Collaborating with Businesses to Support and Sustain Research

Financial assistance is necessary for sustaining research at universities. Business collaborations are a potential means for obtaining these funds. To secure funding, understanding the process for obtaining these business funds is important for nursing faculty members. Although faculty rarely request funding from businesses, they are often in a position to solicit financial support due to existing relationships with clinical agency administrators, staff, and community leaders. The economic support received from businesses provides outcomes in nursing research, research education, academic–service partnerships, and client health care. This article describes the steps and processes involved in successfully obtaining research funding from businesses. In addition, case examples for securing and maintaining funding from health care agencies (evidence-based practice services) and from a health manufacturing company (product evaluation) are used to demonstrate the process

Science on a Shoestring: Building Nursing Knowledge With Limited Funding

Building the science for nursing practice has never been more important. However, shrunken federal and state research budgets mean that investigators must find alternative sources of financial support and develop projects that are less costly to carry out. New investigators often build beginning programs of research with limited funding. This article provides an overview of some cost-effective research approaches and gives suggestions for finding other sources of funding. Examples of more cost-effective research approaches include adding complementary questions to existing funded research projects; conducting primary analysis of electronic patient records and social media content; conducting secondary analysis of data from completed studies; reviewing and synthesizing previously completed research; implementing community-based participatory research; participating in collaborative research efforts such as inter-campus team research, practice-based research networks (PBRNs), and involving undergraduate and doctoral students in research efforts. Instead of relying on funding from the National Institutes of Health (NIH) and other government agencies, nurse researchers may be able to find support for research from local sources such as businesses, organizations, or clinical agencies. Investigators will increasingly have to rely on these and other creative approaches to fund and implement their research programs if granting agency budgets do not significantly expand

The role of p53 and CYLD in mitochondrial death pathways and mechanisms of neuronal necroptosis

Neuronal cell death causes progressive loss of brain tissue and function after acute brain injury and in chronic neurodegenerative diseases. Although the pathological features of stroke and brain trauma or Alzheimer’s and Parkinson’s disease differ greatly, the underlying neuronal damage shares common molecular and cellular mechanisms. Despite extensive research and increasing knowledge on the molecular pathology, no efficient therapy has been born from these efforts until today. As a promising concept to overcome this plight, it has been suggested to enhance endogenous survival signaling pathways like the transcription factor NF-κB and thus obtain neuroprotection. Increasing neuroprotective NF-κB signaling can be achieved by blocking repressors of NF-κB transcriptional activity such as p53 and CYLD. Both factors may mediate cell death by mechanisms dependent on and independent of NF-ΚB signaling. Therefore, the major aim of this study was to explore the roles of p53 and CYLD in neuronal cell death and to connect their detrimental effects with NF-κB activity. This issue was addressed in immortalized mouse hippocampal HT-22 neurons and in primary neuronal cultures exposed to glutamate toxicity. Furthermore, an in vivo model system of traumatic brain injury was employed to compare infarct development after controlled cortical impact in wild-type and CYLD-/- mice. The present study revealed that both approaches, inhibiting p53 and CYLD successfully preserved mitochondrial integrity and function, and significantly attenuated neuronal cell death. Surprisingly, however, the pronounced neuroprotective effect of the p53-inhibitor pifithrin-α occurred independently of enhanced NF-κB activity in HT-22 cells. In addition, neuroprotection induced by silencing of CYLD was completely independent of NF-κB, despite of the previously established role of CYLD as a negative regulator of NF-κB in keratinocytes. In line with that notion, the NF-κB subunit expression and NF-κB transcriptional activity were not significantly altered in HT-22 neurons undergoing glutamate dependent cell death. In conclusion, these data suggested that the NF-κB pathway was neither significantly affected by glutamate dependent cell death, nor did it mediate the neuroprotective response of CYLD and p53 inhibition in this model system of glutamate toxicity. Interestingly, inhibiting p53 with pifithrin-α maintained mitochondrial morphology and mitochondrial membrane potential in HT-22 cells. This effect occurred independently of p53 dependent transcription. Investigating the underlying cause of neuroprotection associated with CYLD depletion, it was unveiled that glutamate-induced oxytosis in HT-22 cells occurred through mechanisms of necroptosis. This conclusion is based on the detection of RIP1/RIP3 complexes as a hallmark of necroptotic cell death in HT-22 cells exposed to glutamate. Further, silencing either RIP-kinase provided strong protection of the cells. Repressing CYLD, in turn, prevented the formation of the RIP1/RIP3 necrosome, suggesting that inhibition of necroptosis was the underlying mechanism of neuroprotection after CYLD depletion. In contrast, CYLD depletion had no effect on cell death in a model of glutamate excitotoxicity in primary cultured neurons, while inhibition of RIP1 kinase by necrostatin-1 significantly enhanced neuronal survival. These data suggest a CYLD independent but RIP1 dependent mechanism of glutamate toxicity in primary neurons, which requires further investigation. In vivo, however, using a model of traumatic brain injury, CYLD knockout mice showed a significantly reduced infarct size compared to wild-type littermates suggesting a potent neuroprotective effect inherent with CYLD repression. In summary the data from this thesis highlight a yet unknown role of CYLD in neuronal cell death and unravel CYLD and p53-dependent mechanisms of cell death as a putative therapeutic approach for the treatment of acute and chronic neurodegenerative diseases. Future research, however, is warranted to further elucidate the exact mechanisms leading to CYLD and RIP-kinase activation in neurons and to determine the exact molecular link to mitochondria

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

Jones v. Chagrin Falls: Muddying the Statutory Waters of Ohio\u27s Administrative Law Appeal Process

The common-law doctrine of failure to exhaust administrative remedies has generally been held to be a prerequisite to judicial review in statutorily defined administrative law appeal processes. Similarly, the United States Supreme Court in interpreting the federal administrative law appeal process, and the case law on Ohio\u27s administrative law appeal process, have found that the doctrine of exhaustion is a jurisdictional bar to a declaratory judgment action except while challenging the constitutionality of a municipal or administrative decision. However, according to the holding in Jones v. Chagrin Falls, this may no longer be the case in Ohio. This article discusses the Jones case in detail, starting with the factual and procedural history in Parts II, and then moving on to the court’s opinion and rationale in Part III. The article finishes up with the author’s overall analysis of the decision in Part IV