Digital Commons Network^™

Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee

Journal Articles: Pulmonary & Critical Care Med

Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The …

Relationships Between Positive Psychological Constructs And Health Outcomes In Patients With Cardiovascular Disease: A Systematic Review, Christina M. Dubois, Oriana Vesga Lopez, Eleanor E. Beale, Brian C. Healy, Julia K. Boehm, Jeff C. Huffman

Psychology Faculty Articles and Research

Depression and anxiety are well-known to be associated with adverse health outcomes in cardiac patients. However, there has been less work synthesizing the effects of positive psychological constructs (e.g., optimism) on health-related outcomes in cardiac patients. We completed a systematic review of prospective observational studies using established guidelines. A search of PubMed and PsycINFO databases from inception to January 2014 was used to identify articles. To be eligible, studies were required to assess effects of a positive psychological construct on subsequent health-related outcomes (including mortality, rehospitalizations, self-reported health status) in patients with established heart disease. Exploratory random effects' meta-analyses were …

New Film Unmasks The Raw Reality Of Huntington’S Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Highly Stable Prefusion Rsv F Vaccine Derived From Structural Analysis Of The Fusion Mechanism, Anders Krarup, Daphné Truan, Polina Furmanova-Hollenstein, Lies Bogaert, Pascale Bouchier, Ilona Bisschop, Myra Widjojoatmodjo, Roland Zahn, Hanneke Schuitemaker, Jason Mclellan, Johannes Langedijk

Dartmouth Scholarship

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion …

Nut Consumption And Cardiovascular Risk In Older Chinese: The Guangzhou Biobank Cohort Study, Yangbo Sun, Chao Qiang Jiang, Kar Keung Cheng, Wei Sen Zhang, Gabriel M. Leung, Tai Hing Lam, Mary Schooling

Publications and Research

Objectives
In Western contexts nut consumption is associated with better health. We examined the associations of nut consumption with cardiovascular disease risk in the non-Western setting of Southern China.

Methods
In the Guangzhou Biobank Cohort Study we used multivariable linear regression to examine the associations of baseline nut (mainly peanuts) consumption (none (n = 6688),/ week (n = 2596) and _3 portions/week (n = 2444)) with follow-up assessment of Framingham cardiovascular disease score (excluding smoking) and its components in older Chinese (_50 years) (follow-up 57.8%).

Results
Nut consumption was not associated with Framingham score (_3 portions/week compared to none: 0.02 …

Speckle-Tracking Echocardiographic Measures Of Right Ventricular Function Correlate With Improvement In Exercise Function After Percutaneous Pulmonary Valve Implantation., Shahryar M. Chowdhury, Ziyad M. Hijazi, John T. Fahey, John F. Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to improve after transcatheter pulmonary valve implantation (TPVI). Measures of exercise function, such as ventilatory efficiency (the minute ventilation [VE]/carbon dioxide production [VCO2] slope), have been shown to be prognostic of mortality in patients who may require TPVI. The aim of this study was to evaluate the correlation between STE measures of RV function and changes in VE/VCO2 after TPVI.

METHODS: Speckle-tracking echocardiography and cardiopulmonary exercise testing were performed at baseline and 6 months after TPVI in 24 patients from four centers. Conventional echocardiographic measures of RV function were …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Risk Of Death From Cardiovascular Disease Associated With Low-Level Arsenic Exposure Among Long-Term Smokers In A Us Population-Based Study, Shohreh F. Farzan, Yu Chen, Judy R. Rees, M. Scot Zens, Margaret Karagas

Dartmouth Scholarship

High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic’s effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, …

Commentary On "Systemic Candidiasis And Cytomegalovirus Infection In The Setting Of Artificial Cardiac Device Deployment", Moises A. Huaman

The VAD Journal

No abstract provided.

Chronic Ldh Elevation After Left Ventricular Assist Device Implantation, Hesham R. Omar, Navin Rajagopalan, Maya Guglin

The VAD Journal

A 61-year-old woman who underwent HeartMate II left ventricular assist device placement for non-ischemic cardiomyopathy developed elevated lactate dehydrogenase within two weeks after implantation. After eight months of observation and several hospital admissions during which there was no evidence of pump thrombosis, she presented with clinically manifest hemolysis. During pump exchange there was notable pannus formation on the inflow cannula of the left ventricular assist device. The pannus around the inflow likely existed for several months, limiting the flow and creating a low-grade hemolysis and this low flow state stimulated thrombus formation triggering gross hemolysis. Thoratec analysis of the pump …

Reinforcing The Global Fight Against Huntington’S Disease: A Visit To Brazil And A Reminder Of Our Common Struggles, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Ccr5 And The Blood Brain Barrier During Hiv-1 Infection And Cell-Cell Communications, Shawna M. Woollard

Theses & Dissertations

Human Immunodeficiency Virus (HIV-1) infection often results in blood-brain barrier (BBB) dysfunction and central nervous system (CNS) impairment. Since most viral strains that cross the BBB and enter the CNS are macrophage-tropic and use the C-C chemokine receptor type-5 (CCR5) to enter and infect target cells, we hypothesized that CCR5 plays a major role in monocytes-endothelial interactions and HIV-induced BBB dysfunction. Because the cytoskeleton is responsible for cellular morphology and motility, we further hypothesized that HIV-induced monocyte-endothelial interactions and transendothelial migration involve cytoskeletal changes and that CCR5 blockers would also affect these changes. To this end we used two small …

Clinical Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Surgery In High Surgical Risk Patients With Left Main Or Three-Vessel Coronary Artery Disease, Tonga Nfor, Kambiz Shetabi, Wael Hassan, Quinta Nfor, Jayant Khitha, Anjan Gupta, Tanvir Bajwa, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose

Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass graft surgery (CABG) in patients with unprotected left main or three-vessel coronary artery disease (LM-3VD) have excluded patients at high surgical risk. We compared clinical outcomes after PCI with drug-eluting stents to CABG in high surgical risk patients with LM-3VD.

Methods

Patients with symptomatic LM-3VD who had Society of Thoracic Surgeons (STS)-predicted operative mortality >5% and were undergoing either PCI with drug-eluting stents or CABG at a tertiary care center from January 2009 to December 2010 were enrolled in this nonrandomized prospective study.

Results

Mean STS score was …

New Paradigms In The Treatment Of Acute Complicated And Uncomplicated Type B Aortic Dissection, Eric S. Weiss

Journal of Patient-Centered Research and Reviews

The treatment of acute type B aortic dissection is a rapidly evolving field, due in a large part to the advent of thoracic endovascular aortic repair (TEVAR). This review will summarize the current literature on the management of both complicated and uncomplicated type B dissections, with special attention paid to emerging evidence supporting earlier aggressive treatment.

Vascular Medicine: A ‘Primary’ Specialty, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

N/A

Overview Of The Role Of Duplex Ultrasound For Treatment And Surveillance Of Peripheral Arterial Disease, John H. Fish Iii, Peter Klein-Weigel, Gustav Fraedrich

Journal of Patient-Centered Research and Reviews

Imaging strategies for preinterventional planning in symptomatic peripheral artery disease have employed various modalities ranging from duplex ultrasound to noninvasive angiography with computed tomography (CT) or magnetic resonance (MRA). These methods have classically been compared to the gold standard of digital subtraction angiography and are reviewed here in detail through the work of relevant published studies and meta-analyses between 1996 and 2014. In particular, we focus on the diagnostic performance, reproducibility and cost-effectiveness of these aforementioned modalities with respect to mapping the lower extremity arterial tree for planning vascular intervention and surveillance. The data presented suggests comparable sensitivity and specificity …

Subclavian Vein Stenosis/Occlusion Following Transvenous Cardiac Pacemaker And Defibrillator Implantation: Incidence, Pathophysiology And Current Management, Brian O'Leary, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Subclavian vein stenosis is a common, but usually asymptomatic, complication following cardiac device placement. In addition to reviewing the literature on incidence, pathogenesis and management options for this important clinical problem, we describe two cases of symptomatic subclavian vein occlusion following pacemaker/defibrillator placement and successful treatment with venoplasty and stenting.

Type Ii Endoleak Following Endovascular Repair Of Infrarenal Abdominal Aortic Aneurysm: Innovative Transgraft Approach To Contemporary Management, M. Fuad Jan, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

Elective endovascular aneurysm repair (EVAR) is the first-line therapeutic option for patients with infrarenal abdominal aortic aneurysm. However, endoleaks –– persistent blood flow outside the lumen of the stent graft (or endograft) but within the aneurysm sac or adjacent vascular segment being treated by the graft –– continue to be a persistent problem in the post-EVAR setting. The type II endoleak is the most common of these and can be a demanding challenge to address by standard endovascular techniques. Currently, two prominent endovascular techniques exist for the management of type II endoleaks: direct translumbar embolization and transarterial embolization. Both of …

Use Of Coronary Techniques In Celiac And Hepatic Artery Stenting In Post-Hepatic Transplant Patients, Harpreet Parmar, Ryan Beard, Mark W. Mewissen, Armaan Shaikh, Tanvir Bajwa

Journal of Patient-Centered Research and Reviews

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed, …

Novel Oral Anticoagulants For Stroke Prophylaxis And Venous Thromboembolism Prevention And Treatment, Laith G. Alsayegh

Journal of Patient-Centered Research and Reviews

Novel oral anticoagulants (NOACs) are becoming popular management options for stroke prophylaxis in nonvalvular atrial fibrillation as well as deep vein thrombosis and pulmonary embolism treatment and prophylaxis. NOACs have similar efficacy to warfarin along with noninferior safety profiles. Patient comorbidities, size, renal and hepatic function, and concomitant drug regimen play a role in which NOAC a physician may choose.

Fruit And Vegetable Consumption And Cardiovascular Risk Factors In Older Chinese: The Guangzhou Biobank Cohort Study, Yangbo Sun, Chao Qiang Jiang, Kar Keung Cheng, Wei Sen Zhang, Gabriel M. Leung, Tai Hing Lam, Mary Schooling

Publications and Research

Objective
To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non-Western setting of Southern China, considering health status.

Method
Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003– 2006), and whether these differed by health status.

Results
The association of fruit consumption with the Framingham score varied by health status (P-value

Conclusion
This large study from a non-western setting found that …

Investigation Of Stilbenoids As Potential Therapeutic Agents For Rotavirus Gastroenteritis, Judith M. Ball, Fabricio Medina-Bolivar, Katelyn D. Defrates, Emily Hambleton, Megan E. Hurlburt, Lingling Fang, Tianhong Yang, Luis Nopo-Olazabal, Richard L. Atwill, Pooj Ghai, Rebecca D. Parr

Faculty Publications

Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced …

Muc16-Mediated Activation Of Mtor And C-Myc Reprograms Pancreatic Cancer Metabolism., Surendra K. Shukla, Venugopal Gunda, Jaime Abrego, Dhanya Haridas, Anusha Mishra, Joshua J. Souchek, Nina V. Chaika, Fang Yu, Aaron R. Sasson, A Lazenby, Surinder K. Batra, Pankaj K. Singh

Journal Articles: Eppley Institute

MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global …

Changes In Vessel Properties During Early Progression Of Murine Abdominal Aortic Aneurysms From In Vivo Ultrasound, Luis R. Avila Murati, Evan H. Phillips, Craig J. Goergen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Abdominal aortic aneurysms (AAA) are a common and frequently fatal disease characterized by the weakening and dilation of the aorta. The larger the aneurysm, the higher the chances are of rupturing and life-threatening hemorrhage. The aim of this study is to apply the angiotensin II (AngII) model of AAAs in male apolipoprotein-E-deficient mice (apoE^-/- C57Bl/6J), in order to analyze, quantify, and understand the pathologies and characteristics associated with early AAA development. To date, many studies focusing on the evaluation of AAA characteristics have been performed ex vivo. Therefore, we focused on in vivo assessment, through the use of …

Microrna-587 Antagonizes 5-Fu-Induced Apoptosis And Confers Drug Resistance By Regulating Ppp2r1b Expression In Colorectal Cancer., Yinbo Zhang, Geoffrey Talmon, Jing Wang

Journal Articles: Eppley Institute

Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-587 modulates drug resistance through downregulation of expression of PPP2R1B, a regulatory subunit of the PP2A complex, which negatively regulates AKT activation. Knockdown of PPP2R1B expression increases AKT phosphorylation, which leads to elevated XIAP expression and enhanced …

End Stage Renal Disease: Seroprevalence Of Hepatitises B And C Along With Associated Aetiology And Risk Factors In Children, Syed Raza Shah, Muhammad Shahzeb Khan, Muhamad Tanveer Alam, Adnan Salim, Mehwish Hussain, Areeba Altaf

Section of Neurosurgery

Background: End Stage Renal Disease (ESRD) normally requires dialysis or transplantation for survival. Since ESRD patients are on long term dialysis, infections such as Hepatitis B (HBV) and Hepatitis C (HCV) are commonly reported.
Methods: This was a retrospective study carried out at a government hospital during a 12-month period from January 2013 to December 2013. The data was collected using a predesigned pro forma to note the etiology, gender, age, and HBsAg and anti-HCV test result of each patient.
Results: 444 children suffering from ESRD were included in our analysis. The mean age of sample was 12.7 ± 4.1 …

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …

Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty Scholarship

We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated in Kampala in 2014. By standard in vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). By the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable in 40 of 43 cultures at 72 h. Two of 53 isolates had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia. Thus, we did not see evidence for artemisinin resistance in Uganda.

Acute Myocardial Infarction And Myocardial Ischemia-Reperfusion Injury: A Comparison, Satwat Hashmi, Suhail Al-Salam

Department of Biological & Biomedical Sciences

Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as 'reperfusion injury' (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as …

Prevalence Of A Chytrid Pathogen (Batrachochytrium Dendrobatidis) In Eastern Hellbender Salamanders In New York And Pennsylvania, Linxuan Wu

Biology Theses

Amphibian populations are currently declining globally. There are many possible causes for these declines, among which an emerging infectious disease, chytridiomycosis, has been implicated. Chytridiomycosis in the U.S.A. is mainly caused by the Batrachochytrium dendrobatidis. In this study, I used qPCR assays to detect the existence of this pathogen in the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) populations in the Allegheny and Susquehanna River drainages of New York and Pennsylvania. Chytrid is most often tested by using skin swabs, but in this study, tail clips, dorsal skin, blood and eggs were tested as well. Batrachochytrium dendrobatidis was detected …