Distilling a Collection: Creating a Distilling, Fermenting, and Brewing Special Collection at the James E. Walker Library

This essay recounts the steps we took to launch the new Distilling, Fermenting, and Brewing Collection in our Special Collections department. It began with the routine task of weeding our general collection but quickly led to other activities which included a broader collection analysis; consideration of campus, local and state resources; consultation with development and fundraising staff; and research in the anti-quarian trade. Knowing what we had and what we could acquire in the book market, surmising the po-tential for private and industry support, and understanding the multiple scholarly possibilities embed-ded in our collection, we embarked on building a resource that can attract students, faculty, outside re-searchers, and private supporters

Predictors of Adherence to Nutrition Recommendations in People With Non- Insulin-Dependent Diabetes Mellitus

The purpose of this study was to determine how the components of psychosocial adjustment to diabetes predict adherence to nutrition recommendations based on self-reported successful completion of contingency contracts. The relationships between the components of psychosocial adjustment and adherence to nutrition recommendations were examined in a convenience sample of patients with non-insulin- dependent diabetes mellitus participating in a contingency contracting intervention with nurses. Patients completed a standardized instrument, the Diabetes Care Profile, at the time they were enrolled into this randomized clinical trial. High and low levels of adherence to nutrition recommendations were identified by a median split of the number of contingency contracts completed for adherence to nutrition recommendations. Subjects who reported higher regimen adherence and a higher support ratio (received more diabetes-specific social support than desired) were significantly less likely to engage in contingency contracting for adherence to nutrition recommendations .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68967/2/10.1177_014572179702300206.pd

Orally Bioavailable Dual MMP-1/MMP-14 Sparing, MMP-13 Selective Alpha-sulfone Hydroxamates

A series of phenyl piperidine α-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats

Protocol for Universal Newborn Hearing Screening in Ontario

This document describes the Ontario Infant Hearing Program’s (IHP) protocol for universal newborn hearing screening (UNHS) of newborns and infants. It overrides all previous protocols on this subject provided by the IHP. The primary audience for this protocol is those who conduct newborn hearing screening within the IHP. All newborn and infant hearing screening funded by the Ontario Ministry of Children, Community and Social Services (MCCSS) must be carried out in full accordance with this protocol. It is based on continuous review of the best available scientific and clinical evidence and expert consultation complemented by consultation and collaboration with other major Early Hearing Detection and Intervention (EHDI) programs in Canada and worldwide

Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)

Background: Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation. Methods: 7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naive, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS. Results: Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization. Conclusions: Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity

The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans

Ballistic magnetoresistance in nickel single-atom conductors

Large ballistic magnetoresistance (BMR) has been measured in Ni single-atom conductors electrodeposited between microfabricated thin films. These measurements irrefutably eliminate any magnetostriction related artifacts in the BMR effect.Comment: 12 pages, 3 Figure

PRKACA Mediates Resistance to HER2-Targeted Therapy in Breast Cancer Cells and Restores Anti-Apoptotic Signaling

Targeting HER2 with antibodies or small molecule inhibitors in HER2-positive breast cancer leads to improved survival, but resistance is a common clinical problem. To uncover novel mechanisms of resistance to anti-HER2 therapy in breast cancer, we performed a kinase open reading frame (ORF) screen to identify genes that rescue HER2-amplified breast cancer cells from HER2 inhibition or suppression. In addition to multiple members of the MAPK and PI3K signaling pathways, we discovered that expression of the survival kinases PRKACA and PIM1 rescued cells from anti-HER2 therapy. Furthermore, we observed elevated PRKACA expression in trastuzumab-resistant breast cancer samples, indicating that this pathway is activated in breast cancers that are clinically resistant to trastuzumab-containing therapy. We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro-apoptotic protein BAD, thereby permitting survival signaling through BCL-XL. Pharmacological blockade of BCL-XL/BCL-2 partially abrogated the rescue effects conferred by PRKACA and PIM1, and sensitized cells to lapatinib treatment. These observations suggest that combined targeting of HER2 and the BCL-XL/BCL-2 anti-apoptotic pathway may increase responses to anti-HER2 therapy in breast cancer and decrease the emergence of resistant disease

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

A Multisite Study of Nurse-Reported Perceptions and Practice of ABCDEF Bundle Components

Objectives: ABCDEF bundle implementation in the Intensive Care Unit (ICU) is associated with dose dependent improvements in patient outcomes. The objective was to compare nurse attitudes about the ABCDEF bundle to self-reported adherence to bundle components. Research methodology/design: Cross-sectional study. Setting: Nurses providing direct patient care in 28 ICUs within 18 hospitals across the United States. Main outcome measures: 53-item survey of attitudes and practice of the ABCDEF bundle components was administered between November 2011 and August 2015 (n = 1661). Results: We did not find clinically significant correlations between nurse attitudes and adherence to Awakening trials, Breathing trials, and sedation protocol adherence (rs = 0.05-0.28) or sedation plan discussion during rounds and Awakening and Breathing trial Coordination (rs = 0.19). Delirium is more likely to be discussed during rounds when ICU physicians and nurse managers facilitate delirium reduction (rs = 0.27-0.36). Early mobilization is more likely to occur when ICU physicians, nurse managers, staffing, equipment, and the ICU environment facilitate early mobility (rs = 0.36-0.47). Physician leadership had the strongest correlation with reporting an ICU environment that facilitates ABCDEF bundle implementation (rs = 0.63-0.74). Conclusions: Nurse attitudes about bundle implementation did not predict bundle adherence. Nurse manager and physician leadership played a large role in creating a supportive ICU environment