SN) practice. The sample consisted of members of the California School Nurse Organization, and methodologies consisted of an online survey and one-on-one interviews. LVNs perform duties within their scope of practice, allowing SNs time for activities related to the Framework for 21st Century School Nursing Practice TM , confirming appropriate use, and alignment with National Association of School Nurses guidance on the utilization of LVNs. Identified areas of concern included role definition and orientation and supervision of the LVN. Insights into best practices for the effective addition of the LVN to the team are provided.

Most children receiving cancer treatment require a central venous catheter (CVC), putting them at risk for central line-associated bloodstream infections (CLABSI). As patients are discharged home with a CVC in place, caregivers are expected to maintain the CVC following an in-hospital education session before their first discharge home. Following a review of the literature, the education process was modified to improve the quality of education for caregivers. While the existing step-by-step handbook was reviewed and deemed aligned with best practices, other materials were added for this project: a caregiver skills competency checklist, a handout reviewing oral care and hygiene in the home, and a guide for nurses on what materials to provide families at the time of diagnosis. Additionally, caregivers were required to receive two additional CVC care reinforcement sessions during subsequent admissions to the inpatient units, which involved redemonstrations of skills using the competency checklist. Home-acquired CLABSI in pre- and postintervention groups were compared, and compliance of reinforcement education was measured. Though no statistical significance was found, the odds of experiencing a CLABSI were found to be higher in the preintervention group for mucosal-barrier injury (odds ratio = 2.23; 95% confidence interval [0.43, 22.10]) and laboratory-confirmed bloodstream infections (odds ratio = 4.53; 95% confidence interval [0.59, 203.71]). The clinical significance of reducing home-acquired CLABSI has a positive impact on patient outcomes by decreasing morbidity and mortality, inpatient lengths of stay, and overall health care costs.

School attendance is a predictor of academic achievement. Chronic absenteeism, defined as missing 10% or more school days affects 14% of all students nationwide. District attendance processes, policies, and data were analyzed in a demographically diverse southern California high school. A review of the attendance history of 117 ninth and tenth graders, who missed at least 10% of days in school, showed that 66% of the absences were due to illness. Prior to the project, these students were not referred for nursing intervention. Results of this quality improvement project supported the adoption of a specific code for absences due to illness. A district procedure for illness chronic absence was adopted to allow early nursing intervention for students with chronic absences prior to the development of illness-related academic underperformance. This project demonstrates nursing roles in the quality improvement and care coordination aspects of the NASN's Framework for 21st Century School Nursing Practice™.

Adolescent depression is a silent epidemic in this country. Untreated depression has detrimental effects on physical health, psychosocial well-being, and academic productivity. It is important for school nurses to be able to recognize depression and refer students promptly for treatment. This article and its associated learning module will provide school nurses with updated information on adolescent depression, discuss barriers in depression screening, use of the PHQ-9 (Patient Health Questionaire-9 Item) as an evidence-based depression screening tool in the educational setting, and the important role of school nurses in depression screening. It is anticipated that by increasing awareness and knowledge about adolescent depression and providing training in the use of an evidence-based screening tool, school nurses will have greater confidence in identifying and referring students in need. (A free online depression screening education module developed by the lead author is available at https://sites.google.com/view/depressionscreeningtraining .).

Nurses are increasingly being called upon to lead changes within health care. How do nurses and, in particular, school nurses become leaders? School nurses lead daily in their work but often do not recognize themselves as leaders. The "Five C's of Leadership"-character, commitment, connectedness, compassion, and confidence-identified by Kowalski and Yoder-Wise are foundational to the development of leadership and are particularly relevant to school nurses and their role. Two additional attributes found in the literature-courage and capacity-also undergird school nursing practice. In this article, we describe how school nurses already embody these leadership qualities. Each leadership attribute is reviewed in light of the literature, followed by specific examples to demonstrate how school nurses provide leadership. Through these illustrations, school nurses can recognize and embrace their present leadership abilities. In addition, by using the "Seven C's" of leadership, school nurses can enhance their inherent leadership abilities., (© 2015 The Author(s).)

Health care for students with chronic needs can be complex and specialized, resulting in fragmentation, duplication, and inefficiencies. Students who miss school due to chronic conditions lose valuable educational exposure that contributes to academic success. As health-related disabilities increase in prevalence so does the need for the coordination of care within the school and between the school and service providing agencies. This integrative literature review provides a synthesis of published evidence identifying and describing the core concepts associated with the role of school nurses in providing care coordination/case management to students with complex needs. Six core essentials of nurse-provided care coordination were identified: collaboration, communication, care planning and the nursing process, continuous coordination, clinical expertise, and complementary components. Recommendations for improving care coordination were elucidated in the review. Analysis of the literature can help assure application of best practice methods for the coordination of care for students in the school setting., (© The Author(s) 2014.)

We equipped an insole with a force sensor that can detect in real time when a foot over pronates. When such behavior is detected, we warn the user so they can correct their posture by using their own muscles. The effectiveness of this novel way to correct over pronation posture is evaluated over a two-week period. The use of vibrotactile feedback reduces over pronation by 30% to 50% during the first week. The natural benefits of the proposed method vs. use of passive orthotics are also presented.

Since 2006, Geomyces destructans, the causative agent of white nose syndrome (WNS), has killed over 5.7 million bats in North America. The current hypothesis suggests that this novel fungus is an invasive species from Europe, but little is known about the diversity within the genus Geomyces and its distribution on bats in the United States. We documented the psychrophilic and psychrotolerant fungal flora of hibernating bats prior to the arrival of WNS using culture-based techniques. A total of 149 cultures, which were obtained from 30 bats in five bat hibernacula located in four caves and one mine, were sequenced for the entire internal transcribed spacer (ITS) nuclear ribosomal DNA (nrDNA) region. Approximately 53 operational taxonomic units (OTUs) at 97% similarity were recovered from bat wings, with the community dominated by fungi within the genera Cladosporium, Fusarium, Geomyces, Mortierella, Penicillium, and Trichosporon. Eleven Geomyces isolates were obtained and placed in at least seven distinct Geomyces clades based on maximum-likelihood phylogenetic analyses. Temperature experiments revealed that all Geomyces strains isolated are psychrotolerant, unlike G. destructans, which is a true psychrophile. Our results confirm that a large diversity of fungi, including several Geomyces isolates, occurs on bats prior to the arrival of WNS. Most of these isolates were obtained from damaged wings. Additional studies need to be conducted to determine potential ecological roles of these abundant Geomyces strains isolated from bats.

The diagnosis of human cases of tularemia often relies upon the demonstration of an antibody response to Francisella tularensis or the direct culturing of the bacteria from the patient. Antibody response is not detectable until 2 weeks or more after infection, and culturing requires special media and suspicion of tularemia. In addition, handling live Francisella poses a risk to laboratory personnel due to the highly infectious nature of this pathogen. In an effort to develop a rapid diagnostic assay for tularemia, we investigated the use of TaqMan 5' hydrolysis fluorogenic PCR to detect the organism in tissues of infected mice. Mice were infected to produce respiratory tularemia. The fopA and tul4 genes of F. tularensis were amplified from infected spleen, lung, liver, and kidney tissues sampled over a 5-day period. The samples were analyzed using the laboratory-based Applied Biosystems International 7900 and the Smiths Detection-Edgewood BioSeeq, a hand-held portable fluorescence thermocycler designed for use in the field. A comparison of culturing and PCR for detection of bacteria in infected tissues shows that culturing was more sensitive than PCR. However, the results for culture take 72 h, whereas PCR results were available within 4 h. PCR was able to detect infection in all the tissues tested. Lung tissue showed the earliest response at 2 days when tested with the ABI 7900 and in 3 days when tested with the BioSeeq. The results were in agreement between the ABI 7900 and the BioSeeq when presented with the same sample. Template preparation may account for the loss of sensitivity compared to culturing techniques. The hand-held BioSeeq thermocycler shows promise as an expedient means of forward diagnosis of infection in the field.

Analogs of tris(2,3-dibromopropyl)phosphate (Tris-BP) either labeled at specific positions with carbon-14 and phosphorus-32 or dual-labeled with both deuterium and tritium were administered to male Wistar rats at a nephrotoxic dose of 360 mumol/kg. The covalent binding of Tris-BP metabolites to hepatic, renal, and testicular proteins was determined after 9 and 24 hr, and plasma concentrations of bis(2,3-dibromopropyl)-phosphate (Bis-BP) formed metabolically from Tris-BP were measured at intervals throughout the initial 9-hr postdosing period. The covalent binding of 14C-Tris-BP metabolites in the kidney (2495 +/- 404 pmol/mg protein) was greater than that in the liver (476 +/- 123 pmol/mg protein) or testes (94 +/- 11 pmol/mg protein); the extent of renal covalent protein binding of Tris-BP metabolites was decreased by 82 and 84% when deuterium was substituted at carbon-2 and carbon-3, respectively. Substitution of Tris-BP with deuterium at carbon-2 or carbon-3 also decreased the mean area under the curve for Bis-BP plasma concentration by 48 and 57%, respectively. The mechanism of Tris-BP-induced renal and hepatic DNA damage was evaluated in Wistar rats by an automated alkaline elution procedure after the administration of analogs of Tris-BP or Bis-BP labeled at specific positions with deuterium. Renal DNA damage was decreased when Tris-BP was substituted with deuterium at either carbon-2 or carbon-3; the magnitude of the change correlated with both a decrease in the area under the Bis-BP plasma curve and a decrease in renal covalent binding of Tris-BP metabolites for each of the deuterated analogs. In marked contrast, analogs of Bis-BP labeled with deuterium at carbon-2 or carbon-3 did not show a decrease in the severity of renal DNA damage compared to unlabeled Bis-BP. On the basis of these observations a metabolic scheme for hepatic P-450-mediated oxidation at either carbon-2 or carbon-3 of Tris-BP affording Bis-BP by two alternate pathways that are susceptible to primary deuterium kinetic isotope effects is proposed. The Tris-BP metabolite, Bis-BP, is subsequently metabolized to reactive intermediates that cause DNA damage and bind to kidney proteins in a mechanism independent of cytochrome P-450.

Analogs of tris(2,3-dibromopropyl)phosphate (Tris-BP) either labeled at specific positions with carbon-14, phosphorus-32, or oxygen-18 or dual-labeled with both deuterium and tritium were used as metabolic probes to study the chemical and metabolic events in the bioactivation of Tris-BP to chemically reactive metabolites in liver microsomal preparations. Oxidation at the terminal (C-3) carbon atom of the propyl groups of Tris-BP yielded the direct-acting mutagen 2-bromoacrolein as the major metabolite that binds to DNA. Although this reactive metabolite also appears to bind to microsomal protein, the rate of binding of radiolabeled Tris-BP to protein is 15-20x greater than binding to DNA, and some metabolites that retain the phosphate group are bound. Studies with deuterated analogs of Tris-BP implicate oxidation at C-2 of the propyl group as a major pathway that leads to protein binding which is enhanced by phenobarbital pretreatment of rats. Moreover, investigations with 18O-Tris-BP and H2(18)O show that Bis-BP that is formed from oxidation of Tris-BP incorporates one atom of oxygen from water. Deuterium isotope studies suggest that most of the Bis-BP arises from initial oxidation at C-2. Taken together these studies indicate that P-450 oxidation of Tris-BP at C-2 of the propyl group yields a reactive alpha-bromoketone metabolite of Tris-BP that can either alkylate proteins directly or be hydrolyzed to Bis-BP and an alpha-bromo-alpha'-hydroxyketone that can alkylate microsomal proteins.