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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 …

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 …

Voices Raised, Issue 18, University Of Dayton. Women's Center

Women’s Center Newsletter

Included in this issue: Women and Politics; Native American Woman Author comes to UD; Unity Week; Marianist Sisters on Campus; Christmas on Campus Leaders Keeping the Tradition; What is Really Important During the Holidays; Avoiding the Holidays Stress; Rape and personal safety/self-defense.

The Stem Cell Debate Continues: The Buying And Selling Of Eggs For Research, Françoise Baylis, Carolyn Mcleod

Philosophy Publications

Now that stem cell scientists are clamouring for human eggs for cloning-based stem cell research, there is vigorous debate about the ethics of paying women for their eggs. Generally speaking, some claim that women should be paid a fair wage for their reproductive labour or tissues, while others argue against the further commodification of reproductive labour or tissues and worry about voluntariness among potential egg providers. Siding mainly with those who believe that women should be financially compensated for providing eggs for research, the new stem cell guidelines of the International Society for Stem Cell Research (ISSCR) legitimise both reimbursement …

Illusory Predictors: Generalizability Of Findings In Cocaine Treatment Retention Research, Angela L Stotts, Marc E Mooney, Shelly L Sayre, Meredith Novy, Joy M Schmitz, John Grabowski

Faculty, Staff and Student Publications

Treatment retention is of paramount importance in cocaine treatment research as treatment completion rates are often 50% or less. Failure to retain cocaine patients in treatment has both significant research and clinical implications. In this paper we qualitatively and quantitatively demonstrate the inconsistency found across analyses of retention predictors in order to highlight the problem. First, a qualitative review of the published literature was undertaken to identify the frequency of predictors studied and their relations to treatment retention. Second, an empirical demonstration of predictor stability was conducted by testing a common set of variables across three similar 12-week cocaine clinical …

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model., Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J Yasha Kresh, John W.C. Entwistle, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Membranous Dysmenorrhea: A Case Series, Hatim A. Omar, Shawn J. Smith

Pediatrics Faculty Publications

The purpose was to illustrate the variability of hormonal contraception of patients that presented with membranous dysmenorrheal. A case analysis chart review was completed on six patients referred to a Pediatric Gynecologist in an academic setting. In each case the patient underwent a thorough pelvic and bimanual exam. Following the initial presentation, each patient continued to be followed on a regular visits. Cases: Two were using the transdermal contraceptive patch and oral contraceptive, but following the expulsion of decidual cast, they were both placed on depot medroxyprogesterone acetate (DMPA) without further complications. Three of the six cases were on DMPA …

Nonsexual Transmission Of Anogenital Warts In Children: A Retrospective Analysis, Valerie Jones, Shawn J. Smith, Hatim A. Omar

Pediatrics Faculty Publications

The purpose was to evaluate the prevalence of sexual abuse in patients who were referred to a pediatric gynecologist for evaluation based on the clinical findings of anogenital warts. A retrospective analysis was performed on 131 patients between the ages 6 month and 9 years referred to a pediatric gynecologist after the finding of anogenital warts by a clinical provider, parent or caregiver. A complete physical examination under colposcopy by a the same, trained pediatric gynecologist was completed, and a complete medical and family history including maternal and sibling history for evidence of Human Papillomavirus (HPV) and anogenital warts. The …

Adaptive Radiotherapy Planning On Decreasing Gross Tumor Volumes As Seen On Megavoltage Computed Tomography Images., Curtis Woodford, Slav Yartsev, R. Dar, Glenn Bauman, Jacob Van Dyk

Oncology Publications

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV.

METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages …

Donating Fresh Versus Frozen Embryos To Stem Cell Research: In Whose Interests?, Carolyn Mcleod, Françoise Baylis

Philosophy Publications

Some stem cell researchers believe that it is easier to derive human embryonic stem cells from fresh rather than frozen embryos and they have had in vitro fertilization (IVF) clinicians invite their infertility patients to donate their fresh embryos for research use. These embryos include those that are deemed 'suitable for transfer' (i.e. to the woman's uterus) and those deemed unsuitable in this regard. This paper focuses on fresh embryos deemed suitable for transfer - hereafter 'fresh embryos'- which IVF patients have good reason not to donate. We explain why donating them to research is not in the self-interests specifically …

The Activity Of Azithromycin Against Leishmania (Viannia) Braziliensis And Leishmania (Leishmania) Amazonensis In The Golden Hamster Model., Angel Sinagra, Concepción Luna, David Abraham, Maria Del Carmen Iannella, Adelina Riarte, Alejandro J. Krolewiecki

Department of Microbiology and Immunology Faculty Papers

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, …

Dissociating Speech Perception And Comprehension At Reduced Levels Of Awareness, Matthew H Davis, Martin R Coleman, Anthony R Absalom, Jennifer M Rodd, Ingrid Johnsrude, Basil F Matta, Adrian M Owen, David K Menon

Brain and Mind Institute Researchers' Publications

We used functional MRI and the anesthetic agent propofol to assess the relationship among neural responses to speech, successful comprehension, and conscious awareness. Volunteers were scanned while listening to sentences containing ambiguous words, matched sentences without ambiguous words, and signal-correlated noise (SCN). During three scanning sessions, participants were nonsedated (awake), lightly sedated (a slowed response to conversation), and deeply sedated (no conversational response, rousable by loud command). Bilateral temporal-lobe responses for sentences compared with signal-correlated noise were observed at all three levels of sedation, although prefrontal and premotor responses to speech were absent at the deepest level of sedation. Additional …

Human Parietal "Reach Region" Primarily Encodes Intrinsic Visual Direction, Not Extrinsic Movement Direction, In A Visual Motor Dissociation Task., Juan Fernandez-Ruiz, Herbert C Goltz, Joseph F X Desouza, Tutis Vilis, J Douglas Crawford

Brain and Mind Institute Researchers' Publications

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to …

Do Vegetative Patients Retain Aspects Of Language Comprehension? Evidence From Fmri, Martin R Coleman, Jennifer M Rodd, Matthew H Davis, Ingrid Johnsrude, David K Menon, John D Pickard, Adrian M Owen

Brain and Mind Institute Researchers' Publications

A diagnosis of vegetative state is made if a patient demonstrates no evidence of awareness of self or environment, no evidence of sustained, reproducible, purposeful or voluntary behavioural response to sensory stimuli and critically no evidence of language comprehension. For those patients who retain peripheral motor function, rigorous behavioural assessment is usually able to determine retained function. However, some patients do not retain the ability to respond overtly to command and it is becoming increasingly accepted that assessment of these patients should include techniques, which do not rely on any 'motor action' on the part of the patient. Here, we …

Effects Of Atomoxetine On Growth In Children With Attention-Deficit/Hyperactivity Disorder Following Up To Five Years Of Treatment., Thomas J. Spencer, Christopher J. Kratochvil, R. Bart Sangal, Keith E. Saylor, Charles E. Bailey, David W. Dunn, Daniel A. Geller, Charles D. Casat, Robert S. Lipetz, Rakesh Jain, Jeffrey H. Newcorn, Dustin D. Ruff, Peter D. Feldman, Amanda J. Furr, Albert J. Allen

Journal Articles: Psychiatry

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine.

METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years.

RESULTS: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected …

Voices Raised, Issue 17, University Of Dayton. Women's Center

Women’s Center Newsletter

Included in this issue: Loving Your Body From the Inside Out; Out of the Shadows; One-to-One with Sr. Schmeling; Women’s Leadership House Leading Discussion; Date Rape Drugs; Mary’s Presence on Campus is Strengthened; Breast Cancer Awareness Spreads Through Dayton; Stop Hate Week.

Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal

Department of Pediatrics Faculty Papers

Phosphatidylserine (PS)-positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1alpha, TNF-alpha, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface-expressed PS (PSR) similar to that expressed on activated macrophages. …

The Feminisation Of British Neurology: Implications For Workforce Planning., C. B. Carroll, Dsnap Tengah, C. Lawthom, G. Venables

Peninsula Medical School

As in other hospital specialties, an increasing proportion of neurology trainees are female. To predict the workforce implications it is necessary to determine what life choices future neurologists will make. A questionnaire survey of life choices was administered to neurology consultants and trainees, general medical senior house officers, and medical students. Of the 344 respondents, 3% of specialist registrars (SpRs) and 4.6% of consultants work part time. Eighty-seven per cent of female and 22% of male junior doctors plan to work part time for, on average, 7.5 and 1.5 years respectively. Thirty percent of consultants also plan to work part …

Defective Dna Base Excision Repair In Brain From Individuals With Alzheimer's Disease And Amnestic Mild Cognitive Impairment, Lior Weissman, Dong-Gyu Jo, Martin M. Sørensen, Nadja C. De Souza-Pinto, William R. Markesbery, Mark P. Mattson, Vilhelm A. Bohr

Pathology and Laboratory Medicine Faculty Publications

Oxidative stress is thought to play a role in the pathogenesis of Alzheimer's disease (AD) and increased oxidative DNA damage has been observed in brain tissue from AD patients. Base excision repair (BER) is the primary DNA repair pathway for small base modifications such as alkylation, deamination and oxidation. In this study, we have investigated alterations in the BER capacity in brains of AD patients. We employed a set of functional assays to measure BER activities in brain tissue from short post-mortem interval autopsies of 10 sporadic AD patients and 10 age-matched controls. BER activities were also measured in brain …

Polymorphisms In Nucleotide Excision Repair Genes, Arsenic Exposure, And Non-Melanoma Skin Cancer In New Hampshire, Katie M. Applebaum, Margaret R. Karagas, David J. Hunter, Paul J. Catalano, Steven H. Byler, Steve Morris, Heather H. Nelson

Dartmouth Scholarship

Background:

Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC).

Objective:

We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC.

Methods:

Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail …

Comeback Of Appalachian Female Stroke Survivors: The Interrelationships Of Cognition, Function, Self-Concept, Interpersonal, And Social Relationships., Patricia Mckenzie Vanhook

Electronic Theses and Dissertations

The purpose of this descriptive correlational study was to examine the comeback phase of the Trajectory of Chronic Illness Management for Appalachian women stroke survivors. This study predicted comeback as a relationship between physical healing, biographical reengagement, and psychological coming to terms that was mediated by rehabilitation.

The concepts were evaluated through investigation of function and cognitive abilities, self-assessment of recovery, health rating, ability to control life, relationship changes, physical and mental health, and limitations of activities due to poor physical or mental health. Data were collected using, the Stroke Impact Scale (3.0) (Duncan, Bode, Lia, & Perera, 2003), the …

Left Ventricular Noncompaction Mimicking Peripartum Cardiomyopathy., Chetan Patel, Girish S. Shirali, Naveen Pereira

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Chronic Administration Of R-Flurbiprofen Attenuates Learning Impairments In Transgenic Amyloid Precursor Protein Mice, Thomas Kukar, Sonya Prescott, Jason L. Eriksen, Vallie Holloway, M. Paul Murphy, Edward H. Koo, Todd E. Golde, Michelle M. Nicolle

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Abeta42 in cell culture and animal models, and that the effect of NSAIDs on Abeta42 is independent of the inhibition of cyclooxygenase by these compounds. Since Abeta42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Abeta42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Abeta42 lowering agent with greatly reduced cyclooxygenase activity that …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model, Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J. Yasha Kresh, John W.C. Entwhistle Iii, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Regulation Of Meiotic Cohesion And Chromosome Core Morphogenesis During Pachytene In Drosophila Oocytes, Radhika S. Khetani, Sharon E. Bickel

Dartmouth Scholarship

During meiosis, cohesion between sister chromatids is required for normal levels of homologous recombination, maintenance of chiasmata and accurate chromosome segregation during both divisions. In Drosophila, null mutations in the ord gene abolish meiotic cohesion, although how ORD protein promotes cohesion has remained elusive. We show that SMC subunits of the cohesin complex colocalize with ORD at centromeres of ovarian germ-line cells. In addition, cohesin SMCs and ORD are visible along the length of meiotic chromosomes during pachytene and remain associated with chromosome cores following DNase I digestion. In flies lacking ORD activity, cohesin SMCs fail to accumulate at oocyte …

Let-7 Expression Defines Two Differentiation Stages Of Cancer, Scott Shell, Sun-Mi Park, Amir Reza Radjabi, Robert Schickel, Emily Kistner, David Jewell

Dartmouth Scholarship

The early phases of carcinogenesis resemble embryonic development, often involving the reexpression of embryonic mesenchymal genes. The NCI60 panel of human tumor cell lines can genetically be subdivided into two superclusters (SCs) that correspond to CD95 Type I and II cells. SC1 cells are characterized by a mesenchymal and SC2 cells by an epithelial gene signature, suggesting that SC1 cells represent less differentiated, advanced stages of cancer. miRNAs are small 20- to 22-nucleotide-long noncoding RNAs that inhibit gene expression at the posttranscriptional level. By performing miRNA expression analysis on 10 Type I and 10 Type II cells, we have determined …

Walking Age Does Not Explain Term Versus Preterm Difference In Bone Geometry, Haifa Abou Samra, Bonny Specker

Ethel Austin Martin Program Publications

OBJECTIVE: To elucidate the relationship between bone geometry and onset of walking in former term and preterm children.
STUDY DESIGN: We conducted a cross-sectional study of 128 preschool children aged 3 to 5 years who underwent peripheral quantitative computerized tomography measures of bone size at the distal tibia. Linear models were developed, stratifying by sex, to determine whether bone differences between children born term and preterm were caused by differences in walking age.
RESULTS: Children with a history of preterm birth walked later than children born at term (12.4 +/- 0.5 versus 10.9 +/- 0.2 months; P = .004); however, …

Pp2cdelta (Ppm1d, Wip1), An Endogenous Inhibitor Of P38 Mapk, Is Regulated Along With Trp53 And Cdkn2a Following P38 Mapk Inhibition During Mouse Preimplantation Development., Jenny A Hickson, Barry Fong, Patricia H Watson, Andrew J Watson

Obstetrics & Gynaecology Publications

Preimplantation embryos utilize mitogen-activated protein kinase signaling (MAPK) pathways to relay signals from the external environment to prepare appropriate responses and adaptations to a changing milieu. It is therefore important to investigate how MAPK pathways are regulated during preimplantation development. This study was conducted to investigate whether PP2Cdelta (Ppm1d, WIP1) is expressed during mouse preimplantation development and to determine the influences of p38 MAPK inhibition on expression of Trp53 (p53), Ppm1d, (WIP1), and Cdkn2a (p16) during mouse preimplantation development. Our results indicate that Trp53, Ppm1d, and Cdkn2a mRNAs and TRP53 and PP2Cdelta proteins are expressed throughout mouse preimplantation development. Treatment …

Spontaneous Low-Frequency Fluctuations In The Bold Signal In Schizophrenic Patients: Anomalies In The Default Network, Robyn L Bluhm, Jodi Miller, Ruth A Lanius, Elizabeth A Osuch, Kristine Boksman, R W J Neufeld, Jean Theberge, Betsy Schaefer, Peter Williamson

Department of Medicine Publications

Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable …