Digital Commons Network^™

A Case Of Thrombosis And Thromboembolic Events, Daniel Lin

The Medicine Forum

A 65 year old black woman with hypertension (HTN), gastroesophageal reflux disease (GERD), and anxiety had complained to her primary care physician of vague abdominal pain. Initial empiric treatment as an outpatient for worsening GERD was unsuccessful. The patient had insidious development of generalized fatigue, early satiety, nausea, vomiting, and weight loss. An ultrasound of the abdomen revealed multiple liver lesions, with the largest lesion being 2.5 cm x 2.5 cm. She subsequently underwent a CT scan of the abdomen and pelvis, which confirmed multiple hyperdense liver lesions. The remainder of the scan was unremarkable. Esophagogastroduodenoscopy (EGD) as well as …

Withanolide Compounds As Inhibitors Of Fibrosis And Identification Of Molecular Targets For Anti-Fibrotic Drug Development, Royce Mohan, Paola Bargagna-Mohan

Ophthalmology and Visual Science Faculty Patents

Provided are methods for screening for drugs effective for treating fibrotic conditions. One screening method comprises exposing a cell to a test compound, monitoring the effect of the test compound on the amount or form of a cell molecule, comparing the amount or form of the cell molecule with the result obtained by treatment of the cell with an anti-fibrotic -effective amount of a withanolide compound, and selecting a drug effective for treating a fibrotic disease based on the ability of the test compound to provide the effect obtained by the withanolide compound on the cell molecule. Also provided is …

Com Outlook Fall 2012, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Achieving Consensus On Measure-Driven Child Health Quality: Maine’S Improving Health Outcomes For Children Initiative, Martha Elbaum Williamson Mpa, Nargiza Fuzailova Md, Mph, Kimberley S. Fox Mpa

Population Health & Health Policy

This brief describes Maine’s process for selecting child health quality measures, including identified strengths and limitations of the CHIPRA core measures that led to the inclusion of additional state-specific measures and the factors considered for selection. Subsequent articles will describe how measures have been implemented and used to improve child health quality and how they have been integrated into systems of care (e.g. health information technology systems, policy changes).

Experience Of Caregivers With The Survivors Of Hepatitis C, Noureen Shehzad Jiwani, Raisa B. Gul, Rubina Sultan

School of Nursing & Midwifery

Objectives: To assess and describe the experiences of those caring for hepatitis C patients in Karachi, Pakistan.

Methods: Using a qualitative approach, the study adopted a descriptive exploratory design for which 8 caregirers were selected through snowball sampling technique from different parts of Karachi. Data was collected between May and July 2010 through semi-structured interviews from the caregivers. The interviews were recorded on tape and were transcribed verbatim. The data was manually analysed for extracting themes and categories.

Results: The analyses of data led to one theme - \'deadly, dangerous, and devastating. Two associated categories could also be noted: \'perceptions …

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …

Rethinking Hiv-Exposure Crimes, Margo Kaplan

Indiana Law Journal

This Article challenges the current legislative and scholarly approaches to HIV-exposure crimes and proposes an alternative framework to address their flaws. Twenty-four states criminalize consensual sexual activities of people with HIV. Current statutes and the scholarship that supports them focus on HIV-positive status, sexual activity, and knowledge of HIV-positive status as proxies for risk, mental state, and consent to risk. As a result, they are dramatically over- and underinclusive and stigmatize individuals living with HIV. Criminalization should be limited to circumstances in which a defendant exposed her partner to a substantial degree of unassumed risk and did so with a …

Antenatal Care And The Occurrence Of Low Birth Weight Delivery Among Women In Remote Mountainous Region Of Chitral, Pakistan, Z. Ahmed, S. Khoja, Suha S. Tirmizi

Obstetrics and Gynaecology, East Africa

Objective: Low birth weight (LBW) is closely associated with perinatal morbidity and bears an increased risk for subsequent infant morbidity. The study aimed to assess low birth weight delivery factors among women in Chitral, Pakistan.

Methodology: Mixed Methodology was adopted. Structured data collection tool was used to collect information from medical records of 1316 mothers, followed by interviews and focus group discussions to understand the causes and their remedies. The main outcome measure was infants born with low birth weight LBW (<2.5kg).

Result: There was a significant association between the occurrence of low birth weight and maternal education, paternal education, …

The Effect Of Genetic Background And Dose On Non-Targeted Effects Of Radiation, Sarah Irons, Virginia Sierra, Deborah Bowler, Kim Chapman, Stefania Militi, Fiona Lyng, Munira Kadhim

Articles

Purpose: This work investigates the hypothesis that genetic background plays a significant role in the signalling mechanisms underlying induction and perpetuation of genomic instability following radiation exposure.

Materials and methods: Bone marrow from two strains of mice (CBA and C57) were exposed to a range of X-ray doses (0, 0.01, 0.1, 1 and 3 Gy). Different cellular signalling endpoints: Apoptosis, cytokine levels and calcium flux, were evaluated at 2 h, 24 h and 7 d post-irradiation to assess immediate and delayed effects.

Results: In CBA (radiosensitive) elevated apoptosis levels were observed at 24 h post X-irradiation, and …

Oncolog, Volume 57, Number 10, October 2012, Jill Delsigne, Sunni Hosemann

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Treatments May Alleviate and Reverse Central Nervous System Radiation Necrosis: Although radiation therapy is effective against many tumors of the brain and spine, it also damages normal tissue
• INBRIEF: Bevacizumab With High-Dose Chemotherapy Shows Promise for Cisplatin-Refractory Germ Cell Tumors
• Compass: Early-Stage Testicular Cancer-Postsurgical treatment varies according to tumor stage and histology
• HOUSE CALL: Online Cancer Support Networks-Patients and caregivers find support online

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …

Good Knowledge About Hypertension Is Linked To Better Control Of Hypertension; A Multicentre Cross Sectional Study In Karachi, Pakistan, Aysha Almas, Saniya Siraj Godil, Saima Lalani, Zahra Aziz Samani, Aamir Hameed

Section of Internal Medicine

Back Ground: According to the National Health survey only 3% of the population has controlled hypertension. This study was designed to elucidate the knowledge about hypertension in hypertensive patients at three tertiary care centers in Karachi. Secondly we sought to compare the knowledge of those with uncontrolled hypertension and controlled hypertension.

Methods: It was a cross-sectional study conducted at The Aga Khan University hospital (AKUH), Ziauddin Hospital (ZH) and Civil hospital, Karachi (CHK. All diagnosed Hypertensive patients (both inpatients and outpatients) coming to a tertiary care hospital in Pakistan aged > 18 years were included. Patients were categorized into 2 groups: …

Orientation-Invariant Ecg-Based Virtual Pathology Stethoscope Tracking For Standardized Patient Heart Auscultation, Nahom B. Kidane

Computational Modeling & Simulation Engineering Theses & Dissertations

Cardiac auscultation (CA), the act of listening to the heart sounds, is a critical physician's skill that provides substantial information for diagnosing many cardiovascular disorders; therefore, competent training can be a key for accurate and reliable diagnosis. The teaching of CA has been an area of recognized importance since the inception of the stethoscope. However, recent changes in health-care, such as limited student access to patients and higher reliance on competing technologies have made it challenging to teach bedside CA techniques.

Over the past few decades, standardized patients (SPs), individuals trained to portray real patients, have been widely used for …

Awareness Of Type Ii Diabetes In The Developing World: Case Study In Binh Du’O’Ng, Vietnam, Anna Hong Le

Independent Study Project (ISP) Collection

Vietnam’s rapid economic development after 1986 forever changed the lifestyle of the Vietnamese. Economic development has highly impacted behavior, “changing from a traditional lifestyle to an industrial lifestyle [increasing] noncommunicable diseases (NCDs) : diabetes, overweight, high blood pressure, and high cholesterol disorders” (Danh, Personal Interview). With the increase of NCDs within the country, it is important to focus on awareness education that motivates the population especially those living in the urban sector to practice healthy behaviors. This study project focuses on the evaluating the reach and effectiveness of current diabetes awareness educational materials. One week was spent in Ha Noi, …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms In Angiotensin Ii-Infused Mice, Xiaojie Xie, Hong Lu, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways., Douglas N Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S Shaw, Jill Roberts, Gregory J Bix

Department of Dermatology and Cutaneous Biology Faculty Papers

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways, Douglas N. Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S. Shaw, Jill Roberts, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Human Cytomegalovirus Induces Tlr4 Signaling Components In Monocytes Altering Tirap, Tram And Downstream Interferon-Beta And Tnf-Alpha Expression., Kok-Hooi Yew, Cory Carpenter, R Scott Duncan, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Using TLR pathways, primary human cytomegalovirus (HCMV) induces innate responses including the production of inflammatory cytokines. Mounting evidence suggests that LPS recognition by TLR4/MD2/CD14 results in differential utilization of TIRAP-TRAF6 and TRAM-TRIF signaling, thereby leading to transcriptional activation of various cytokine genes. However, relative roles of the TLR4/MD2/CD14 complex and its adaptor proteins TIRAP and TRAM involved in regulating monocyte responses to HCMV are incomplete. Here, we provided evidence supporting the notion that the TLR4/MD2/CD14 complex contributes notably to HCMV-induced signaling and subsequent cytokine production in monocytes. In particular, induction of both IL-6 and IL-8 is associated with elevated TIRAP …

Life History Theory And Social Psychology., Donald F Sacco, Karol Osipowicz

Department of Neurology Faculty Papers

No abstract provided.

The Training Of A 'Stone Doctor', Jamsheer J. Talati

Section of Urology

Objective: To propose alternative models of training for doctors treating patients with stones, and to identify their relative value, as such doctors are trained through urology programmes which sometimes cannot be expanded to meet the need, are short of teachers, too comprehensive and lengthy. This review explores new pathways for training to provide competence in the care of patients with stones.
Methods: Previous reports were identified and existing training models collectively categorised as Model 1. Three alternative models were constructed and compared in the context of advantages, acceptability, feasibility, educational impact and applicability in different geosocio-political contexts.
Results: In Model …

25(Oh)D3 And Cardiovascular Risk Factors In Female Nonhuman Primates., Matthew J Jorgensen, Lawrence L Rudel, Matthew Nudy, Jay R Kaplan, Thomas B Clarkson, Nicholas M Pajewski, Peter F Schnatz

Division of Internal Medicine Faculty Papers & Presentations

OBJECTIVE: To determine if interindividual differences in plasma concentrations of 25-hydroxyvitamin D(3) (25(OH)D(3)) have pathophysiologic significance, we evaluated a cohort of female monkeys, seeking to identify associations with clinically relevant cardiovascular risk factors, including age, abdominal obesity (waist circumference), and high-density lipoprotein cholesterol (HDL-C).

METHODS: One hundred fifty-five female vervet monkeys (Chlorocebus aethiops sabaeus) aged 3-25 years consumed a typical western diet for 7-8 weeks that provided a woman's equivalent of approximately 1000 IU/day of vitamin D(3). Measurements of vitamin D(3) and HDL-C concentrations, as well as waist circumference, were obtained.

RESULTS: Among young monkeys (aged 3-5 years), compared to …

Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin

Physiology Faculty Publications

Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.

Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.

Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and …

Biosynthetic Pathways And The Role Of The Mas Receptor In The Effects Of Angiotensin-(1-7) In Smooth Muscles., Marcio Augusto Fressatto De Godoy, Larissa Pernomian, Ana Maria De Oliveira, Satish Rattan

Department of Medicine Faculty Papers

Ang-(1-7) is produced via degradation of Ang II by the human angiotensin converting enzyme, also known as ACE2. In the cardiovascular system, Ang-(1-7) has been shown to produce effects that are opposite to those of Ang II. These include smooth muscle relaxation and cardioprotection. While the roles of Ang-(1-7) in other systems are currently topic of intense research, functional data suggest a relaxation action in gastrointestinal smooth muscles in a way that corroborates the results obtained from vascular tissues. However, more studies are necessary to determine a relevant role for Ang-(1-7) in the gastrointestinal system. The Ang-(1-7) actions are mediated …

Herpes Simplex Virus 34.5 Interferes With Autophagosome Maturation And Antigen Presentation In Dendritic Cells, Philipe A. M. Gobeil, David A. Leib

Dartmouth Scholarship

The cellular autophagy response induced by herpes simplex virus 1 (HSV-1) is countered by the viral γ34.5 protein. γ34.5 modulates autophagy by binding to the host autophagy protein Beclin-1 and through this binding inhibits the formation of autophagosomes in fibroblasts and neurons. In contrast, in this study dendritic cells (DCs) infected with HSV-1 showed an accumulation of autophagosomes and of the long-lived protein p62. No such accumulations were observed in DCs infected with a γ34.5-null virus or a virus lacking the Beclin-binding domain (BBD) of γ34.5. To explore this further, we established stably transduced DC lines to show that γ34.5 …

Effectiveness Of A Peer-Led Hiv Prevention Intervention In Secondary Schools In Rwanda: Results From A Non-Randomized Controlled Trial, Kristien Michielsen, Roxanne Beauclair, Wim Delva, Kristien Roelens, Ronan Van Rossem, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: While the HIV epidemic is levelling off in sub-Saharan Africa, it remains at an unacceptably high level. Young people aged 15-24 years remain particularly vulnerable, resulting in a regional HIV prevalence of 1.4% in young men and 3.3% in young women. This study assesses the effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda on young people’s sexual behavior, HIV knowledge and attitudes.

Methods: In a non-randomized longitudinal controlled trial, fourteen schools were selected in two neighboring districts in Rwanda Bugesera (intervention) and Rwamagana (control). Students (n= 1950) in eight intervention and six control schools participated …

Genetics For The Ophthalmologist., Karthikeyan A Sadagopan, Jenina Capasso, Alex V Levin

Wills Eye Hospital Papers

The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails), nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in …

Use Of Quantitative Membrane Proteomics Identifies A Novel Role Of Mitochondria In Healing Injured Muscles., Nimisha Sharma, Sushma Medikayala, Sree Rayavarapu, Kristy J. Brown, Yetrib Hathout, Jyoti K. Jaiswal, Aurelia Defour

Pediatrics Faculty Publications

Skeletal muscles are proficient at healing from a variety of injuries. Healing occurs in two phases, early and late phase. Early phase involves healing the injured sarcolemma and restricting the spread of damage to the injured myofiber. Late phase of healing occurs a few days postinjury and involves interaction of injured myofibers with regenerative and inflammatory cells. Of the two phases, cellular and molecular processes involved in the early phase of healing are poorly understood. We have implemented an improved sarcolemmal proteomics approach together with in vivo labeling of proteins with modified amino acids in mice to study acute changes …

Automatic And Robust Calibration Of Optical Detector Arrays For Biomedical Diffuse Optical Spectroscopy, Michael A. Mastanduno, Shudong Jiang, Roberta Diflorio-Alexander, Brian W. Pogue, Keith Paulsen

Dartmouth Scholarship

The design and testing of a new, fully automated, calibration approach is described. The process was used to calibrate an image-guided diffuse optical spectroscopy system with 16 photomultiplier tubes (PMTs), but can be extended to any large array of optical detectors and associated imaging geometry. The design goals were accomplished by developing a routine for robust automated calibration of the multi-detector array within 45 minutes. Our process was able to characterize individual detectors to a median norm of the residuals of 0.03 V for amplitude and 4.4 degrees in phase and achieved less than 5% variation between all the detectors …

Breast Milk From Tanzanian Women Has Divergent Effects On Cell-Free And Cell-Associated Hiv-1 Infection In Vitro, Magdalena A. Lyimo, Matilda Ngarina Mosi, Molly L. Housman, Muhammad Zain-Ul-Abideen, Frederick V. Lee, Alexandra L. Howell, Ruth I. Connor

Dartmouth Scholarship

Transmission of HIV-1 during breastfeeding is a significant source of new pediatric infections in sub-Saharan Africa. Breast milk from HIV-positive mothers contains both cell-free and cell-associated virus; however, the impact of breast milk on HIV-1 infectivity remains poorly understood. In the present study, breast milk was collected from HIV-positive and HIV-negative Tanzanian women attending antenatal clinics in Dar es Salaam. Milk was analyzed for activity in vitro against both cell-free and cell-associated HIV-1. Potent inhibition of cell-free R5 and X4 HIV-1 occurred in the presence of milk from all donors regardless of HIV-1 serostatus. Inhibition of cell-free HIV-1 infection positively …