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Identifying Genetic Variants For Heart Rate Variability In The Acetylcholine Pathway, Harriëtte Riese, Loretto M. Muñoz, Catharina A. Hartman, Xiuhua Ding, Shaoyong Su, Albertine J. Oldehinkel, Arie M. Van Roon, Peter J. Van Der Most, Joop Lefrandt, Ron T. Gansevoort, Pim Van Der Harst, Niek Verweij, Carmilla M. M. Licht, Dorret I. Boomsma, Jouke-Jan Hottenga, Gonneke Willemsen, Brenda W. J. H. Penninx, Ilja M. Nolte, Eco J. C. De Geus, Xiaoling Wang, Harold Snieder Nov 2014

Identifying Genetic Variants For Heart Rate Variability In The Acetylcholine Pathway, Harriëtte Riese, Loretto M. Muñoz, Catharina A. Hartman, Xiuhua Ding, Shaoyong Su, Albertine J. Oldehinkel, Arie M. Van Roon, Peter J. Van Der Most, Joop Lefrandt, Ron T. Gansevoort, Pim Van Der Harst, Niek Verweij, Carmilla M. M. Licht, Dorret I. Boomsma, Jouke-Jan Hottenga, Gonneke Willemsen, Brenda W. J. H. Penninx, Ilja M. Nolte, Eco J. C. De Geus, Xiaoling Wang, Harold Snieder

Biostatistics Faculty Publications

Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a …


Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero Nov 2014

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …


Multiple Functional Risk Variants In A Smad7 Enhancer Implicate A Colorectal Cancer Risk Haplotype, Barbara K. Fortini, Stephanie Tring, Sarah J. Plummer, Christopher K. Edlund, Victor Moreno, Robert S. Bresalier, Elizabeth L. Barry, Timothy R. Church, Jane C. Figueiredo, Graham Casey Nov 2014

Multiple Functional Risk Variants In A Smad7 Enhancer Implicate A Colorectal Cancer Risk Haplotype, Barbara K. Fortini, Stephanie Tring, Sarah J. Plummer, Christopher K. Edlund, Victor Moreno, Robert S. Bresalier, Elizabeth L. Barry, Timothy R. Church, Jane C. Figueiredo, Graham Casey

Dartmouth Scholarship

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the identification of a number of common variants associated with modest risk. Several risk variants map within the vicinity of TGFβ/BMP signaling pathway genes, including rs4939827 within an intron of SMAD7 at 18q21.1. A previous study implicated a novel SNP (novel 1 or rs58920878) as a functional variant within an enhancer element in SMAD7 intron 4. In this study, we show that four SNPs including novel 1 (rs6507874, rs6507875, rs8085824, and rs58920878) in linkage disequilibrium (LD) with the index SNP rs4939827 demonstrate allele-specific enhancer effects in a large, multi-component …


Impact Of Implementing Performance-Based Financing On Childhood Malnutrition In Rwanda, Agnes Binagwaho, Jeanine Condo, Claire Wagner, Fidele Ngabo, Corine Karema, Steve Kanters, Jamie I. Forrest, Jean De Dieu Bizimana Nov 2014

Impact Of Implementing Performance-Based Financing On Childhood Malnutrition In Rwanda, Agnes Binagwaho, Jeanine Condo, Claire Wagner, Fidele Ngabo, Corine Karema, Steve Kanters, Jamie I. Forrest, Jean De Dieu Bizimana

Dartmouth Scholarship

Background: Malnutrition remains a serious concern in Rwanda, particularly among children under-5 years. Performance-based financing (PBF), an innovative health systems financing strategy, has been implemented at the national level since 2008. This study aimed to assess the impact of PBF and other factors associated with the prevalence of three classifications of malnutrition (stunting, wasting and underweight) in children under-5 years in Rwanda. Methods: The study is a cross-sectional study comprising of 713 children under five years old from 557 households, whose anthropometric measurements (height, weight and age) had been obtained as part of the 2008 Rwanda General Health and HIV …


Subspecialty Surveillance Of Long-Term Course Of Small And Moderate Muscular Ventricular Septal Defect: Heterogenous Practices, Low Yield., Erik L. Frandsen, Aswathy V. House, Yunbin Xiao, David A. Danford, Shelby Kutty Nov 2014

Subspecialty Surveillance Of Long-Term Course Of Small And Moderate Muscular Ventricular Septal Defect: Heterogenous Practices, Low Yield., Erik L. Frandsen, Aswathy V. House, Yunbin Xiao, David A. Danford, Shelby Kutty

Journal Articles: Pediatrics

BACKGROUND: No expert consensus guides practice for intensity of ongoing pediatric cardiology surveillance of hemodynamically insignificant small and moderate muscular ventricular septal defect (mVSD). Therefore, despite the well-established benign natural history of mVSD, there is potential for widely divergent follow up practices. The purpose of this investigation was to evaluate (1) variations in follow up of mVSD within an academic children's hospital based pediatric cardiology practice, and (2) the frequency of active medical or surgical management resulting from follow up of mVSD.

METHODS: We retrospectively reviewed records of 600 patients with isolated mVSD echocardiographically diagnosed between 2006 and 2012. Large …


New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: Understanding Differences And Similarities., Paul P. Dobesh, John Fanikos Nov 2014

New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: Understanding Differences And Similarities., Paul P. Dobesh, John Fanikos

Journal Articles: Pharmacy Practice

Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These …


Method For Investigating Nursing Behaviors Related To Isolation Care., Elizabeth L. Beam, Shawn G. Gibbs, Angela L. Hewlett, Peter C. Iwen, Suzanne L. Nuss, Philip W. Smith Nov 2014

Method For Investigating Nursing Behaviors Related To Isolation Care., Elizabeth L. Beam, Shawn G. Gibbs, Angela L. Hewlett, Peter C. Iwen, Suzanne L. Nuss, Philip W. Smith

Journal Articles: College of Nursing

BACKGROUND: Although an emphasis has been placed on protecting patients by improving health care worker compliance with infection control techniques, challenges associated with patient isolation do exist. To address these issues, a more consistent mechanism to evaluate specific clinical behaviors safely is needed.

METHODS: The research method described in this study used a high fidelity simulation using a live standardized patient recorded by small cameras. Immediately after the simulation experience, nurses were asked to view and comment on their performance. A demographic survey and a video recorded physical evaluation provided participant description. A questionnaire component 1 month after the simulation …


Developmental Differences In The Influence Of Phonological Similarity On Spoken Word Processing In Mandarin Chinese., Jeffrey G Malins, Danqi Gao, Ran Tao, James R Booth, Hua Shu, Marc F Joanisse, Li Liu, Amy S Desroches Nov 2014

Developmental Differences In The Influence Of Phonological Similarity On Spoken Word Processing In Mandarin Chinese., Jeffrey G Malins, Danqi Gao, Ran Tao, James R Booth, Hua Shu, Marc F Joanisse, Li Liu, Amy S Desroches

Brain and Mind Institute Researchers' Publications

The developmental trajectory of spoken word recognition has been well established in Indo-European languages, but to date remains poorly characterized in Mandarin Chinese. In this study, typically developing children (N=17; mean age 10; 5) and adults (N=17; mean age 24) performed a picture-word matching task in Mandarin while we recorded ERPs. Mismatches diverged from expectations in different components of the Mandarin syllable; namely, word-initial phonemes, word-final phonemes, and tone. By comparing responses to different mismatch types, we uncovered evidence suggesting that both children and adults process words incrementally. However, we also observed key developmental differences in how subjects treated onset …


Striatum In Stimulus-Response Learning Via Feedback And In Decision Making., Nole M Hiebert, Andrew Vo, Adam Hampshire, Adrian M Owen, Ken N Seergobin, Penny A Macdonald Nov 2014

Striatum In Stimulus-Response Learning Via Feedback And In Decision Making., Nole M Hiebert, Andrew Vo, Adam Hampshire, Adrian M Owen, Ken N Seergobin, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

Cognitive deficits are recognized in Parkinson's disease. Understanding cognitive functions mediated by the striatum can clarify some of these impairments and inform treatment strategies. The dorsal striatum, a region impaired in Parkinson's disease, has been implicated in stimulus-response learning. However, most investigations combine acquisition of associations between stimuli, responses, or outcomes (i.e., learning) and expression of learning through response selection and decision enactment, confounding these separate processes. Using neuroimaging, we provide evidence that dorsal striatum does not mediate stimulus-response learning from feedback but rather underlies decision making once associations between stimuli and responses are learned. In the experiment, 11 males …


Use Of Social Media In Dental Schools: Pluses, Perils, And Pitfalls From A Legal Perspective, Joseph W. Parkinson, Sharon P. Turner Nov 2014

Use Of Social Media In Dental Schools: Pluses, Perils, And Pitfalls From A Legal Perspective, Joseph W. Parkinson, Sharon P. Turner

Oral Health Practice Faculty Publications

One of the ways dental education is changing the way it is preparing the next generation of learners is through efficient utilization of interactive social media. Social media, which facilitates interaction and sharing of new ideas, is being utilized to educate students, residents, and faculty. Unfortunately, as with most improvements in technology, there are growing pains. Faculty, student, and patient interaction on social media platforms, such as Facebook and Twitter, can lead to inappropriate or embarrassing situations. Striking the appropriate balance between free speech rights of students and faculty and the need for colleges and universities to have efficient operations …


Pharmacokinetic And Pharmacodynamic Interactions Between Antiepileptics And Antidepressants, Domenico Italiano, Edoardo Spina, Jose De Leon Nov 2014

Pharmacokinetic And Pharmacodynamic Interactions Between Antiepileptics And Antidepressants, Domenico Italiano, Edoardo Spina, Jose De Leon

Psychiatry Faculty Publications

INTRODUCTION: Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant.

AREAS COVERED: This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed.

EXPERT OPINION: The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided …


Technical Performance Score Is Associated With Outcomes After The Norwood Procedure., Meena Nathan, Lynn A. Sleeper, Richard G. Ohye, Peter C. Frommelt, Christopher A. Caldarone, James S. Tweddell, Minmin Lu, Gail D. Pearson, J William Gaynor, Christian Pizarro, Ismee A. Williams, Steven D. Colan, Carolyn Dunbar-Masterson, Peter J. Gruber, Kevin Hill, Jennifer Hirsch-Romano, Jeffrey P. Jacobs, Jonathan R. Kaltman, S Ram Kumar, David Morales, Scott M. Bradley, Kirk Kanter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali Nov 2014

Technical Performance Score Is Associated With Outcomes After The Norwood Procedure., Meena Nathan, Lynn A. Sleeper, Richard G. Ohye, Peter C. Frommelt, Christopher A. Caldarone, James S. Tweddell, Minmin Lu, Gail D. Pearson, J William Gaynor, Christian Pizarro, Ismee A. Williams, Steven D. Colan, Carolyn Dunbar-Masterson, Peter J. Gruber, Kevin Hill, Jennifer Hirsch-Romano, Jeffrey P. Jacobs, Jonathan R. Kaltman, S Ram Kumar, David Morales, Scott M. Bradley, Kirk Kanter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: The technical performance score (TPS) has been reported in a single center study to predict the outcomes after congenital cardiac surgery. We sought to determine the association of the TPS with outcomes in patients undergoing the Norwood procedure in the Single Ventricle Reconstruction trial.

Methods: We calculated the TPS (class 1, optimal; class 2, adequate; class 3, inadequate) according to the predischarge echocardiograms analyzed in a core laboratory and unplanned reinterventions that occurred before discharge from the Norwood hospitalization. Multivariable regression examined the association of the TPS with interval to first extubation, Norwood length of stay, death or transplantation, …


The Significance Of Functional Renal Obstruction In Predicting Pathologic Stage Of Upper Tract Urothelial Carcinoma., Michael J. Amirian, Kushan Radadia, Hadley Narins, Kelly A. Healy, Scott G. Hubosky, Demetrius H. Bagley, Edouard J. Trabulsi, Costas D. Lallas Nov 2014

The Significance Of Functional Renal Obstruction In Predicting Pathologic Stage Of Upper Tract Urothelial Carcinoma., Michael J. Amirian, Kushan Radadia, Hadley Narins, Kelly A. Healy, Scott G. Hubosky, Demetrius H. Bagley, Edouard J. Trabulsi, Costas D. Lallas

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Assessing the severity of upper tract urothelial carcinoma (UTUC) has been difficult because of inadequate biopsy specimens. Additional predictive parameters of disease stage would be useful when deciding a treatment plan; it has been suggested that preoperative hydronephrosis can be a surrogate. We examined the relationship between preoperative ipsilateral renal obstruction identified by imaging with final pathologic stage after nephroureterectomy (NU) for UTUC. We then analyzed those patients with ipsilateral renal obstruction and examined if tumor location is associated with an advanced pathologic stage.

METHODS: Patients who underwent NU for UTUC between the years 2001 to 2013 …


Sofas And Infant Mortality., Lauren R. Rechtman, Jeffrey D. Colvin, Peter S. Blair, Rachel Y. Moon Nov 2014

Sofas And Infant Mortality., Lauren R. Rechtman, Jeffrey D. Colvin, Peter S. Blair, Rachel Y. Moon

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Sleeping on sofas increases the risk of sudden infant death syndrome and other sleep-related deaths. We sought to describe factors associated with infant deaths on sofas.

METHODS: We analyzed data for infant deaths on sofas from 24 states in 2004 to 2012 in the National Center for the Review and Prevention of Child Deaths Case Reporting System database. Demographic and environmental data for deaths on sofas were compared with data for sleep-related infant deaths in other locations, using bivariate and multivariable, multinomial logistic regression analyses.

RESULTS: A total of 1024 deaths on sofas made up 12.9% of sleep-related infant …


Jewish Dermatologists In Nazi Germany., Walter H.C. Burgdorf, Lawrence Charles Parish Nov 2014

Jewish Dermatologists In Nazi Germany., Walter H.C. Burgdorf, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

With the development of medical specialties beginning in the 1860’s, physicians could devote their time to the study of specific organ systems or surgical approaches. Although Jews had been given full rights in the new Germany by 1871, prejudice and other restrictions often precluded hospital and university appointments. Major specialities like internal medicine and surgery were almost closed to Jews, as were obstetrics and gynecology. Dermatology with its heavy emphasis on sexually transmitted diseases evolved into a suitable domain for Jewish physicians almost by default. Even those Jews who converted to Christianity were not spared from discrimination. Paul Gerson Unna …


Local Population Characteristics And Hemoglobin A1c Testing Rates Among Diabetic Medicare Beneficiaries, Laura C. Yasaitis, Thomas Bubolz, Jonathan S. Skinner, Amitabh Chandra Oct 2014

Local Population Characteristics And Hemoglobin A1c Testing Rates Among Diabetic Medicare Beneficiaries, Laura C. Yasaitis, Thomas Bubolz, Jonathan S. Skinner, Amitabh Chandra

Dartmouth Scholarship

Background: Proposed payment reforms in the US healthcare system would hold providers accountable for the care delivered to an assigned patient population. Annual hemoglobin A1c (HbA1c) tests are recommended for all diabetics, but some patient populations may face barriers to high quality healthcare that are beyond providers' control. The magnitude of fine-grained variations in care for diabetic Medicare beneficiaries, and their associations with local population characteristics, are unknown.

Methods: HbA1c tests were recorded for 480,745 diabetic Medicare beneficiaries. Spatial analysis was used to create ZIP code-level estimated testing rates. Associations of testing rates with local population characteristics that are outside …


Human Cytomegalovirus-Encoded Pul7 Is A Novel Ceacam1-Like Molecule Responsible For Promotion Of Angiogenesis., Jason D. Macmaniman, Andrew Meuser, Sara Botto, Patricia P. Smith, Fenyong Liu, Michael A. Jarvis, Jay A. Nelson, Patrizia Caposio Oct 2014

Human Cytomegalovirus-Encoded Pul7 Is A Novel Ceacam1-Like Molecule Responsible For Promotion Of Angiogenesis., Jason D. Macmaniman, Andrew Meuser, Sara Botto, Patricia P. Smith, Fenyong Liu, Michael A. Jarvis, Jay A. Nelson, Patrizia Caposio

School of Biomedical Sciences

UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required …


Burning Pain Secondary To Clozapine Use: A Case Report., Bradley Linton, Rachel Fu, Penny A Macdonald, Hooman Ganjavi Oct 2014

Burning Pain Secondary To Clozapine Use: A Case Report., Bradley Linton, Rachel Fu, Penny A Macdonald, Hooman Ganjavi

Brain and Mind Institute Researchers' Publications

BACKGROUND: The first of the atypical antipsychotics introduced in the 1970s, clozapine remains the most efficacious neuroleptic to this day. However, serious and potentially fatal side effects have necessitated careful regular monitoring among prescribing clinicians. Some adverse effects (e.g. ischaemic bowel) remain under recognized, while newly identified adverse effects continue to be described in the literature.

CASE PRESENTATION: In this report, we describe a healthy 43-year old Caucasian male who experienced onset of a full body deep burning pain several months after the onset of treatment with clozapine. The pain worsened over time, ceased with cessation of treatment, and returned …


Candida Albicans Ethanol Stimulates Pseudomonas Aeruginosa Wspr-Controlled Biofilm Formation As Part Of A Cyclic Relationship Involving Phenazines, Annie I. Chen, Emily F. Dolben, Chinweike Okegbe, Colleen E. Harty, Yuriy Golub, Sandy Thao, Dae Gon Ha, Sven D. Willger, George A. O'Toole, Caroline S. Harwood, Lars E. P Dietrich, Deborah A. Hogan Oct 2014

Candida Albicans Ethanol Stimulates Pseudomonas Aeruginosa Wspr-Controlled Biofilm Formation As Part Of A Cyclic Relationship Involving Phenazines, Annie I. Chen, Emily F. Dolben, Chinweike Okegbe, Colleen E. Harty, Yuriy Golub, Sandy Thao, Dae Gon Ha, Sven D. Willger, George A. O'Toole, Caroline S. Harwood, Lars E. P Dietrich, Deborah A. Hogan

Dartmouth Scholarship

In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF) and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic- di-GMP (c-di-GMP), and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol …


Copy Number Variation In The Horse Genome, Sharmila Ghosh, Zhipeng Qu, Pranab J. Das, Erica Fang, Rytis Juras, E. Gus Cothran, Sue Mcdonell, Daniel G. Kenney, Teri L. Lear, David L. Adelson, Bhanu P. Chowdhary, Terje Raudsepp Oct 2014

Copy Number Variation In The Horse Genome, Sharmila Ghosh, Zhipeng Qu, Pranab J. Das, Erica Fang, Rytis Juras, E. Gus Cothran, Sue Mcdonell, Daniel G. Kenney, Teri L. Lear, David L. Adelson, Bhanu P. Chowdhary, Terje Raudsepp

Maxwell H. Gluck Equine Research Center Faculty Publications

We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse …


Blood Levels Of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, And Interleukin-6 For Changes In Depressive Symptom Severity After Coronary Artery Bypass Grafting: Prospective Cohort Nested Within A Randomized, Controlled Trial, Daniel M. Pearlman, Jeremiah R. R. Brown, Todd A. Mackenzie, Felix Hernandez, Souhel Najjar Oct 2014

Blood Levels Of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, And Interleukin-6 For Changes In Depressive Symptom Severity After Coronary Artery Bypass Grafting: Prospective Cohort Nested Within A Randomized, Controlled Trial, Daniel M. Pearlman, Jeremiah R. R. Brown, Todd A. Mackenzie, Felix Hernandez, Souhel Najjar

Dartmouth Scholarship

Background: Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium- binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.

Methods: Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and …


Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu Oct 2014

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …


Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood Oct 2014

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …


Artesunate Induces Necrotic Cell Death In Schwannoma Cells., R. W. Button, F. Lin, E. Ercolano, J. H. Vincent, B. Hu, C. O. Hanemann, S. Luo Oct 2014

Artesunate Induces Necrotic Cell Death In Schwannoma Cells., R. W. Button, F. Lin, E. Ercolano, J. H. Vincent, B. Hu, C. O. Hanemann, S. Luo

Peninsula Medical School

Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined …


The Cost Of Moving Optimally: Kinematic Path Selection., Dinant A Kistemaker, Jeremy D Wong, Paul L Gribble Oct 2014

The Cost Of Moving Optimally: Kinematic Path Selection., Dinant A Kistemaker, Jeremy D Wong, Paul L Gribble

Brain and Mind Institute Researchers' Publications

It is currently unclear whether the brain plans movement kinematics explicitly or whether movement paths arise implicitly through optimization of a cost function that takes into account control and/or dynamic variables. Several cost functions are proposed in the literature that are very different in nature (e.g., control effort, torque change, and jerk), yet each can predict common movement characteristics. We set out to disentangle predictions of the different variables using a combination of modeling and empirical studies. Subjects performed goal-directed arm movements in a force field (FF) in combination with visual perturbations of seen hand position. This FF was designed …


Visualization-Aided Classification Ensembles Discriminate Lung Adenocarcinoma And Squamous Cell Carcinoma Samples Using Their Gene Expression Profiles, Ao Zhang, Chi Wang, Shiji Wang, Liang Li, Zhongmin Liu, Suyan Tian Oct 2014

Visualization-Aided Classification Ensembles Discriminate Lung Adenocarcinoma And Squamous Cell Carcinoma Samples Using Their Gene Expression Profiles, Ao Zhang, Chi Wang, Shiji Wang, Liang Li, Zhongmin Liu, Suyan Tian

Markey Cancer Center Faculty Publications

INTRODUCTION: The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC), there are two major histological types of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC).

RESULTS: In this paper, we proposed to integrate a visualization method called Radial Coordinate Visualization (Radviz) with a suitable classifier, aiming at discriminating two NSCLC subtypes using patients' gene expression profiles. Our analyses on simulated data and a real microarray dataset show that combining with a classification method, Radviz may play a role in …


Calcium Supplementation Increases Blood Creatinine Concentration In A Randomized Controlled Trial, Elizabeth L. L. Barry, Leila A. A. Mott, Michal L. L. Melamed, Judith R. Rees, Anastasia Ivanova, Robert S. Sandler, Dennis J. Ahnen, Robert S. Bresalier, Robert W. Summers, Roberd M. Bostick, John A. Baron Oct 2014

Calcium Supplementation Increases Blood Creatinine Concentration In A Randomized Controlled Trial, Elizabeth L. L. Barry, Leila A. A. Mott, Michal L. L. Melamed, Judith R. Rees, Anastasia Ivanova, Robert S. Sandler, Dennis J. Ahnen, Robert S. Bresalier, Robert W. Summers, Roberd M. Bostick, John A. Baron

Dartmouth Scholarship

Background: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.

Methods: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N=1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total …


Naturally Occurring Peer Support Through Social Media: The Experiences Of Individuals With Severe Mental Illness Using Youtube, John A. Naslund, Stuart W. Grande, Kelly A. Aschbrenner, Glyn Elwyn Oct 2014

Naturally Occurring Peer Support Through Social Media: The Experiences Of Individuals With Severe Mental Illness Using Youtube, John A. Naslund, Stuart W. Grande, Kelly A. Aschbrenner, Glyn Elwyn

Dartmouth Scholarship

Increasingly, people with diverse health conditions turn to social media to share their illness experiences or seek advice from others with similar health concerns. This unstructured medium may represent a platform on which individuals with severe mental illness naturally provide and receive peer support. Peer support includes a system of mutual giving and receiving where individuals with severe mental illness can offer hope, companionship, and encouragement to others facing similar challenges. In this study we explore the phenomenon of individuals with severe mental illness uploading videos to YouTube, and posting and responding to comments as a form of naturally occurring …


A Case Of Cutaneous Larva Migrans Presenting In A Pregnant Patient., Kasie Kudrewicz, Kylee N Crittenden, Alison Himes Oct 2014

A Case Of Cutaneous Larva Migrans Presenting In A Pregnant Patient., Kasie Kudrewicz, Kylee N Crittenden, Alison Himes

Women’s Health Articles

Cutaneous larva migrans (CLM) is a pruritic dermatitis caused by migration of the animal hookworm larvae into the epidermis. We present a case of CLM in a 31-year-old pregnant woman. The treatment of CLM relies on antihelminthic agents, such as thiabendazole, albendazole, and ivermectin. This case was interesting in that the standard treatment options previously mentioned were contraindicated owing to the patient's pregnancy. Cryotherapy with liquid nitrogen resulted in complete resolution of her lesion and symptoms.


Temporal And Stochastic Control Of Staphylococcus Aureus Biofilm Development., Derek E. Moormeier, Jeffrey L. Bose, Alexander R. Horswill, Kenneth W. Bayles Oct 2014

Temporal And Stochastic Control Of Staphylococcus Aureus Biofilm Development., Derek E. Moormeier, Jeffrey L. Bose, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Biofilm communities contain distinct microniches that result in metabolic heterogeneity and variability in gene expression. Previously, these niches were visualized within Staphylococcus aureus biofilms by observing differential expression of the cid and lrg operons during tower formation. In the present study, we examined early biofilm development and identified two new stages (designated "multiplication" and "exodus") that were associated with changes in matrix composition and a distinct reorganization of the cells as the biofilm matured. The initial attachment and multiplication stages were shown to be protease sensitive but independent of most cell surface-associated proteins. Interestingly, after 6 h of growth, an …