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Full-Text Articles in Medicine and Health Sciences

Carbohydrates And Fungal Toxin Exposure Influence The Vaginal Microbiota, Metabolome, And Reproductive Health Of Women, Stephanie L. Collins Dec 2017

Carbohydrates And Fungal Toxin Exposure Influence The Vaginal Microbiota, Metabolome, And Reproductive Health Of Women, Stephanie L. Collins

Electronic Thesis and Dissertation Repository

The reproductive health of women is influenced by microorganisms and their metabolites, namely those representing the vaginal microbiota and those producing toxins that are ingested. To manipulate the vaginal microbiota toward a health-associated, Lactobacillusdominant state, an approach adopting prebiotic lactulose was taken. Using batch culture, lactulose supported Lactobacillus maintenance and positively altered metabolites, while not disrupting indigenous L. crispatus epithelial adherence. The vagina also harbours abundant glycogen, but initial assumptions that lactobacilli utilize it were incorrect. I have now shown that glycogen selectively stimulates organisms associated with dysbiosis and L. iners in a self-limiting manner. Other compounds such as environmental …


Prostate Cancer Microparticles In Men Undergoing Radical Prostatectomy, Malcolm James Dewar Dec 2017

Prostate Cancer Microparticles In Men Undergoing Radical Prostatectomy, Malcolm James Dewar

Electronic Thesis and Dissertation Repository

Objectives: To determine changes in prostate microparticle (PMP) concentrations in men with prostate cancer (PCa) after digital rectal examination (DRE), after radical prostatectomy (RP), and at follow-up.

Materials and Methods: 22 men were recruited before RP. Four blood specimens were collected – baseline (specimen 1), post-DRE (specimen 2), immediately post-RP (specimen 3), and follow-up (specimen 4). Pre- and post-DRE urine was collected (Specimen A and B respectively). Flow cytometric analysis of biofluids was performed with fluorescent-labeled antibodies against prostate-specific membrane antigen (PSMA) and polysialic acid. Total MP (TMP) and dual positive (PMP) events per µl of plasma or urine were …


Liver X Receptor And Retinoid X Receptor In Cartilage Development And Homeostasis, Man-Ger Sun Dec 2017

Liver X Receptor And Retinoid X Receptor In Cartilage Development And Homeostasis, Man-Ger Sun

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a heterogeneous and multifactorial degenerative disease characterized by cartilage degradation in the joint. Available treatment options target symptoms but do not address the underlying issue of joint tissue degeneration. A better understanding of the molecular mechanisms maintaining cartilage health is essential for developing novel therapeutic strategies. Previous studies have shown the nuclear receptor Liver X Receptor (LXR) to possess protective roles against cartilage breakdown in OA, however the underlying mechanisms behind this process remain unknown. Since LXR regulates transcription by forming obligate heterodimers with another nuclear receptor, the Retinoid X Receptor (RXR), I hypothesized that LXR and …


Proteomic Characterization Of Human Multipotent Stromal Cells Secreted Proteins With Therapeutic Potential For Β-Cell Regeneration, Miljan Kuljanin Dec 2017

Proteomic Characterization Of Human Multipotent Stromal Cells Secreted Proteins With Therapeutic Potential For Β-Cell Regeneration, Miljan Kuljanin

Electronic Thesis and Dissertation Repository

Novel strategies to stimulate the expansion of β-cell mass in situ are warranted for diabetes therapy. Cell-replacement therapies for the treatment of diabetes have become a focal point in recent years. Endogenous regeneration of β-cell mass has been demonstrated using human multipotent stromal cells (hMSC). However, the secretory factors responsible for initiating endogenous regeneration remain unknown. Successful large-scale proteomic applications to address these questions have been limited in part by difficulties in correctly selecting the appropriate methodologies. Thus, the goal of this thesis was a combination of assessing different proteomic workflows to facilitate investigation into hMSC biology, applying these methods …


Crispr Screen For Identification Of Kinases That Mediate Prostate Cancer Cell Invasion, Hamad Aldhafeeri Dec 2017

Crispr Screen For Identification Of Kinases That Mediate Prostate Cancer Cell Invasion, Hamad Aldhafeeri

Electronic Thesis and Dissertation Repository

Metastasis is the primary cause of mortality in cancer patients. Inhibition of proteins that are involved in the regulation of metastasis are expected to suppress metastasis and represent treatment targets. Our focus is on prostate cancer metastasis and we have developed a novel high-throughput means of performing in vitro screens for regulators of prostate cancer metastasis. We propose to use a focused CRISPR library screen that will “knock out” all human kinases to determine which ones are responsible for prostate cancer metastasis. CRISPR is a potent genetic editing tool and was used to silence all kinases in prostate cells (BPH …


Iron Reduction Response And Demographic Differences Between Diabetics And Non-Diabetics With Cardiovascular Disease Entered To A Controlled Clinical Trial, Leo Zacharski, Galina Shamayeva, Bruce Chow Dec 2017

Iron Reduction Response And Demographic Differences Between Diabetics And Non-Diabetics With Cardiovascular Disease Entered To A Controlled Clinical Trial, Leo Zacharski, Galina Shamayeva, Bruce Chow

Dartmouth Scholarship

Iron-catalyzed oxygen free radical-induced oxidative stress mediates the pathogenesis of diabetes and cardiovascular disease (CVD). Diabetics (n=473) and non-diabetics (n=804) with CVD entered to a randomized trial of iron (ferritin) reduction by calibrated phlebotomy (www.clinicaltrials.gov, Identifier NCT00032357) had comparable iron measures at entry but diabetics had greater burden of CVD and comorbidities, lower hemoglobin and hematocrit levels, and higher glucose levels than non-diabetics. Entry iron measures were lower in diabetics on hypoglycemic therapy compared to diabetics untreated previously. Diabetics and non-diabetics had comparable iron measures during follow-up. Loess analysis of paired ferritin and hemoglobin, and paired ferritin and glucose levels …


Ionis Drug Successfully Reduces Toxic Huntington’S Disease Protein, Paving Way For Phase 2 Trial Of Effect On Patients, Kenneth P. Serbin Dec 2017

Ionis Drug Successfully Reduces Toxic Huntington’S Disease Protein, Paving Way For Phase 2 Trial Of Effect On Patients, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo Dec 2017

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.


Safety And Efficacy Of Apremilast Through 104 Weeks In Patients With Moderate To Severe Psoriasis Who Continued On Apremilast Or Switched From Etanercept Treatment: Findings From The Liberate Study., K Reich, M Gooderham, A Bewley, L Green, J Soung, R Petric, J Marcsisin, J Cirulli, R Chen, V Piguet Dec 2017

Safety And Efficacy Of Apremilast Through 104 Weeks In Patients With Moderate To Severe Psoriasis Who Continued On Apremilast Or Switched From Etanercept Treatment: Findings From The Liberate Study., K Reich, M Gooderham, A Bewley, L Green, J Soung, R Petric, J Marcsisin, J Cirulli, R Chen, V Piguet

Dermatology Faculty Publications

Background

Apremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis.

Objective

To evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial.

Methods

Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and …


Vista Deficiency Attenuates Antibody-Induced Arthritis And Alters Macrophage Gene Expression In Response To Simulated Immune Complexes, Sabrina Ceeraz, Susan K. Eszterhas, Petra Sergent, David A. Armstrong, Alix Ashare, Thomas Broughton, Li Wang, Dov Pechenick, Christopher M. Burns, Randolph J. Noelle, Matthew P. Vincenti, Roy A. Fava Dec 2017

Vista Deficiency Attenuates Antibody-Induced Arthritis And Alters Macrophage Gene Expression In Response To Simulated Immune Complexes, Sabrina Ceeraz, Susan K. Eszterhas, Petra Sergent, David A. Armstrong, Alix Ashare, Thomas Broughton, Li Wang, Dov Pechenick, Christopher M. Burns, Randolph J. Noelle, Matthew P. Vincenti, Roy A. Fava

Dartmouth Scholarship

In addition to activated T cells, the immune checkpoint inhibitor “V domain-containing Ig suppressor of T-cell activation” (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated. Methods: VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis. The collagen antibody-induced arthritis model (CAIA) was performed with DBA/1 J mice treated with antibodies against VISTA and with VISTA-deficient mice (V-KO). Total mRNA from arthritic joints, spleens, and …


Ran Translation At C9orf72-Associated Repeat Expansions Is Selectively Enhanced By The Integrated Stress Response, Katelyn M. Green, M. Rebecca Glineburg, Michael G. Kearse, Brittany N. Flores, Alexander E. Linsalata, Stephen J. Fedak, Aaron C. Goldstrohm, Sami J. Barmada, Peter K. Todd Dec 2017

Ran Translation At C9orf72-Associated Repeat Expansions Is Selectively Enhanced By The Integrated Stress Response, Katelyn M. Green, M. Rebecca Glineburg, Michael G. Kearse, Brittany N. Flores, Alexander E. Linsalata, Stephen J. Fedak, Aaron C. Goldstrohm, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G4C2 repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome. We find that C9RAN translation initiates through a cap- and eIF4A-dependent mechanism that utilizes a CUG start codon. C9RAN and CGG RAN are both selectively enhanced by integrated stress response (ISR) activation. ISR-enhanced RAN translation requires an …


Changes In The Utilization Of Osteoporosis Drugs After The 2010 Fda Bisphosphonate Drug Safety Communication, Bander Balkhi, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio Dec 2017

Changes In The Utilization Of Osteoporosis Drugs After The 2010 Fda Bisphosphonate Drug Safety Communication, Bander Balkhi, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Introduction

In October 2010, the US Food and Drug Administration (FDA) issued a safety communication regarding the risks of atypical fractures of the femur, with bisphosphonates drugs. This study evaluated the impact of the bisphosphonates FDA safety communication on the utilization of osteoporosis medications in Medicaid programs.

Methods

Osteoporosis drugs utilization data from the July 2006 to June 2014 were extracted from the national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services (CMS). We performed an interrupted time series analyses to evaluate trends in utilization of osteoporosis drugs before and …


Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang Dec 2017

Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …


Prenatal Opioid Exposure And Intermittent Hypoxemia In Preterm Infants: A Retrospective Assessment, Elie G. Abu Jawdeh, Philip M. Westgate, Amrita Pant, Audra L. Stacy, Divya Mamilla, Aayush Gabrani, Abhijit R. Patwardhan, Henrietta S. Bada, Peter J. Giannone Dec 2017

Prenatal Opioid Exposure And Intermittent Hypoxemia In Preterm Infants: A Retrospective Assessment, Elie G. Abu Jawdeh, Philip M. Westgate, Amrita Pant, Audra L. Stacy, Divya Mamilla, Aayush Gabrani, Abhijit R. Patwardhan, Henrietta S. Bada, Peter J. Giannone

Pediatrics Faculty Publications

Introduction: Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure …


Simultaneous Uplc–Ms/Ms Analysis Of Two Stable Isotope Labeled Versions Of Sucrose In Mouse Plasma And Brain Samples As Markers Of Blood-Brain Barrier Permeability And Brain Vascular Space, Ekram Ahmed Chowdhury, Saad Alqahtani, Raktima Bhattacharya, Reza Mehvar, Ulrich Bickel Dec 2017

Simultaneous Uplc–Ms/Ms Analysis Of Two Stable Isotope Labeled Versions Of Sucrose In Mouse Plasma And Brain Samples As Markers Of Blood-Brain Barrier Permeability And Brain Vascular Space, Ekram Ahmed Chowdhury, Saad Alqahtani, Raktima Bhattacharya, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with low permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labelled [13C12]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling. The …


Lyme Disease: An Influential Outdoor Hazard, Kevin Kang Dec 2017

Lyme Disease: An Influential Outdoor Hazard, Kevin Kang

Dartmouth Undergraduate Journal of Science

Lyme disease is an important, common illness in New England. A relatively new illness, it was discovered about forty years ago in the town of Lyme, Connecticut. Now, it has become the most common vector-transmitted illness in the United States, with over 30,000 cases annually. Lyme disease arises when a bacterium is transmitted to a human via deer tick bite, so those of us involved in outdoor sports are most likely to contract the disease. Inhabitants of New England and the northeastern U.S. are most vulnerable to the disease, as 95% of Lyme Disease cases occur in only 14 out …


Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh Dec 2017

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations & Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …


Investigating The Regulation Of Indole-3-Acetic Acid Production By The Plant Associated Microbe Pantoea Sp. Yr343, Kasey Noel Estenson Dec 2017

Investigating The Regulation Of Indole-3-Acetic Acid Production By The Plant Associated Microbe Pantoea Sp. Yr343, Kasey Noel Estenson

Doctoral Dissertations

The auxin indole-3-acetic acid (IAA) plays a central role in plant growth and development and many plant-associated microbes produce IAA. Several IAA biosynthetic pathways have been identified in microbes which use the precursor tryptophan. Pantoea sp. YR343, which was isolated from the Populus deltoides rhizosphere, is a robust plant root colonizer that produces IAA. Using genomic and metabolomics analyses, we predicted that the indole-3-pyruvate (IPA) pathway is the major pathway in Pantoea sp. YR343 for IAA production. To better understand IAA biosynthesis and the effects of IAA exposure on cell physiology, we performed proteomics on Pantoea sp. YR343 grown in …


A Deafness Mechanism Of Digenic Cx26 (Gjb2) And Cx30 (Gjb6) Mutations: Reduction Of Endocochlear Potential By Impairment Of Heterogeneous Gap Junctional Function In The Cochlear Lateral Wall, Ling Mei, Jin Chen, Liang Zong, Yan Zhu, Chun Liang, Raleigh O. Jones, Hong-Bo Zhao Dec 2017

A Deafness Mechanism Of Digenic Cx26 (Gjb2) And Cx30 (Gjb6) Mutations: Reduction Of Endocochlear Potential By Impairment Of Heterogeneous Gap Junctional Function In The Cochlear Lateral Wall, Ling Mei, Jin Chen, Liang Zong, Yan Zhu, Chun Liang, Raleigh O. Jones, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26+/−/Cx30+/−) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26+/−/Cx30+/− heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26−/−) mice, the cochlea in Cx26 …


Increasing Depression Screenings In Adults With Advanced Non-Surgical Heart Failure Using 2013 Accf/Aha Recommendations And Healthy People 2020 Target Goals, Valerie Valencia Dec 2017

Increasing Depression Screenings In Adults With Advanced Non-Surgical Heart Failure Using 2013 Accf/Aha Recommendations And Healthy People 2020 Target Goals, Valerie Valencia

Doctor of Nursing Practice

The purpose of this evidence-based practice project was to increase depression screenings in adults with non-surgical advanced heart failure using reliable and valid tools, 2013 American College of Cardiology Foundation/American Heart Association recommendations, and Healthy People 2020 Target Goals as a method to identify and facilitate appropriate mental health referral, patient education, and follow-up for depressive symptoms. Interventions took place June 5, 2017, through August 10, 2017. This intervention project involving 246 adults with advanced heart failure demonstrated that an evidence-based intervention for depression screenings increased the number of patients screened from 5% to 44%. At project completion, 65% of …


Improving Vaccination Rates In Adults With Type Ii Diabetes In A Family Practice Setting: An Evidence-Based Quality Improvement Project, Ronda Gottlieb Dec 2017

Improving Vaccination Rates In Adults With Type Ii Diabetes In A Family Practice Setting: An Evidence-Based Quality Improvement Project, Ronda Gottlieb

Doctor of Nursing Practice

The purpose of this evidenced-based quality improvement project is to implement processes to facilitate providers’ adherence to the American Diabetes Association (2017), American Association of Clinical Endocrinologist (2015), and American College of Endocrinology (2015) immunization guidelines for adults with type II diabetes. Presently, diabetes is the 7th leading cause of death in the United States contributing to serious complications throughout the body as a result of poor glucose control. Adults with diabetes are at increased susceptibility to infectious disease because of hyperglycemia, poor glucose control, and decreased immunity. A protocol was created using The Four Pillars Transformation Program ™ to …


Prevalence Of Chronic Obstructive Pulmonary Disease (Copd) In China In 1990 And 2010., Kit Yee Chan, Xue Li, Wanjing Chen, Peige Song, Nuen Wing Katy Wong, Adrienne N Poon, Weiyan Jian, Ireneous N Soyiri, Simon Cousens, Davies Adeloye, Aziz Sheikh, Harry Campbell, Igor Rudan, Global Health Epidemiology Research Group (Gherg). Dec 2017

Prevalence Of Chronic Obstructive Pulmonary Disease (Copd) In China In 1990 And 2010., Kit Yee Chan, Xue Li, Wanjing Chen, Peige Song, Nuen Wing Katy Wong, Adrienne N Poon, Weiyan Jian, Ireneous N Soyiri, Simon Cousens, Davies Adeloye, Aziz Sheikh, Harry Campbell, Igor Rudan, Global Health Epidemiology Research Group (Gherg).

Medicine Faculty Publications

Background: Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020. In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden. An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.

Methods: We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of …


X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors Dec 2017

X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors

Neurology Faculty Publications

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, …


24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors Dec 2017

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 …


Clinical And Serological Features Of Systemic Sclerosis In A Multicenter African American Cohort: Analysis Of The Genome Research In African American Scleroderma Patients Clinical Database, Nadia Morgan, Ami Shah, Maureen Mayes, Robyn Domsic, Thomas Medsger, Victoria K. Shanmugam, +Several Additional Authors Dec 2017

Clinical And Serological Features Of Systemic Sclerosis In A Multicenter African American Cohort: Analysis Of The Genome Research In African American Scleroderma Patients Clinical Database, Nadia Morgan, Ami Shah, Maureen Mayes, Robyn Domsic, Thomas Medsger, Victoria K. Shanmugam, +Several Additional Authors

Medicine Faculty Publications

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).

African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987–2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.

The study population included …


Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott Dec 2017

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …


Behavioral Ecology And Associated Virology Of Mosquito-Host Interactions In Southern California, Oliver Eshun Dec 2017

Behavioral Ecology And Associated Virology Of Mosquito-Host Interactions In Southern California, Oliver Eshun

Loma Linda University Electronic Theses, Dissertations & Projects

Elucidating characteristics of mosquito-host interactions are critical for understanding the ecology and epidemiology of mosquito-borne diseases. In this dissertation, I conducted three studies to explore potential mosquito-host interactions and associated virus infection rates. I first demonstrated that mosquito captures at CO2-baited traps decreased most markedly with height above ground, and also decreased with distance from water at a riparian area but not at an open water source lacking a vegetated border. Birds might therefore prefer elevated nests or roosts to avoid mosquitoes. The second study examined the anti-mosquito behaviors of budgerigars (Melopsittacus undulatus) in a laboratory study. The birds defended …


Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff Dec 2017

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …


Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli Dec 2017

Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli

Graduate Theses and Dissertations

Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic method …


Successful Reversal Of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet., Tarak Srivastava, Shahryar Jafri, William E. Truog, Judith Sebestyen Vansickle, Winston M. Manimtim, Uri S. Alon Dec 2017

Successful Reversal Of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet., Tarak Srivastava, Shahryar Jafri, William E. Truog, Judith Sebestyen Vansickle, Winston M. Manimtim, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL. After introduction of the calcimimetic Cinacalcet, we observed a sustained normalization of parathyroid hormone concentration at 27 to 63 pg/mL …