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The goal of this article is to define the role and responsibilities of the oral anticancer medication nurse navigator. This article combines findings from a review of scientific literature including research studies, quality improvement projects, case studies, standards, and guidelines combined with the experience and professional insights of the authors in the role creation and function of the oral anticancer medication nurse navigator. The role of the oral anticancer medication nurse navigator includes coordination of patient care, pre-treatment assessment of barriers to adherence, patient and caregiver education, planned follow-up and coaching, and symptom management. Professionally, the role includes the development of interdisciplinary workflows, coordination of care with internal and external stakeholders, clinical staff education, the application of technology, and advocacy. The oral anticancer medication nurse navigator uses the nursing process to coordinate care of the individual taking these medications. The role optimizes patient outcomes and benefits the healthcare organization through reduced healthcare costs and the ability to meet accreditation needs. The role of the oral anticancer medication nurse navigator provides value to patients taking oral anticancer medications and to the healthcare team. [ABSTRACT FROM AUTHOR]

Randomly barcoded transposon mutant libraries are powerful tools for studying gene function and organization, assessing gene essentiality and pathways, discovering potential therapeutic targets, and understanding the physiology of gut bacteria and their interactions with the host. However, construction of high-quality libraries with uniform representation can be challenging. In this review, we survey various strategies for barcoded library construction, including transposition systems, methods of transposon delivery, optimal library size, and transconjugant selection schemes. We discuss the advantages and limitations of each approach, as well as factors to consider when selecting a strategy. In addition, we highlight experimental and computational advances in arraying condensed libraries from mutant pools. We focus on examples of successful library construction in gut bacteria and their application to gene function studies and drug discovery. Given the need for understanding gene function and organization in gut bacteria, we provide a comprehensive guide for researchers to construct randomly barcoded transposon mutant libraries. To address the need for understanding gene function and pathways in gut bacteria, Tripathi et al. provide a comprehensive guide for constructing randomly barcoded transposon mutant libraries. Strategies for library construction, emphasizing transposition systems, delivery methods, and library size, plus advances and practices for generating arrayed mutant collections are reviewed. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cells (CAR-T cells) are increasingly used to treat haematological malignancies. Strategies for preventing infections in CAR-T-treated patients rely on expert opinions and consensus guidelines. This scoping review aimed to identify risk factors for infections in CAR-T-treated patients with haematological malignancies. A literature search utilized MEDLINE, EMBASE and Cochrane to identify relevant studies from conception until 30 September 2022. Trials and observational studies were eligible. Studies required ≥10 patients treated for haematological malignancy to report infection events (as defined by the study), and either (a) a descriptive, univariate or multivariate analysis of the relationship between infections event and a risk factors for infections, or (b) diagnostic performance of a biochemical/immunological marker in CAR-T-treated patients with infection. A scoping review was conducted in accordance with PRISMA guidelines. Data sources: A literature search utilised MEDLINE, EMBASE and Cochrane to identify relevant studies from conception until September 30, 2022. Eligibility/Participants/Intervention: Trials and observational studies were eligible. Studies required ≥ 10 patients treated for haematological malignancy, to report infection events (as defined by the study), and either A) a descriptive, univariate or multivariate analysis of the relationship between infections event and a risk-factors for infections, or B) diagnostic performance of a biochemical/immunological marker in CAR-T treated patients with infection. Bias assessment was undertaken according to Joanna Brigg's Institute criteria for observational studies. Data were synthesized descriptively because of the heterogeneity of reporting. A total of 1522 patients across 15 studies were identified. All-cause infections across haematological malignancies were associated with lines of prior therapy, steroid administration, immune-effector cell-associated neurotoxicity and treatment-emergent neutropenia. Procalcitonin, C-reactive protein and cytokine profiles did not reliably predict infections. Predictors of viral, bacterial and fungal infections were poorly canvassed. Meta-analysis of the current literature is not possible because of significant heterogeneity in definitions of infections and risk factors, and small, underpowered cohort studies. Radical revision of how we approach reporting infections for novel therapies is required to promptly identify infection signals and associated risks in patients receiving novel therapies. Prior therapies, neutropenia, steroid administration and immune-effector cell-associated neurotoxicity remain the most associated with infections in CAR-T-treated patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Study Objective To determine the factors that allow for a safe outpatient robotic-assisted minimally invasive gynecologic oncology surgery procedure. Design Retrospective chart review (Canadian Task Force classification II-1). Setting University hospital. Patients All patients (140) undergoing robotic-assisted minimally invasive surgery with the gynecologic oncology service from January 1, 2013, to December 31, 2013. Interventions Risk factors for unsuccessful discharge within 23 hours of surgery and same-day discharge were assessed using logistic regression models. Measurements and Main Results All patients were initially scheduled for same-day discharge. The outpatient surgery group was defined by discharge within 23 hours of the surgery end time, and a same-day surgery subgroup was defined by discharge before midnight on the day of surgery. One hundred fifteen (82.1%) were successfully discharged within 23 hours of surgery, and 90 (64.3%) were discharged the same day. The median hospital stay was 5.3 hours (range, 1–48 hours). Unsuccessful discharge within 23 hours was associated with a preoperative diagnosis of lung disease and intraoperative complications; unsuccessful same-day discharge was associated with older age and later surgery end time. Only 2 patients (1.4%) were readmitted to the hospital within 30 days of surgery. Conclusions Outpatient robotic-assisted minimally invasive surgery is safe and feasible for most gynecologic oncology patients and appears to have a low readmission rate. Older age, preoperative lung disease, and later surgical end time were risk factors for prolonged hospital stay. These patients may benefit from preoperative measures to facilitate earlier discharge. [ABSTRACT FROM AUTHOR]

A self-report questionnaire was used to assess the level of knowledge among a convenience sample of 34 elementary school teachers in a rural school district in Illinois. The questionnaire addressed general asthma knowledge and management, including signs and symptoms, triggers, and treatment. The results suggest a knowledge deficit among this sample of elementary school teachers; the average score was 75%. Teachers with an increased exposure/experience with asthma scored significantly higher than did those with limited exposure. Implications of these findings for schools in rural areas are discussed. [Copyright &y& Elsevier]

Abstract: The environmentally prevalent arsenate (AsV) undergoes reduction in the body to the much more toxic arsenite (AsIII). Phosphorolytic enzymes and ATP synthase can promote the reduction AsV by converting it into arsenylated products in which the pentavalent arsenic is more reducible by glutathione (GSH) to AsIII than in inorganic AsV. Glutathione synthetase (GS) can catalyze the arsenolysis of GSH (γ-Glu-Cys-Gly) yielding two arsenylated products, i.e. γ-Glu-Cys-arsenate and ADP-arsenate. Thus, GS may also promote the reduction of AsV by GSH. This hypothesis was tested with human recombinant GS, a Mg2+ dependent enzyme. GS markedly increased AsIII formation when incubated with AsV, GSH, Mg2+ and ADP, but not when GSH, Mg2+ or ADP were separately omitted. Phosphate, a substrate competitive with AsV in the arsenolysis of GSH, as well as the products of GSH arsenolysis or their analogs, e.g. glycine and γ-Glu-aminobutyrate, decreased AsV reduction. Replacement of ADP with ATP or an analog that cannot be phosphorylated or arsenylated abolished AsV reduction, indicating that GS-supported AsV reduction requires formation of ADP-arsenate. In the presence of ADP, however, ATP (but not its metabolically inert analog) tripled AsV reduction because ATP permits GS to remove the arsenolysis inhibitory glycine and γ-Glu-Cys by converting them into GSH. GS failed to promote AsV reduction when GSH was replaced with ophthalmic acid, a GSH analog substrate of GS containing no SH group (although ophthalmic acid did undergo GS-catalyzed arsenolysis), indicating that the SH group of GSH is important for AsV reduction. Our findings support the conclusion that GS promotes reduction of AsV by catalyzing the arsenolysis of GSH, thus producing ADP-arsenate, which upon being released from the enzyme is readily reduced by GSH to AsIII. [Copyright &y& Elsevier]

Nursing turnover in health care organizations is a considerable problem that needs to be reframed within the context of "nurse retention" and "job embeddedness" (JE). A construct from the business literature, JE has been associated with "retention" or "antiwithdrawal." Conversely, turnover encompasses the process of quitting. This distinction is significant. JE represents a mediating construct between various "on-the-job" (organizational) factors, "off- the-job" (community) factors, and employee retention. This article presents an overview of JE including the dimensions, the related concepts of turnover and retention, and associated research. JE may be used to develop specific nurse-retention strategies following careful organizational and community assessment. With the current and looming nursing shortage, perhaps it is time for health care institutions to consider the adaptation of JE tenets. [ABSTRACT FROM AUTHOR]

Background: To perform a colonoscopy, the endoscopist maneuvers the colonoscope through a series of loops by applying force to the insertion tube. Colonoscopy insertion techniques are operator dependent but have never been comprehensively quantified. Objective: To determine whether the Colonoscopy Force Monitor (CFM), a device that continually measures force applied to the insertion tube, can identify different force application patterns among experienced endoscopists. Design: Observational study of 6 experienced endoscopists performing routine diagnostic and therapeutic colonoscopy in 30 patients. Setting: Outpatient ambulatory endoscopy center. Patients: Adult male and female patients between 30 and 75 years of age undergoing routine colonoscopy. Interventions: CFM monitoring of force applied to the colonoscope insertion tube during colonoscopy. Main Outcome Measurements: Maximum and mean linear and torque force, time derivative of force, combined linear and torque vector force, and total manipulation time. Results: The CFM demonstrates differences among endoscopists for maximum and average push/pull and mean torque forces, time derivatives of force, combined push/torque force vector, and total manipulation time. Endoscopists could be grouped by force application patterns. Limitations: Only experienced endoscopists using conscious sedation in the patients were studied. Sample size was 30 patients. Conclusions: This study demonstrates that CFM allows continuous force monitoring, characterization, and display of similarities and differences in endoscopic technique. CFM has the potential to facilitate training by enabling trainees to assess, compare, and quantify their techniques and progress. [Copyright &y& Elsevier]

Abstract: Scholarly productivity is a key component of faculty evaluation at many universities. In fact, under current accreditation standards promulgated by the AACSB, faculty members must remain academically qualified in research. Here we provide evidence regarding faculty research productivity. The determinants of faculty productivity are estimated with data spanning a 20 year period for 487 accounting doctoral graduates during the years of 1980–82. Sample statistics reveal that a relatively small portion of researchers produce over half of the sample''s articles. Also, our regression results suggest that top-tier institutions of first hire, larger department size of initial hire, and the experience within academic ranks are all positive determinants of scholarly productivity. Conversely, research output is reduced with increased time spent teaching and accepting an initial hire at a public rather than a private institution. [Copyright &y& Elsevier]

There is increasing evidence for the efficacy of certain forms of selenium as cancer-chemopreventive compounds. Methylselenol has been hypothesized to be a critical selenium metabolite for anticancer activity in vivo. To determine whether tumor cell migration, invasion, and cell cycle characteristics are inhibited by methylselenol, we exposed HT1080 cells to methylselenol. Methylselenol was generated with seleno-L-methionine (a substrate for methioninase). Submicromolar methylselenol exposure led to an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, indicating slower cell growth. Furthermore, methylselenol inhibited the migration and invasion rate of the tumor cells by up to 53 and 76%, respectively, when compared with the control tumor cells. Although all cells had increased matrix metalloproteinase (MMP) enzyme activities of pro-MMP-2 and pro-MMP-9, the active form of MMP-2 was decreased in HT1080 cells cultured with methylselenol. In addition, methylselenol increased the protein levels of antimetastasic tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2. Collectively, these results demonstrate that submicromolar concentrations of methylselenol increase both prometastasis MMP-2 and MMP-9 and antimetaslasis TIMP-1 and TIMP-2 expression. The apparent net effect of these changes is the inhibition of pro-MMP-2 activation and carcinogenic potential or activity. [ABSTRACT FROM AUTHOR]

Over the past decade, the courts have been called upon to apply the provisions of the Americans With Disabilities Act and Section 504 of the Rehabilitation Act in several cases with implications for programs of nursing education. Courts have restricted who may be considered a qualified individual with disabilities. They have clarified the relative obligations of both students and educators in determining accommodations. Courts have been especially deferential to educational programs preparing health care professionals when program standards and pedagogical requirements are clearly articulated. However, accessibility and compliance with recommendations for accommodations are required at all sites where students are educated. Less clear are judicial interpretations related to making technology accessible and to the disclosure by programs of information about students'' disabilities during licensing. These findings lead to several conclusions. First is the need for development of profession-wide standards of competencies and skills for nurses. Second is the need for dialogue about the potential for disability discrimination between nursing educators and state licensing bodies. Last is that faculty and administrators can proceed with some degree of confidence in protecting program practices that are based on sound pedagogical reasoning. [Copyright &y& Elsevier]

Butyrate, a normal constituent of the colonic luminal contents, is produced by the bacterial fermentation of dietary fibers and resistant starches. It has been hypothesized that butyrate may inhibit the invasion of tumor cells. The purpose of the present study was to investigate the effects of butyrate treatment on the growth, migration, and invasion characteristics of tumor HT1080 cells. HT1080 cells cultured in the presence of 0.5 and 1 mmol/L butyrate for 14 d exhibited an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, thus showing slower cell growth. Interestingly, 0.5 and 1 mmol/L butyrate inhibited the migration and invasion rate of the tumor cells compared with the untreated (control) cells. The protein and mRNA levels of the tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2 were significantly increased in HT1080 cells cultured with 0.5 and 1 mmol/L butyrate. Enzymatic activities and the mRNA level of the latent forms of matrix metalloproteinase (MMP), pro-MMP-2 and pro-MMP-9, were also increased in HT1080 cells cultured with 0.5 and 1 mmol/L butyrate. In contrast, the active form of MMP-2 was detectable by zymographic analysis in control but not butyrate-conditioned media. Collectively, these results demonstrate that prolonged and Iow-dose butyrate treatment increases both prometastasis MMP-2, -9 and antimetastasis TIMP-1, -2 expression, and the net effect of these increases is the inhibition of pro-MMP-2 activation and of tumor cell migration/invasion potential. [ABSTRACT FROM AUTHOR]

The sphingolipid, ceramide, is a natural dietary constituent and a potent mediator of apoptosis. If left undegraded, it may induce apoptosis and cause disruption of cellular integrity. A potential mechanism to prevent ceramide-induced apoptosis in various organs may involve ceramidases that facilitate the degradation of ceramide. In this study, we first isolated and characterized the murine neutral ceramidase (N-CDase) gene, mapped its chromosomal location and determined its developmental and organ-specific expression. Then we used cultured mesangial cells as our in vitro model and mouse gastrointestinal (GI) tract as the in vivo model to determine the effects of an inhibitor of N-CDase, d-erythro-MAPP, to delineate whether N-CDase plays a role in preventing ceramide-induced apoptosis. Our results show that: (i) the structure of the murine neutral ceramidase gene is virtually identical to that of the human gene; (ii) it is localized on chromosome 19 at bands C2–C3 that is syntenic to human chromosome 10q24–26; (iii) N-CDase expression is developmentally regulated and it is expressed at high levels in cultured mesangial cells and in specific regions of the mouse small intestine; (iv) inhibition of N-CDase by d-erythro-MAPP leads to increased ceramide levels and consequent apoptosis in cultured mesangial cells; (v) mice treated with d-erythro-MAPP alone also caused apoptosis in the small intestine; and (vi) mice treated with d-erythro-MAPP prior to feeding C2 ceramide manifest markedly elevated levels of apoptosis in the GI tract raising the possibility that neutral ceramidase plays a detoxifying role against inadvertent stimulation of ceramide-induced apoptosis in organs that come in contact with this sphingolipid. We propose that N-CDase is an essential component of an innate detoxifying mechanism to prevent ceramide-induced apoptosis. [Copyright &y& Elsevier]

Copper uptake was enhanced and copper transport was reduced in Caco-2 cells cultured in media containing high concentrations of zinc. Here we show that physiologic zinc concentrations also affect copper movement into and out of Caco-2 cells. Cells were seeded onto Falcon membranes with high pore density and maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, nonessential amino acids, glucose and glutamine. In one experiment, the cells were exposed to media containing either 5 or 25 micromol zinc/L from d 14 to 21 after seeding. Then, copper uptake and transport, in both apical and basolateral directions, were measured by using 64Cu. Cells exposed to 25 micromol zinc/L had a 25% higher (P < 0.05) uptake of 64Cu from the apical side than those exposed to 5 micromol zinc/L. There was no effect of zinc on 64Cu uptake from the basolateral side, even though the amount of label taken up was as much as threefold higher (P > 0.05) than from the apical side. Transport of 64Cu across the cell layer in both directions was 50% less (P < 0.05) in cells exposed to 25 micromol zinc/L vs. 5 micromol zinc/L. In another experiment, zinc-exposed cells were labeled with 64Cu and efflux of the label to the apical and basolateral sides was measured over time. The rate of efflux to the apical side was linear and not affected by zinc. However, there was a 37% reduction (P < 0.05) in 64Cu efflux to the basolateral side by the higher zinc concentration. Curve-fit analysis showed that the basolateral efflux was made up of an exponential and a linear component. Cellular zinc concentrations were proportional to the zinc concentrations in the media. Although the data suggest that high media zinc inhibited the copper efflux transporter and enhanced the influx transporter, copper did not accumulate in the cell. [ABSTRACT FROM AUTHOR]

Reports on a study which determined the effects of high zinc concentrations in the culture medium on copper uptake and transport in differentiated human colon adenocarcinoma cells. Cell culture; Cell morphology and maturation; Cell monolayer integrity; Metallothionein determinations; Zinc and copper determination in the medium and Caco-2 cells.

[Display omitted] • C-H activation by "methane proteases" depends on metal & ligand acid-base properties. • Change of metal complex's coordination sphere reduces methane activation barriers. • Fluorination of histidine-aspartate base impacts enthalpic barriers by ±4½ kcal/mol. • Metal ion identity and ligand substituents have most and least impact upon barriers. Metal-based bifunctional methane activators are modeled utilizing density functional theory. The impact upon activation barriers of the metal among the late 3d metal MII ions (Co – Zn) is quite pronounced, ca. 7 kcal/mol. Alteration of the metal's coordination environment without changing the supporting ligand types (e.g. , comparing cis and trans coordination isomers) has a computed impact on methane activation barriers of ± 1 kcal/mol. One significant result involves the varying impact of fluorination of the imidazole, which serves as a simple mimic of a histidine side chain. Sequentially fluorinating the 3C–H bonds of imidazole produces a range in the calculated ΔH‡ of 4½ kcal/mol, an effect greater than any other modeled herein apart from the impact of changing the central metal ion of the active site. As such, the present research yields insight into possible avenues for bio-inspired methane activators. [ABSTRACT FROM AUTHOR]

Venetoclax, the BCL2 inhibitor, is highly effective for the treatment of chronic lymphocytic leukaemia (CLL), a disease marked by BCL2 overexpression. The highly encouraging results from clinical trials has led to its approval in many jurisdictions, including recent listing in Australia on the Pharmaceutical Benefits Scheme (PBS). In spite of its efficacy, many treated patients will eventually experience disease progression after several years. At the current time, we do not fully understand why resistance emerges. Our research group is well placed to address this question as we have access to one of the largest cohorts of venetoclax-treated patients, and access to serially collected samples such as prior to venetoclax therapy and at progression. Our preliminary data indicates that amongst patients who have progressive CLL while on venetoclax, multiple mechanisms drive resistance even within a patient. While the recently discovered BCL2 G101V mutation accounted significantly for the resistance, we found evidence for co-existing adverse genetic changes (e.g. BCLxL upregulation). Moreover, we observed that CLL cells from the lymph nodes at disease progression are less sensitive to venetoclax compared to ones present in peripheral blood. Strikingly, we could recapitulate this phenotype by maintaining CLL cells in culture under conditions that mimic the lymphoid tissue microenvironment. Interestingly, such culture conditions promote the growth of more activated CLL cells which express an altered repertoire of BCL2 family proteins that probably accounts for the reduced sensitivity to venetoclax. Taken together, our studies will help us understand why resistance emerges and have significant implications for how venetoclax is best used, for preventing the development of therapy resistance or to develop strategies to tackle resistance once it emerges. [ABSTRACT FROM AUTHOR]