Digital Commons Network^™

Novel Napi-Iic Mutations Causing Hhrh And Idiopathic Hypercalciuria In Several Unrelated Families: Long-Term Follow-Up In One Kindred., Y Yu, S R. Sanderson, M Reyes, A Sharma, N Dunbar, Tarak Srivastava, H Jüppner, C Bergwitz

Manuscripts, Articles, Book Chapters and Other Papers

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous …

Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND AIMS: Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.

METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.

RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls …

Nitrous Oxide Myelopathy Posing As Spinal Cord Injury., George M. Ghobrial, Md, Richard Dalyai, Md, Adam Flanders, Md, James Harrop, Md

Department of Neurosurgery Faculty Papers

The authors describe a patient who presented with acute tetraparesis and a proposed acute traumatic spinal cord injury that was the result of nitrous oxide myelopathy. This 19-year-old man sustained a traumatic fall off a 6-ft high wall. His examination was consistent with a central cord syndrome with the addition of dorsal column impairment. Cervical MRI demonstrated an isolated dorsal column signal that was suggestive of a nontraumatic etiology. The patient's symptoms resolved entirely over the course of 48 hours. Nitrous oxide abuse is increasing in prevalence. Its toxic side effects can mask vitamin B12 and folate deficiency and central …

Arsenic, Organic Foods, And Brown Rice Syrup, Brian P. Jackson, Vivien F. Taylor, Margaret R. Karagas, Tracy Punshon, Kathryn L. Cottingham

Dartmouth Scholarship

Background: Rice can be a major source of inorganic arsenic (As_i) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products.

Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes.

Methods: We used …

Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass.

METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean …

Adult Ecmo And Gastrointestinal Bleeding From Small Bowel Arteriovenous Malformations: A Novel Treatment Using Spiral Enteroscopy., Konrad Sarosiek, Hitoshi Hirose, Harrison T Pitcher, Nicholas C. Cavarocchi

Department of Surgery Faculty Papers

Hemorrhagic complications on extracorporeal membrane oxygenation (ECMO) are common because of the need for anticoagulation to maintain the oxygenator and circuitry. Gastrointestinal bleeding (GIB) is reported to occur in 3-6% of ECMO patients, ¹ requiring frequent transfusions as well as multiple diagnostic and therapeutic interventions. Multiple transfusions can result in volume overload, coagulopathies and infections leading to significant morbidity and mortality. We present the first published case of GIB from an arteriovenous malformation (AVM) treated with a novel therapy termed spiral enteroscopy while the patient remained on venoarterial (VA) ECMO.

A Two-Stage Cluster Sampling Method Using Gridded Population Data, A Gis, And Google Earth(Tm) Imagery In A Population-Based Mortality Survey In Iraq, Lp Galway, Nathaniel Bell, Al Shatari Sae, Amy Hagopian, Gilbert Burnham, Abraham Flaxman, Wiliam M. Weiss, Julie Rajaratnam, Tim K. Takaro

Faculty Publications

BACKGROUND:

Mortality estimates can measure and monitor the impacts of conflict on a population, guide humanitarian efforts, and help to better understand the public health impacts of conflict. Vital statistics registration and surveillance systems are rarely functional in conflict settings, posing a challenge of estimating mortality using retrospective population-based surveys.

RESULTS:

We present a two-stage cluster sampling method for application in population-based mortality surveys. The sampling method utilizes gridded population data and a geographic information system (GIS) to select clusters in the first sampling stage and Google Earth TM imagery and sampling grids to select households in the second sampling …

Nicotine, Ifn-Γ And Retinoic Acid Mediated Induction Of Muc4 In Pancreatic Cancer Requires E2f1 And Stat-1 Transcription Factors And Utilize Different Signaling Cascades., Sateesh Kunigal, Moorthy P. Ponnusamy, Navneet Momi, Surinder K. Batra, Srikumar P. Chellappan

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: The membrane-bound mucins are thought to play an important biological role in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce …

Uterine Epithelial Cells Specifically Induce Interferon-Stimulated Genes In Response To Polyinosinic-Polycytidylic Acid Independently Of Estradiol, Mickey V. Patel, Mimi Ghosh, John V. Fahey, Charles R. Wira

Dartmouth Scholarship

Interferon β (IFNβ) is an antiviral cytokine secreted in response to pathogenic exposure that creates a restrictive intracellular environment through the action of downstream interferon-stimulated genes (ISG). The objective of this study was to examine the expression of IFNβ and ISG in both human uterine epithelial cells (UEC) and the ECC-1 uterine epithelial cell line and determine if expression changes with TLR stimulation and hormone exposure. Stimulation of primary uterine epithelial cells and ECC-1 cells with the TLR3 agonist poly (I∶C) induced the mRNA expression of IFNβ, MxA, OAS2 and PKR. Other TLR agonists including imiquimod and CpG had no …

Spirituality As A Positive Youth Development Construct: A Conceptual Review, Daniel T. L. Shek

Pediatrics Faculty Publications

The concept of spirituality as a positive youth development construct is reviewed in this paper. Both broad and narrow definitions of spirituality are examined and a working definition of spirituality is proposed. Regarding theories of spirituality, different models pertinent to spiritual development and the relationship between spirituality and positive youth development are highlighted. Different ecological factors, particularly family and peer influences, were found to influence spirituality. Research on the influence of spirituality on adolescent developmental outcomes is examined. Finally, ways to promote adolescent spirituality are discussed.

Beliefs In The Future As A Positive Youth Development Construct: A Conceptual Review, Rachel C. F. Sun, Daniel T. L. Shek

Pediatrics Faculty Publications

Beliefs in the future are an internalization of hope and optimism about future outcomes. This paper reviews and compares several theories of hope and optimism and highlights the features constituting beliefs in the future. This paper points out that beliefs in the future include a series of goal-directed thoughts and motivation, such as setting up valued and attainable goals, planning pathways, and maintaining self-confidence and mastery, so as to keep adolescents engaged in the pursuit of goals. This kind of personal mastery, together with sociocultural values, family, school, and peers are the antecedents leading to beliefs in the future, which …

Impact Of The Project P.A.T.H.S. In The Junior Secondary School Years: Objective Outcome Evaluation Based On Eight Waves Of Longitudinal Data, Daniel T. L. Shek, Cecilia M. S. Ma

Pediatrics Faculty Publications

To assess the effectiveness of the Tier 1 Program of the Project P.A.T.H.S., a randomized group trial with eight waves of data collected was carried out. At the fifth year of data collection, 19 experimental schools (n = 2, 662 students) and 24 control schools (n = 3, 272 students) participated in the study. Analyses based on individual growth curve modeling showed that participants in the experimental schools displayed better positive youth development than did participants in the control schools in terms of different indicators derived from the Chinese Positive Youth Development Scale, including moral competence and behavioral competence and …

Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …

Paramyxovirus Fusion And Entry: Multiple Paths To A Common End, Andres Chang, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

The paramyxovirus family contains many common human pathogenic viruses, including measles, mumps, the parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and the zoonotic henipaviruses, Hendra and Nipah. While the expression of a type 1 fusion protein and a type 2 attachment protein is common to all paramyxoviruses, there is considerable variation in viral attachment, the activation and triggering of the fusion protein, and the process of viral entry. In this review, we discuss recent advances in the understanding of paramyxovirus F protein-mediated membrane fusion, an essential process in viral infectivity. We also review the role of the other surface glycoproteins …

Personal Construction Of Cough Medicine Among Young Substance Abusers In Hong Kong, Daniel T. L. Shek

Pediatrics Faculty Publications

Although cough medicine abuse is a growing problem in many places, there is no study examining the views of young substance abusers toward cough medicine. The objective of this study was to examine personal constructions of cough medicine abusers via the repertory grid tests (N = 11). Several observations are highlighted from the study. First, personal constructions of cough medicine were mixed, including the benefits and harmful effects of its abuse. Second, although the informants perceived cough medicine to be addictive and harmful, they perceived cough medicine to be less addictive and less harmful than did heroin. Third, while the …

Evaluation Of The Project P.A.T.H.S. Based On Students' Weekly Diaries: Findings From Eight Datasets, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

This paper aims to investigate the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. (positive adolescent training through holistic social programmes) based on eight datasets collected between 2005 and 2009. A total of 1,138 students who participated in the program were randomly invited (from the whole grade or in some classes) to write a piece of journal in the form of a weekly diary in order to reveal their perceptions and feelings regarding the program and the perceived benefits of the program. Based on an integration of findings from different databases, results showed that the respondents generally (1) …

Evaluation Of A Positive Youth Development Program Based On The Repertory Grid Test, Daniel T. L. Shek

Pediatrics Faculty Publications

The repertory grid test, based on personal construct psychology, was used to evaluate the effectiveness of Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong. One hundred and four program participants (n = 104) were randomly invited to complete a repertory grid based on personal construct theory in order to provide both quantitative and qualitative data for measuring self-identity changes after joining the program. Findings generally showed that the participants perceived that they understood themselves better and had stronger resilience after joining the program. Participants also saw themselves as closer to their ideal selves and other positive …

Realist Synthesis: Illustrating The Method For Implementation Research., Jo Rycroft-Malone, Brendan Mccormack, Alison M. Hutchinson, Kara Decorby, Tracey K. Bucknall, Bridie Kent, Alyce Schultz, Erna Snelgrove-Clarke, Cheryl B. Stetler, Marita Titler, Lars Wallin, Val Wilson

School of Nursing and Midwifery

BACKGROUND: Realist synthesis is an increasingly popular approach to the review and synthesis of evidence, which focuses on understanding the mechanisms by which an intervention works (or not). There are few published examples of realist synthesis. This paper therefore fills a gap by describing, in detail, the process used for a realist review and synthesis to answer the question 'what interventions and strategies are effective in enabling evidence-informed healthcare?' The strengths and challenges of conducting realist review are also considered. METHODS: The realist approach involves identifying underlying causal mechanisms and exploring how they work under what conditions. The stages of …

Obstructive Sleep Apnea Syndrome And Perioperative Complications: A Systematic Review Of The Literature., Tajender S. Vasu, Md, Ms, Ritu G. Grewal, Md, Karl Doghramji, Md

Department of Sleep Medicine Faculty Papers

Obstructive sleep apnea syndrome (OSAS) is a common sleep related breathing disorder. Its prevalence is estimated to be between 2% and 25% in the general population. However, the prevalence of sleep apnea is much higher in patients undergoing elective surgery. Sedation and anesthesia have been shown to increase the upper airway collapsibility and therefore increasing the risk of having postoperative complications in these patients. Furthermore, the majority of patients with sleep apnea are undiagnosed and therefore are at risk during the perioperative period. It is important to identify these patients so that appropriate actions can be taken in a timely …

Qualitative Evaluation Of The Project P.A.T.H.S.: An Integration Of Findings Based On Program Implementers, Daniel T. L. Shek

Pediatrics Faculty Publications

An integration of the qualitative evaluation findings collected from program implementers conducting the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in different years (n = 177 participants in 36 focus groups) was carried out. General qualitative data analyses utilizing intra and interrater reliability techniques were performed. Results showed that the descriptors used to describe the program and the metaphors named by the informants that could stand for the program were generally positive in nature. Program participants also perceived the program to be beneficial to the development of the students in different psychosocial domains. The present study further supports …

Retinoids Regulate The Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Linda Kelsey, Parul Katoch, Kristen E. Johnson, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The retinoids, the natural or synthetic derivatives of Vitamin A (retinol), are essential for the normal development of prostate and have been shown to modulate prostate cancer progression in vivo as well as to modulate growth of several prostate cancer cell lines. 9-cis-retinoic acid and all-trans-retinoic acid are the two most important metabolites of retinol. Gap junctions, formed of proteins called connexins, are ensembles of intercellular channels that permit the exchange of small growth regulatory molecules between adjoining cells. Gap junctional communication is instrumental in the control of cell growth. We examined the effect of 9-cis-retinoic acid and all-trans retinoic …

Prostate Cancer-Specific And Potent Antitumor Effect Of A Dd3-Controlled Oncolytic Virus Harboring The Pten Gene, Miao Ding, Xin Cao, Hai-Neng Xu, Jun-Kai Fan, Hong-Ling Huang, Dong-Qin Yang, Yu-Hua Li, Jian Wang, Runsheng Li, Xin-Yuan Liu

Molecular and Cellular Biochemistry Faculty Publications

Prostate cancer is a major health problem for men in Western societies. Here we report a Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa), in which PTEN was inserted into a DD3-controlled oncolytic viral vector (OV) to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) or, briefly, Ad.DD3.D55-PTEN. The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence, resulting in much higher expression of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN …

Genetics Of Clusterin Isoform Expression And Alzheimer's Disease Risk, I-Fang Ling, Jiraganya Bhongsatiern, James F. Simpson, David W. Fardo, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted …

Adjunct Primer For The Use Of National Comprehensive Cancer Network Guidelines For The Surgical Management Of Cutaneous Malignant Melanoma Patients., Edibaldo Silva

Journal Articles: Oncology and Hematology

Recently, a Surveillance Epidemiology and End Results (SEER) survey of melanoma patterns of care by the Mayo Clinic, Scottsdale showed remarkable deviations from best practice patterns throughout the country. The study, which analyzed the SEER records of 35,126 stage I to III cutaneous malignant melanoma patients treated from 2004 to 2006, showed that adherence to National Comprehensive Cancer Network (NCCN) therapeutic resection margins occurred in less than 36% of patients. Similarly, considerable variation in the quality of melanoma care in the United States when assessed using 26 quality indicators drawn by a panel of melanoma experts was independently reported. These …

Genetic Association Studies Of Copy-Number Variation: Should Assignment Of Copy Number States Precede Testing?, Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei Wang, Brooke L. Fridley

Biostatistics Faculty Publications

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array …

Pilates Based Core Stability Training In Ambulant Individuals With Multiple Sclerosis: Protocol For A Multi-Centre Randomised Controlled Trial., Jennifer Freeman, Esther Fox, Margaret Gear, Alan Hough

School of Health Professions

BACKGROUND: People with Multiple Sclerosis (MS) frequently experience balance and mobility impairments, including reduced trunk stability. Pilates-based core stability training, which is aimed at improving control of the body's stabilising muscles, is popular as a form of exercise with people with MS and therapists. A replicated single case series study facilitated by the Therapists in MS Group in the United Kingdom (UK) provides preliminary evidence that this approach can improve balance and mobility in ambulant people with MS; further evidence is needed to substantiate these findings to ensure that limited time, energy, finances and resources are used to best effect.This …

Encoding Of Sensory Prediction Errors In The Human Cerebellum., John Schlerf, Richard B Ivry, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two types of errors. Participants made fast out-and-back reaching movements, aiming either for an object that delivered a force pulse if intersected or for a gap between two objects, either of which …

A Heuristic Solution Of The Identifiability Problem Of The Age-Period-Cohort Analysis Of Cancer Occurrence: Lung Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

BACKGROUND: The Age-Period-Cohort (APC) analysis is aimed at estimating the following effects on disease incidence: (i) the age of the subject at the time of disease diagnosis; (ii) the time period, when the disease occurred; and (iii) the date of birth of the subject. These effects can help in evaluating the biological events leading to the disease, in estimating the influence of distinct risk factors on disease occurrence, and in the development of new strategies for disease prevention and treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel approach for estimating the APC effects on disease incidence rates in the frame of …

Positive Youth Development Constructs: Conceptual Review And Application, Daniel T. L. Shek, Rachel C. F. Sun, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Chromosomal Instability And Cancer: A Complex Relationship With Therapeutic Potential, Samuel F. Bakhoum, Duane A. Compton

Dartmouth Scholarship

Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive. It is now evident that the role of CIN in tumor initiation and growth is more complex than previously thought. Furthermore, distinguishing CIN, which consists of elevated rates of chromosome missegregation, from aneuploidy, which is a state of abnormal chromosome number, is crucial to understanding their respective contributions in cancer. Collectively, experimental evidence suggests that CIN enables tumor adaptation by allowing tumors to constantly sample the aneuploid fitness landscape. This complex relationship, together with …