Repurposing metformin for cancer treatment: current clinical studies.

In recent years, several studies have presented evidence suggesting a potential role for metformin in anti-cancer therapy. Preclinical studies have demonstrated several anticancer molecular mechanisms of metformin including mTOR inhibition, cytotoxic effects, and immunomodulation. Epidemiologic data have demonstrated decreased cancer incidence and mortality in patients taking metformin. Several clinical trials, focused on evaluation of metformin as an anti-cancer agent are presently underway. Data published from a small number of completed trials has put forth intriguing results. Clinical trials in pre-surgical endometrial cancer patients exhibited a significant decrease in Ki67 with metformin monotherapy. Another interesting observation was made in patients with breast cancer, wherein a trend towards improvement in cancer proliferation markers was noted in patients without insulin resistance. Data on survival outcomes with the use of metformin as an anti-cancer agent is awaited. This manuscript will critically review the role of metformin as a potential cancer treatment

Structured Engagement for a Multi-Institutional Collaborative to Tackle Challenges and Share Best Practices

A National Consortium for Synergistic Undergraduate Mathematics via Multi-institutional Interdisciplinary Teaching Partnerships (SUMMIT-P), funded by the National Science Foundation, is a multi-institutional consortium with members from twelve institutions. The consortium adapted two protocols developed by the School Reform Initiative to: 1. provide advice on challenges or dilemmas a consortium member is facing and 2. share project successes with consortium members. The two protocols—a Modified Descriptive Consultancy protocol and a Modified Success Analysis with Reflective Questions protocol—provide a structured format for these discussions. This paper provides an in-depth description of the two protocols and how they have been used for this project. Examples demonstrating the impact of the protocols are provided by the co-authors

Combined histomorphometric and gene-expression profiling applied to toxicology

We have developed a unique methodology for the combined analysis of histomorphometric and gene-expression profiles amenable to intensive data mining and multisample comparison for a comprehensive approach to toxicology. This hybrid technology, termed extensible morphometric relational gene-expression analysis (EMeRGE), is applied in a toxicological study of time-varied vehicle- and carbon-tetrachloride (CCl(4))-treated rats, and demonstrates correlations between specific genes and tissue structures that can augment interpretation of biological observations and diagnosis

Talking Points on Publicly Engaged Scholarship at IUPUI

Talking Points on Publicly Engaged Scholarship at IUPUI Informed by Public Scholarship at Indiana University-Purdue University Indianapolis, a concept paper written by the Faculty Learning Community (FLC) on Public Scholarship and refined through ongoing FLC work between 2015-18 in collaboration with faculty across the campus and with nationally-recognized scholars

Lunar Dust Effects on Spacesuit Systems: Insights from the Apollo Spacesuits

Systems and components of selected Apollo A7L/A7LB flight-article spacesuits that were worn on the lunar surface have been studied to determine the degree to which they suffered contamination, abrasion and wear or loss of function due to effects from lunar soil particles. Filter materials from the lithium hydroxide (LiOH) canisters from the Apollo Command Module were also studied to determine the amount and type of any lunar dust particles they may have captured from the spacecraft atmosphere. The specific spacesuit study materials include the outermost soft fabric layers on Apollo 12 and 17 integrated thermal micrometeorite garment assemblies and outermost fabrics on Apollo 17 extravehicular pressure gloves. In addition, the degree of surface wear in the sealed wrist rotation bearing from Apollo 16 extravehicular and intravehicular pressure gloves was evaluated and compared. Scanning electron microscope examination of the Apollo 12 T-164 woven TeflonO fabric confirms the presence of lunar soil particles and the ability of these particles to cause separation and fraying of the Teflon fibers. Optical imaging, chemical analysis and particle sampling applied to the outer fabric of the Apollo 17 spacesuit has identified Ti as a potentially useful chemical marker for comparing the amount of lunar soil retained on different areas of the spacesuit outer fabric. High-yield particle sampling from the Apollo 17 fabric surfaces using adhesive tape found 80% of particles on the fabric are lunar soil particles averaging 10.5 m in diameter, with the rest being intrinsic fabric materials or environmental contaminants. Analysis of the mineralogical composition of the lunar particles found that on a grain-count basis the particle population is dominated by plagioclase feldspar and various types of glassy particles derived mostly from soil agglutinates, with a subordinate amount of pyroxene. On a grain size basis, however, the pyroxene grains are generally a factor of 2 larger than glass and plagioclase, so conversion of the data to a modal (volume %) basis results in pyroxene becoming the modally dominant particle type with glass and plagioclase significantly less abundant. When comparisons are made to the modal composition of lunar soil at the Apollo 17 landing site, the results suggest that pyroxene particles have overall better retention on the spacesuit outer fabric compared to plagioclase and especially glass. Scanning electron microscopy revealed no measureable difference in the amount of wear and abrasion in the wrist rotation bearing of an Apollo 16 pressure glove worn only in the spacecraft and one worn only for extravehicular activity on the lunar surface. The results suggest either that the bearing prevented entry of lunar dust, or that dust was not sufficiently abrasive to damage the bearing, or both

Evidence-based planning and costing palliative care services for children : novel multi-method epidemiological and economic exemplar

Background: Children’s palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children’s hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Methods: Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. Results: The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children’s palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Conclusions: Findings make a significant contribution to population-based needs assessment and commissioning methodology in children’s palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

Genome Sequence of the Deltaproteobacterial Strain NaphS2 and Analysis of Differential Gene Expression during Anaerobic Growth on Naphthalene

Anaerobic polycyclic hydrocarbon (PAH) degradation coupled to sulfate reduction may be an important mechanism for in situ remediation of contaminated sediments. Steps involved in the anaerobic degradation of 2-methylnaphthalene have been described in the sulfate reducing strains NaphS3, NaphS6 and N47. Evidence from N47 suggests that naphthalene degradation involves 2-methylnaphthalene as an intermediate, whereas evidence in NaphS2, NaphS3 and NaphS6 suggests a mechanism for naphthalene degradation that does not involve 2-methylnaphthalene. To further characterize pathways involved in naphthalene degradation in NaphS2, the draft genome was sequenced, and gene and protein expression examined.Draft genome sequencing, gene expression analysis, and proteomic analysis revealed that NaphS2 degrades naphthoyl-CoA in a manner analogous to benzoyl-CoA degradation. Genes including the previously characterized NmsA, thought to encode an enzyme necessary for 2-methylnaphthalene metabolism, were not upregulated during growth of NaphS2 on naphthalene, nor were the corresponding protein products. NaphS2 may possess a non-classical dearomatizing enzyme for benzoate degradation, similar to one previously characterized in Geobacter metallireducens. Identification of genes involved in toluene degradation in NaphS2 led us to determine that NaphS2 degrades toluene, a previously unreported capacity. The genome sequence also suggests that NaphS2 may degrade other monoaromatic compounds.This study demonstrates that steps leading to the degradation of 2-naphthoyl-CoA are conserved between NaphS2 and N47, however while NaphS2 possesses the capacity to degrade 2-methylnaphthalene, naphthalene degradation likely does not proceed via 2-methylnaphthalene. Instead, carboxylation or another form of activation may serve as the first step in naphthalene degradation. Degradation of toluene and 2-methylnaphthalene, and the presence of at least one bss-like and bbs-like gene cluster in this organism, suggests that NaphS2 degrades both compounds via parallel mechanisms. Elucidation of the key genes necessary for anaerobic naphthalene degradation may provide the ability to track naphthalene degradation through in situ transcript monitoring