School-Based Mental Health Screening: Improving Outcomes Through Interprofessional Communication and Collaboration

For the adolescent population, the immediate impact a mental health disorder has on academics,relationships, and even suicide risk cannot be understated. Access to mental health care in low socioeconomic communities for adolescents is fraught with barriers. These include lack of transportation, lack of insurance coverage, fear of stigma, and a fundamental lack of knowledge regarding available resources. It is therefore a two-fold problem that exists for those in the care and observation of these adolescents; underutilization of appropriate routine screening and navigation to access care. This project aimed to remediate both of these issues at a high school located in Alameda County, California. The school currently provides access to an on-site School-Based Health Center (SBHC) in addition to several guidance counselors and ancillary support staff. Even with these available resources, the organization lacked a protocol that utilizes a universal psychosocial screening tool as well as interprofessional collaboration (IPC) to facilitate case management of students identified for the need of emotional or behavioral health services. The project consisted of the introduction of a validated psychosocial screening tool and a model for IPC delivered via a one-hour educational workshop to each of the identified stakeholders at the high school campus. Pre- and post-survey results indicate an increase in knowledge in mental health literacy as well as proficiency in the use of the tools presented. Additional qualitative feedback indicates a willingness among all stakeholders to adopt the IPC activities presented and two-month follow up interviews demonstrates a modest preliminary application of effective screening use

The Role of the Clinical Nurse Leader in Reintroducing and Sustaining a Successful Cancer Risk Assessment Program in a Community Hospital Setting

Abstract The goal of implementing a comprehensive cancer risk assessment (CRA) program prompted the evaluation of a community-based breast center microsystem and previous CRA program for feasibility and sustainability. The development of a value proposition by the Clinical Nurse Leader student highlights the role in the advancement of the nursing profession as an interdisciplinary leader. Review of current literature facilitated development of program structure and identification of downstream revenue sources. Data analysis includes historical patient volume, screening and procedural reimbursement rates, population statistics and organization market share, and program financial impacts. Data synthesis reveals a CRA program demonstrates potential revenue generation of $283,996.20 by the second year of implementation. The associated costs related to staffing and start up capital total$231,988.00, determining an estimated break-even point to be within the first 18 months of the program. With evidence demonstrating improvements in patient outcomes related to early disease detection, the recommendation to the institution is therefore to invest in implementing a comprehensive cancer risk assessment program

Differential regulation of myeloid leukemias by the bone marrow microenvironment

Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow microenvironment (BMM)1, and may be the cause of relapse following chemotherapy.2 Targeting the niche is a novel strategy to eliminate persistent and drug-resistant LSC. CD443,4 and IL-65 have been implicated previously in the LSC niche. Transforming growth factor (TGF)-β1 is released during bone remodeling6 and plays a role in maintenance of CML LSCs7, but a role for TGF-β1 from the BMM has not been defined. Here, we show that alteration of the BMM by osteoblastic cell-specific activation of the parathyroid hormone (PTH) receptor8,9 attenuates BCR-ABL1-induced CML-like myeloproliferative neoplasia (MPN)10 but enhances MLL-AF9-induced AML11 in mouse transplantation models, possibly through opposing effects of increased TGF-β1 on the respective LSC. PTH treatment caused a 15-fold decrease in LSCs in wildtype mice with CML-like MPN, and reduced engraftment of immune deficient mice with primary human CML cells. These results demonstrate that LSC niches in chronic and acute myeloid leukemias are distinct, and suggest that modulation of the BMM by PTH may be a feasible strategy to reduce LSC, a prerequisite for the cure of CML

A BCR-ABL Mutant Lacking Direct Binding Sites for the GRB2, CBL and CRKL Adapter Proteins Fails to Induce Leukemia in Mice

The BCR-ABL tyrosine kinase is the defining feature of chronic myeloid leukemia (CML) and its kinase activity is required for induction of this disease. Current thinking holds that BCR-ABL forms a multi-protein complex that incorporates several substrates and adaptor proteins and is stabilized by multiple direct and indirect interactions. Signaling output from this highly redundant network leads to cellular transformation. Proteins known to be associated with BCR-ABL in this complex include: GRB2, c-CBL, p62DOK, and CRKL. These proteins in turn, link BCR-ABL to various signaling pathways indicated in cellular transformation. In this study we show that a triple mutant of BCR-ABL with mutations of the direct binding sites for GRB2, CBL, p62DOK and CRKL, is defective for transformation of primary hematopoietic cells in vitro and in a murine CML model, while it retains the capacity to induce IL-3 independence in 32D cells. Compared to BCR-ABL, the triple mutant's ability to activate the MAP kinase and PI3-kinase pathways is severely compromised, while STAT5 phosphorylation is maintained, suggesting that the former are crucial for the transformation of primary cells, but dispensable for transformation of factor dependent cell lines. Our data suggest that inhibition of BCR-ABL-induced leukemia by disrupting protein interactions could be possible, but would require blocking of multiple sites

Mig-6 is a negative regulator of the epidermal growth factor receptor signal

In contrast to signal generation and transmission, the mechanisms and molecules that negatively regulate receptor tyrosine kinase (RTK) signaling are poorly understood. Here we characterize Mig-6 as a novel negative feedback regulator of the epidermal growth factor receptor (EGFR) and potential tumor suppressor. Mig-6 was identified in a yeast two-hybrid screen with the kinase active domain of the EGFR as bait. Upon EGF stimulation Mig-6 binds to the EGFR involving a highly acidic region between amino acids 985-995. This interaction is kinase activity-dependent, but independent of tyrosine 992. Mig-6 overexpression results in reduced activation of the mitogen- activated protein kinase ERK2 in response to EGF, but not FGF or PDGF, stimulation and in enhanced receptor internalization without affecting the rate of degradation. The induction of Mig-6 mRNA expression in response to EGF, but not FGF, indicates the existence of a negative regulatory feedback loop. Consistent with these findings, a possible role as tumor suppressor is indicated by Mig-6-mediated inhibition of EGFR overexpression-induced transformation of Rat1 cells

Biol. Chem.

In contrast to signal generation and transmission, the mechanisms and molecules that negatively regulate receptor tyrosine kinase (RTK) signaling are poorly understood. Here we characterize Mig-6 as a novel negative feedback regulator of the epidermal growth factor receptor (EGFR) and potential tumor suppressor. Mig-6 was identified in a yeast two-hybrid screen with the kinase active domain of the EGFR as bait. Upon EGF stimulation Mig-6 binds to the EGFR involving a highly acidic region between amino acids 985-995. This interaction is kinase activity-dependent, but independent of tyrosine 992. Mig-6 overexpression results in reduced activation of the mitogen- activated protein kinase ERK2 in response to EGF, but not FGF or PDGF, stimulation and in enhanced receptor internalization without affecting the rate of degradation. The induction of Mig-6 mRNA expression in response to EGF, but not FGF, indicates the existence of a negative regulatory feedback loop. Consistent with these findings, a possible role as tumor suppressor is indicated by Mig-6-mediated inhibition of EGFR overexpression-induced transformation of Rat1 cells