Digital Commons Network^™

A Novel Runx2 Missense Mutation Predicted To Disrupt Dna Binding Causes Cleidocranial Dysplasia In A Large Chinese Family With Hyperplastic Nails, Shaohua Tang, Qiyu Xu, Xueqin Xu, Jicheng Du, Xuemei Yang, Yusheng Jiang, Xiaoqin Wang, Nancy Speck, Taosheng Huang

Dartmouth Scholarship

Background: Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.

Methods: Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation. We sequenced the coding region of the RUNX2 gene for the mutation and phenotype analysis.

Results: The family carries a c.T407C (p.L136P) mutation in the DNA- and CBFβ-binding Runt domain of RUNX2. Based on the crystal structure, we predict this …

Illness Stories: From Recognizing The Significance In Care To Planning My Own Storied Practice, Jane Lachance

Critical and Creative Thinking Capstones Collection

In this paper, stories of illness are identified as belonging to a specific genre of story that represents an ill person's interpretation of experience and hence the meaning(s) of illness. The ill person is recognized as member of a family embedded in a social setting with cultural mores that contribute to experience and meanings. The meaning of illness is significant because it affects the care of illness. This paper focuses on chronic illness, an illness without cure that is managed over a lifetime and is characterized by remission and exacerbation of symptoms. Our current bio-medical health care system reframes the …

Identifying Methods Nurse Managers Can Implement To Foster A Supportive Environment For Staff Where Disruptive Behavior Exists, Kathleen Leavitt

Critical and Creative Thinking Capstones Collection

We can all imagine the ideal work environment, where you are respected, empowered, and provided with the resources to perform to the best of your ability everyday. Your skills would be acknowledged and the challenging work that is accomplished each day would be appreciated by peers, team members, and managers. However, in my work environment, an operating room, a phenomenon called "disruptive behavior" often interrupts the ability of achieving this desired state. Initially I was focused on this behavior being displayed by physicians but was awakened to the fact that they are not the only offenders and that many caregivers …

The "Crossroads" And Beyond, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

Mice Deficient In Involucrin, Envoplakin, And Periplakin Have A Defective Epidermal Barrier., Lisa M Sevilla, Rachida Nachat, Karen R Groot, John F Klement, Jouni Uitto, Philippe Djian, Arto Määttä, Fiona M Watt

Department of Dermatology and Cutaneous Biology Faculty Papers

The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective …

Report On The U.S. Summit: "Chronic Care At The Crossroads: Exploring Solutions For Chronic Care Management", Janice L. Clarke

College of Population Health Faculty Papers

On Tuesday, July 17, 2007 in Washington, DC, Intel Corporation assembled a group of the nation’s most respected health leaders to discuss the issues surrounding chronic care and an aging population and explore solutions to these highly complex and increasingly urgent challenges for the US health care system. The highlevel summit, hosted by Intel Chairman Craig Barrett, was held in the auditorium of the National Museum for Women in the Arts and attended, either in person or via the simultaneous webcast, by presidents, chairmen, and executive directors of influential organizations including the National Business Coalition on Health, the National Medical …

Annual Report, 2006-2007, David B. Nash

College of Population Health Annual Reports

No abstract provided.

Healing The Health Care System: Summaries From The Department Of Health Policy Summer Seminar, David B. Nash, Nora Dowd Eisenhower, Rosemarie Greco, Deborah C. Meiris

College of Population Health Faculty Papers

Editorial Introduction:
The disease management field continues to evolve. The range of chronic diseases treated has expanded to include such conditions as obesity and pain management, and the care continuum now encompasses wellness, prevention, and population health. One population that is an ideal candidate for our collective efforts is that of older adults. Global and national population projections reveal the impending staggering increase in the age 65+ cohort, which will cause a sharp increase in the demand for health care and other services due to such age-related issues as multiple chronic conditions, falls, and depression.

To begin to address these …

Stem Cells: The Dawn Of A New Era For Huntington’S Disease Research, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Acetylation In Nuclear Receptor Signaling And The Role Of Sirtuins, Chenguang Wang, Michael J. Powell, Vladimir M. Popov, Richard G. Pestell

Department of Cancer Biology Faculty Papers

It has been known since the early 1970s that nuclear receptor complexes bind DNA in association with co-regulatory proteins. Characterization of these nuclear receptor coregulators has revealed diverse enzymatic activities which temporally and spatially coordinate nuclear receptor activity within the context of local chromatin in response to diverse hormone signals. Chromatin modifying proteins, which dictate the higher order chromatin structure in which DNA is packaged, in turn orchestrate orderly recruitment of nuclear receptor complexes. Modifications of histones include acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, ADP ribosylation, deimination and proline isomerization (1). At this time, we understand how a subset of these …

How Does Quality Enter Into Health Care Purchasing Decisions?, Neil I. Goldfarb, Vittorio Maio, Chureen T. Carter, Laura Pizzi, David B. Nash

College of Population Health Faculty Papers

A number of employers, business consortia, and public purchasers are promoting "value-based purchasing" as a way to improve the quality of patient care. Some purchasers are using publicly available information on health plan and provider performance to make their health plan and provider choices, while others are using their market power to drive improvements in patient care and safety. This article examines six key strategies used by purchasers.

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

Compounds of the formula having anti-tumor activity, wherein R₁ and R₂ are as described herein

Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects Of Cocaine, Aric Madayag, Doug Lobner, Kristen S. Kau, John R. Mantsch, Omer Abdulhameed, Matthew Hearing, Mark D. Grier, David A. Baker

Biomedical Sciences Faculty Research and Publications

Cocaine produces a persistent reduction in cystine–glutamate exchange via system x_c− in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System x_c− influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system x_c− activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine …

Common And Distinct Mechanisms Of Different Redox-Active Carcinogens Involved In The Transformation Of Mouse Jb6p+ Cells, Sun Yang, Bobbye J. Misner, Rita Chiu, Frank L. Meyskens Jr.

Pharmacy Faculty Articles and Research

We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H2O2 or CdCl2. Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (∼six folds) in soft agar as compared to their JB6P+ parent cells and were associated with increased intracellular reactive oxygen species (ROS) levels. Activating protein-1 (AP-1) is a family of transcription factors that are rapidly activated by elevated intracellular ROS levels, and their composition is important in the process of cellular transformation and/or tumor progression. To investigate if carcinogenesis induced by distinct carcinogens was via similar molecular mechanisms …

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Towards An Understanding Of Salient Neighborhood Boundaries: Adolescent Reports Of An Easy Walking Distance And Convenient Driving Distance, Natalie Colabianchi, Marsha Dowda, Karin A. Pfeiffer, Dwayne E. Porter, Maria João C. A. Almeida, Russell R. Pate

Faculty Publications

Numerous studies have examined the association between the surrounding neighborhood environment and physical activity levels in adolescents. Many of these studies use a road network buffer of Euclidean distance buffer around an adolescent's home to represent the appropriate geographic area for study (i.e., neighborhood). However, little empirical research has examined the appropriate buffer size to use when defining this area and there is little consistency across published research as to the buffer size used. In this study, 909 12^th grade adolescent girls of diverse racial and geographic backgrounds were asked to report their perceptions of an easy walking distance …

Oral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Buchl, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Implementing Pharmacy Informatics In College Curricula: The Aacp Technology In Pharmacy Education And Learning Special Interest Group, Ross E. Vanderbush, H. Glenn Anderson Jr., William K. Fant, Brad S. Fujisaki, Patrick M. Malone, Paul L. Price, Maria C. Pruchnicki, Teresa L. Sterling, Kara D. Weatherman, Karl G. Williams

Pharmacy Practice & Administration

Many professional organizations have initiatives to increase the awareness and use of informatics in the practice of pharmacy. Within education we must respond to these initiatives and make technology integral to all aspects of the curriculum, inculcating in students the importance of technology in practice. This document proposes 5 central domains for organizing planning related to informatics and technology within pharmacy education. The document is intended to encourage discussion of informatics within pharmacy education and the implications of informatics in future pharmacy practice, and to guide colleges of pharmacy in identifying and analyzing informatics topics to be taught and methods …

Direct Inhibition Of Cdk9 Blocks Hiv-1 Replication Without Preventing T Cell Activation In Primary Human Peripheral Blood Lymphocytes, Dominic Salerno, Muneer G Hasham, Renée Marshall Demarest, Judit Garriga, Alexander Y Tsygankov, Xavier Graña

Rowan-Virtua School of Osteopathic Medicine Departmental Research

HIV-1 transcription is essential for the virus replication cycle. HIV-1 Tat is a viral transactivator that strongly stimulates the processivity of RNA polymerase II (RNAPII) via recruitment of the cyclin T1/CDK9 positive transcription elongation factor, which phosphorylates the C-terminal domain (CTD) of RNAPII. Consistently, HIV-1 replication in transformed cells is very sensitive to direct CDK9 inhibition. Thus, CDK9 could be a potential target for anti-HIV-1 therapy. A clearer understanding of the requirements for CDK9 activity in primary human T cells is needed to assess whether the CDK9-dependent step in HIV-1 transcription can be targeted clinically. We have investigated the effects …

Reduced Intestinal Colonization Of Adult Beef Cattle By Escherichia Coli O157:H7 Tir Deletion And Nalidixic-Acid-Resistant Mutants Lacking Flagellar Expression, Gustavo Bretschneider, Emil M. Berberov, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

The importance of the Escherichia coli O157:H7 translocated intimin receptor (Tir) protein in intestinal colonization and the effect of infection with Tir⁺ strains on protection against subsequent challenge was studied in adult beef cattle. Cattle were orally inoculated (C1) with a Shiga toxin-2⁺+ E. coli O157:H7 strain that was Tir⁺ or Tir^-, and 42 days later were re-challenged (C2) with the nalidixic acid (Nal) ^R parent strain to test whether prior infection had any effect on fecal shedding. During the first 14 days post-C1, the Nal^S wildtype (WT) strain was shed at significantly …

N-Glycan Modification In Aspergillus Species, Elke Kainz, Andreas Gallmetzer, Christian Hatzl, Juergen H. Nett, Huijuan Li, Thorsten Schinko, Robert Pachlinger, Harald Berger, Yazmid Reyes-Dominguez, Andreas Bernreiter, Tillmann Gerngross, Stefan Wildt, Joseph Strauss

Dartmouth Scholarship

The production by filamentous fungi of therapeutic glycoproteins intended for use in mammals is held back by the inherent difference in protein N-glycosylation and by the inability of the fungal cell to modify proteins with mammalian glycosylation structures. Here, we report protein N-glycan engineering in two Aspergillus species. We functionally expressed in the fungal hosts heterologous chimeric fusion proteins containing different localization peptides and catalytic domains. . This strategy allowed the isolation of a strain with a functional -1,2-mannosidase producing increased amounts of N-glycans of the Man 5 GlcNAc 2 type. This strain was further engineered by the introduction of …

Barriers To Medicare Hospice Utilization: A Qualitative Study Of Maine's Medicare Hospice Providers, Judith B. Tupper Dhed, Ches, Cpps

Disability & Aging

This report, prepared for the Maine Hospice Council and funded by the Carpenter Foundation, presents findings of a qualitative study of barriers to hospice utilization. This study includes the perspectives of all 26 Medicare certified hospice providers in Maine. Significant findings of the qualitative study include: A continuing need to educate the general public about hospice and the Medicare benefit. Maine health care providers have low referral rates to the hospice programs and often misunderstand the regulations and guidelines of the hospice benefit. The referral process to hospice programs is based on fragile systems of communication, fraught with potential miscues, …

Honaker, Marion Earl, 1914-2006 (Sc 1510), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid only for Manuscripts Small Collection 1510. Letters, 1985-1997 (19); military papers, 1942-1990 (14); photos (21); newspapers clippings, 1942, 1992-2006 (5); of Marion Earl Honaker, Bowling Green, Kentucky, a Navy pharmacist mate stationed in the Pacific Area during World War II.

Public Health Campaigns To Change Industry Practices That Damage Health: An Analysis Of 12 Case Studies, Nicholas Freudenberg, Sarah Picard Bradley, Monica Serrano

Publications and Research

Industry practices such as advertising, production of unsafe products, and efforts to defeat health legislation play a major role in current patterns of U.S. ill health. Changing these practices may be a promising strategy to promote health. The authors analyze 12 campaigns designed to modify the health-related practices of U.S. corporations in the alcohol, automobile, food and beverage, firearms, pharmaceutical, and tobacco industries. The objectives are to examine the interactions between advocacy campaigns and industry opponents; explore the roles of government, researchers, and media; and identify characteristics of campaigns that are effective in changing health-damaging practices. The authors compared campaigns …

Infl Uence Of Nicotine On Positive Affect In Anhedonic Smokers, Jessica Werth Cook, Bonnie Spring, Dennis E. Mcchargue

Department of Psychology: Faculty Publications

Rationale – The possibility that individuals administer nicotine to self-regulate persistent negative affect has received interest as a possible explanation for the high prevalence of affectively vulnerable smokers. Relatively overlooked, however, is the possibility that smokers might also self-administer nicotine to elevate low positive affect. Objectives – This study examined whether nicotine administration augmented anhedonic smokers’ positive affective response to a positive mood induction. Materials and methods – Fifty regular smokers (50% female) underwent two positive mood inductions during which they smoked either a nicotinized or denicotinized cigarette in counterbalanced order. Positive affect was assessed before and at two time …

The Programmed Death-1 And Interleukin-10 Pathways Play A Down-Modulatory Role In Lp-Bm5 Retrovirus-Induced Murine Immunodeficiency Syndrome, Kathy A. Green, Taku Okazaki, Tasuku Honjo, W. James Cook, William R. Green

Dartmouth Scholarship

Pathology due to the immune system's response to viral infections often represents a delicate balance between inhibition of viral pathogenesis and regulation of protective immunity. In susceptible C57BL/6 (B6) mice, the murine retroviral isolate LP-BM5 induces splenomegaly, hypergammaglobulinemia, profound B- and T-cell immunodeficiency, and increased susceptibility to opportunistic pathogens and terminal B-cell lymphomas. Here, we report that B6.PD-1 (programmed death-1) and B6.IL-10 knockout mice are substantially more susceptible to LP-BM5-induced disease than wild-type B6 mice. LP-BM5-infected B6.PD-1^−/− mice developed more severe splenomegaly, hypergammaglobulinemia, and immunodeficiency than infected B6 mice: PD-1^−/− mice are more susceptible to lower doses of …

A Developmental Cycle Masks Output From The Circadian Oscillator Under Conditions Of Choline Deficiency In Neurospora, Mi Shi, Luis F. Larrondo, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

In Neurospora, metabolic oscillators coexist with the circadian transcriptional/translational feedback loop governed by the FRQ (Frequency) and WC (White Collar) proteins. One of these, a choline deficiency oscillator (CDO) observed in chol-1 mutants grown under choline starvation, drives an uncompensated long-period developmental cycle ( approximately 60-120 h). To assess possible contributions of this metabolic oscillator to the circadian system, molecular and physiological rhythms were followed in liquid culture under choline starvation, but these only confirmed that an oscillator with a normal circadian period length can run under choline starvation. This finding suggested that long-period developmental cycles elicited by nutritional stress …

Porcine Intestinal Epithelial Cell Lines As A New In Vitro Model For Studying Adherence And Pathogenesis Of Enterotoxigenic Escherichia Coli, Seung Y. Koh, Sajan George, Volker Brozel, Rodney A. Moxley, David H. Francis, Radhey Kaushik

School of Veterinary and Biomedical Sciences: Faculty Publications

Enterotoxigenic Escherichia coli (ETEC) infections result in large economic losses in the swine industry worldwide. The organism causes diarrhea by adhering to and colonizing enterocytes in the small intestines. While much progress has been made in understanding the pathogenesis of ETEC, no homologous intestinal epithelial cultures suitable for studying porcine ETEC pathogenesis have been described prior to this report. In the current study, we investigated the adherence of various porcine ETEC strains to two porcine (IPEC-1 and IPEC-J2) and one human (INT-407) small intestinal epithelial cell lines. Each cell line was assessed for its ability to support the adherence of …

Ada News - 12/10/2007, American Dental Association, Publishing Division

ADA News

Established in 1970 as the official newspaper of the American Dental Association, the ADA News serves practicing dentists and others allied to the dental profession in the U.S. and internationally. It is the No. 1 source of news and information about the many benefits and services the ADA delivers to members daily as well as timely information on scientific, social, political and economic developments affecting dentistry and health care.

Palestinian Health Institutions: Finding A Way Forward In The Wake Of The Second Intifada, Peter E. Hilsenrath, Karan P. Singh

Eberhardt School of Business Faculty Articles

The strength of Hamas in Palestinian elections in early 2006 reshuffled the cards in the game of Middle East politics. Many astonished observers have sought an explanation for this political change. But the election result should not have been so surprising. Hamas has earned a reputation of clean governance and compassion for the poor, unlike the Fatah-led Palestinian Authority. Hamas has had a strong presence in the health sector which helped establish its legitimacy and popularity. This paper reviews bilateral and multilateral aid to Palestinians following the second intifada and argues that not enough was done by the international community …