301 Godwin Ave
Midland Park NJ 07432
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FOXP3-miR-146-NF-ÎºB Axis and Therapy for Precancerous Lesions in Prostate. - Cancer research
The tumor-suppressive activity of FOXP3 has been observed in tumor initiation, but the underlying mechanism still remains largely unknown. Here, we identified a FOXP3-microRNA-146 (miR-146)-NF-ÎºB axis in vitro and in vivo in prostate cancer cells. We observed that FOXP3 dramatically induced the expression of miR-146a/b, which contributed to transcriptional inhibition of IRAK1 and TRAF6, in prostate cancer cell lines. Tissue-specific deletion of Foxp3 in mouse prostate caused a significant reduction of miR-146a and upregulation of NF-ÎºB activation. In addition, prostatic intraepithelial neoplasia lesions were observed in miR-146a-mutant mice as well as in Foxp3-mutant mice. Notably, the NF-ÎºB inhibitor bortezomib inhibited cell proliferation and induced apoptosis in prostate epithelial cells, attenuating prostatic intraepithelial neoplasia formation in Foxp3-mutant mice. Our data suggest that the FOXP3-miR-146-NF-ÎºB axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146-NF-ÎºB axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects.Â©2015 American Association for Cancer Research.
Boomerang recruitment: bridging the gap. - Nursing economic$
In today's competitive health care recruitment environment, one of the most cost-effective and successful recruitment strategies is alumni or "boomerang" recruitment. A proven business model, alumni recruitment is just beginning to be used in a significant way in the health care arena. The cost to recruit alumni is much lower than for those in the general workforce and the alumni population is a known quantity. Alumni will assimilate much more easily into your corporate culture, will need less orientation and onboarding, and will be more productive.
High-tech, high-touch recruitment: an oxymoron? - Nursing economic$
A combination of factors has diluted the recruitment experience and created a confluence of elements similar to a perfect storm. Recruitment has morphed from a high-touch experience to a high-tech process. Though we can't go back to those halcyon pre-Internet days, we do need to find a better approach than our current technology-based, fragmented recruitment process. The ideal recruitment scenario would be a marriage of high tech and high touch. We must drive the technology, not let the technology dictate our process.
Development and validation of Patient Reported Impact of Spasticity Measure (PRISM). - Journal of rehabilitation research and development
Persons with spinal cord injury (SCI) may experience a range of symptoms typically labeled "spasticity." Previous efforts to develop assessment tools that measure spasticity have failed to represent the experiences of persons who live with the condition. The purpose of this multicenter study was to develop an instrument that measures the impact of spasticity on quality of life. Based on 24 semistructured interviews, a developmental form of the Patient Reported Impact of Spasticity Measure (PRISM) was constructed. The developmental PRISM was administered to 180 persons at five sites. Subscales were developed based on factor analytic results. Evidence for the reliability and validity of the scores was evaluated. Seven subscales were developed, including one that measures the positive effects of spasticity. Results of reliability and validity assessments indicate that the PRISM subscale scores effectively measure the impact of spasticity in the population of veterans with SCI.
Workforce shortages are a global issue. - Nursing economic$
A consortium of international organizations convened a first-ever Global Health Care Workforce Conference to discuss the worldwide shortages of health care workers and the migration patterns of health care workers from developing nations to the first world. Over 300 participants from 47 countries, including one-third from developing countries, discussed a variety of critical issues ranging from global immigration, recruitment, economics, to partnerships. Results, recommendations, and actionable items generated from the conference, as well as ways to put these ideas into practice, will be critical for sustaining and improving world health and the plight and numbers of health care providers.
Spasticity experience domains in persons with spinal cord injury. - Archives of physical medicine and rehabilitation
To understand the everyday life experiences of persons who have spasticity associated with spinal cord injury (SCI).Applied ethnographic design.Patients' homes and rehabilitation clinics.Twenty-four people with SCI who experience spasticity.Not applicable.Domains identified through qualitative analysis of in-depth open-ended interviews.Domain analysis revealed 7 domains: physical, activity, emotional, economic, interpersonal, management, and cognitive. Descriptive subcategories within each domain were identified. Patients personalized the meaning of spasticity and expressed their understandings of the condition in ways that may not be consistent with clinical definitions. Some patients suggested that being able to control spasticity was preferable to total suppression.Spasticity-related interventions need to be aimed at what matters most to the patient. It is critical for clinicians to understand patients' experiences to make accurate assessments, effectively evaluate treatment interventions, and select appropriate management strategies. When providers reconfigure patients' descriptions to fit neatly with a biomedical understanding of spasticity without carefully assessing the descriptions in terms of what matters most to patients, a potential risk for misappropriating interventions may arise.
Safety assessment of 4'-thio-beta-D-arabinofuranosylcytosine in the beagle dog suggests a drug-induced centrally mediated effect on the hypothalamic-pituitary-adrenal axis. - International journal of toxicology
4'-Thio-beta-D-arabinofuranosylcytosine (OSI-7836) is a nucleoside analogue with structural similarity to gemcitabine and cytarabine (ara-C). Myelosuppression, reversible transaminase elevations, and flu-like symptoms are common side effects associated with human use of gemcitabine and ara-C. Fatigue is also associated with the use of gemcitabine and OSI-7836 in humans. To better understand the toxicity of OSI-7836, subchronic studies were conducted in dogs. OSI-7836 was administered on days 1 and 8 or on days 1, 2, and 3 of a 21-day dose regimen. These schedules attempted to match clinical trial dosing regimens. Routine toxicity study end points demonstrated that OSI-7836 was primarily cytotoxic to the gastrointestinal tract, bone marrow, and testes; the myelotoxicity was mild and reversible. Plasma pharmacokinetics were dose-linear with an elimination half-life of 2.2 h. Follow-up single dose experiments in dogs assessed drug effects on lymphocyte subpopulations and on adrenal and thyroid function. Populations of T and B cells were equally reduced following OSI-7836 administration. There were no adverse effects on thyroid function, but there were marked reductions in circulating cortisol and adrenocorticotropic hormone concentrations suggesting a centrally mediated impairment of the hypothalamic-pituitary-adrenal axis. These findings show a toxicological profile with OSI-7836 similar to other nucleoside analogues and suggest that the beagle is a model for studying one possible cause of OSI-7836-related fatigue, impaired function of the hypothalamic-pituitary-adrenal axis.
OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. - Cancer research
OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain receptor (KDR), which is currently being evaluated in clinical studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact cells and also inhibits these targets in vivo following oral dosing. We have investigated the relationships between the potency observed in cell-based assays in vitro, the plasma exposure levels achieved following oral dosing, the time course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this dose range was associated with antitumor activity. Similarly, prolonged inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral doses of 100 to 200 mg/kg, which was the dose level associated with significant antitumor activity in this model as well as in the majority of other xenograft models tested. The data suggest that antitumor activity of OSI-930 in mouse xenograft models is observed at dose levels that maintain a significant level of inhibition of the molecular targets of OSI-930 for a prolonged period. Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930 at these effective dose levels provides an estimate of the target plasma concentrations that may be required to achieve prolonged inhibition of Kit and KDR in humans and which would therefore be expected to yield a therapeutic benefit in future clinical evaluations of OSI-930.
Study: who are the men in nursing? - Imprint
Many of the closing comments that respondents shared revisited areas of concern and optimism about the nursing profession and men's place within it. Emphasis was placed on the need to recruit more men and minorities into the profession, confront stereotypes, and improve the general awareness and knowledge of what the profession has to offer to all its members. Just as in the student survey, we were struck by how articulate and passionate respondents were about nursing. Countless respondents indicated that nursing was a 'calling'; that they especially enjoyed 'making a difference' and how unique nursing is for that reason. We also appreciated the humor and self-confidenc they demonstrated about the reality of being a minority in the profession, and their 'just do it' mindset.
Incorporation of OSI-7836 into DNA of Calu-6 and H460 xenograft tumors. - Cancer chemotherapy and pharmacology
OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell death. This hypothesis has been examined by measuring and comparing the incorporation of ara-C, OSI-7836, and gemcitabine (dFdC) into DNA of cultured cells and by investigating the role of deoxycytidine kinase in OSI-7836 toxicity. We report here additional studies in which the role of cell cycling on OSI-7836 toxicity was investigated and incorporation of OSI-7836 into DNA of xenograft tumors measured. The role of the cell cycle was examined by comparing the toxicity of OSI-7836 in A549 NSCLC cells that were either in log phase growth or had reached confluence. A novel validated LC-MS/MS assay was developed to quantify the concentrations of OSI-7836 in DNA from Calu-6 and H460 human tumor xenografts in mice. Results showed that apoptosis induced by OSI-7836 was markedly greater in cycling cells than in confluent non-cycling cells despite only a modest increase in intracellular OSI-7836 triphosphate concentration. The LC-MS/MS assay developed to measure OSI-7836 incorporation into DNA had an on-column detection limit of 0.25 fmol, a quantification limit of 0.5 fmol, and a sensitivity of approximately 0.1 pmol OSI-7836/micromol dThy. Concentrations of OSI-7836 in splenic DNA (0.4 pmol OSI-7836/micromol dThy) averaged fivefold less than the average concentration in Calu-6 and H460 xenograft DNA (3.0 pmol OSI-7836/micromol dThy) following a 400 mg/kg dose of OSI-7836. Concentrations of OSI-7836 in Calu-6 tumor DNA isolated 24 h following a dose of 400, 1000, or 1600 mg OSI-7836/kg were approximately 1.3, 1 and 1.3 pmol OSI-7836/micromol dThy, respectively. Concentrations of OSI-7836 in DNA from H460 and Calu-6 xenografts did not appear to increase during repeated administration of 400 mg OSI-7836/kg on days 1, 4, 7, and 10. The majority of OSI-7836 in DNA from Calu-6 and H460 tumors of mice dosed with 1600 mg/kg was located at internal nucleotide linkages, similar to dFdC and ara-C. In conclusion, cell cycling studies supported the hypothesis that OSI-7836 cytotoxicity is dependent upon DNA synthesis. A validated LC-MS/MS assay was developed that could quantify OSI-7836 in DNA from tissues. The assay was used to show that OSI-7836 was incorporated in internal linkages in tumor DNA in a manner that was dose-independent at the doses tested and did not appear to accumulate during repeated dosing. The results suggest that if DNA incorporation is a toxic event, the relationships between administered dose, DNA incorporation, and toxicity are complex.
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301 Godwin Ave Midland Park, NJ 07432
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