Digital Commons Network^™

Preparation And Characterization Of Anti-Hiv Nanodrug Targeted To Microfold Cell Of Gut-Associated Lymphoid Tissue, Upal Roy, Hong Ding, Sudheesh Pilakka-Kanthikeel, Andrea D. Raymond, Venkata Atluri, Adriana Yndart, Elena M. Kaftanovskaya, Elena Batrakova, Marisela Agudelo, Madhavan Nair

Health & Biomedical Sciences Faculty Publications

The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host–pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a …

Role Of Mrp Transporters In Regulating Antimicrobial Drug Inefficacy And Oxidative Stress-Induced Pathogenesis During Hiv-1 And Tb Infections, Upal Roy, Paul Barber, Yuk-Ching Tse-Dinh, Elena V. Batrakova, Debasis Mondal, Madhavan Nair

Health & Biomedical Sciences Faculty Publications

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses …

Towards A New Global Strategy For Women’S, Children’S And Adolescents’ Health, Marleen Temmerman, Rajat Khosla, Zulfiqar Ahmed Bhutta, Flavia Bustreo

Obstetrics and Gynaecology, East Africa

The year 2015 marks a defining moment for the health of women, children, and adolescents. It is the end point of the United Nations’ millennium development goals, and their transition to the sustainable development goals, and also the 20th anniversary of the International Conference on Population and Development’s plan of action and the Beijing Declaration and platform of action.

This is a moment of reflection as well as celebration. Although great strides have been made in reducing maternal and child mortality, showing that change is possible, many countries are lagging behind in reaching millennium development goal 4 (to reduce the …

Dissecting Tumor Metabolic Heterogeneity: Telomerase And Large Cell Size Metabolically Define A Sub-Population Of Stem-Like, Mitochondrial-Rich, Cancer Cells., Rebecca Lamb, Bela Ozsvari, Gloria Bonuccelli, Duncan L Smith, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Md, Robert B Clarke, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Faculty Papers

Tumor cell metabolic heterogeneity is thought to contribute to tumor recurrence, distant metastasis and chemo-resistance in cancer patients, driving poor clinical outcome. To better understand tumor metabolic heterogeneity, here we used the MCF7 breast cancer line as a model system to metabolically fractionate a cancer cell population. First, MCF7 cells were stably transfected with an hTERT-promoter construct driving GFP expression, as a surrogate marker of telomerase transcriptional activity. To enrich for immortal stem-like cancer cells, MCF7 cells expressing the highest levels of GFP (top 5%) were then isolated by FACS analysis. Notably, hTERT-GFP(+) MCF7 cells were significantly more efficient at …

Characterizing Ebola Transmission Patterns Based On Internet News Reports., J. C. Cleaton, Cecile Viboud, Lone Simonsen, A. M. Hurtado, G. Chowell

Global Health Faculty Publications

BACKGROUND:  Detailed information on patient exposure, contact patterns, and discharge status, is rarely available in real time from traditional surveillance systems in the context of an emerging infectious disease outbreak. Here we validate the systematic collection of Internet news reports to characterize epidemiological patterns of Ebola virus disease (EVD) infections during the West African 2014-2015 outbreak.

METHODS:  Based on 58 news reports, we analyzed a total of 79 EVD clusters (286 cases) of size ranging from 1 to 33 cases between January 2014 and February 2015 in Guinea, Sierra Leone and Liberia.

RESULTS AND CONCLUSIONS:  The great majority of reported …

Relationships Between Cancer Pattern, Country Income And Geographical Region In Asia., Chirk Jenn Ng, Chin Hai Teo, Nurdiana Abdullah, Wei Phin Tan, Hui Meng Tan

Department of Surgery Faculty Papers

BACKGROUND: Cancer incidence and mortality varies across region, sex and country's economic status. While most studies focused on global trends, this study aimed to describe and analyse cancer incidence and mortality in Asia, focusing on cancer site, sex, region and income status.

METHODS: Age-standardised incidence and mortality rates of cancer were extracted from the GLOBOCAN 2012 database. Cancer mortality to incidence ratios (MIRs) were calculated to represent cancer survival. The data were analysed based on the four regions in Asia and income.

RESULTS: Cancer incidence rate is lower in Asia compared to the West but for MIR, it is the …

Oncolog, Volume 60, Number 09, September 2015, Sarah Bronson, Bryan Tutt, K. Nair

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

• Enhanced Surgical Recovery Programs Improve Perioperative Outcomes for Cancer Patients: For patients undergoing cancer surgery, potential complications and long recovery times can delay the delivery of additional life-saving therapy. To improve patients' perioperative outcomes and clear the way for timely administration of additional therapies, several surgical teams at The University of Texas MD Anderson Cancer Center gave begun using enhanced surgical recovery programs (ESRPs).
• New Treatments for Respiratory Viruses in Immunocompromised Patients: Viral respiratory infections are a major concern for immunocompromised patients, in whom such infections are difficult to treat and can lead to pneumonia and even death. Although few …

Mortality In Sepsis And Its Relationship With Gender., Nosheen Nasir, Bushra Jamil, Shahla Siddiqui, Fauzia A. Khan, Rabia Hussain

Department of Medicine

BACKGROUND AND OBJECTIVE:

Sepsis remains a leading cause of death across the world, carrying a mortality rate of 20-50%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients.

METHODS:

This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNFα) levels and …

Pregnancy And Pertussis: Why The Change In Tdap Administration?, Marietta Sperry

Books, Presentations, Posters, Etc.

Background and new guidelines vs. old guidelines. Systematic review of obstacles, recommendations, and conclusions.

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 …

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

The VAD Journal

No abstract provided.

Systemic Candidiasis And Cytomegalovirus Infection In The Setting Of Artificial Cardiac Device Deployment., Manoj Thangam, Bindu Akkanti, Maan Malahafio, Sriram Nathan, Indranee Rajapreyar, Pranav Loyalka, Biswajit Kar, Igor Gregoric

The VAD Journal

Heart failure is a serious cause of morbidity and mortality worldwide. The advent of implantable cardiac assist devices has generated a new arsenal for treating severe heart failure. However, the potential ramifications of ventricular assist device (VAD) usage are not fully understood. Immune modulation resulting from VAD implantation is an area of growing research. Although we do not fully understand the mechanisms contributing to host immune alteration, changes in cytokine concentrations, deceased lymphocyte activity, and the local effects of device materials have been shown to down regulate immune function. ^7,8 Infection is a serious complication that affects prognosis in this …

Optimizing Antibiotic Stewardship In Nursing Homes: A Narrative Review And Recommendations For Improvement, Robin Jump

Faculty Scholarship

The emerging crisis in antibiotic resistance and concern that we now sit on the precipice of a post-antibiotic era have given rise to advocacy at the highest levels for widespread adoption of programmes that promote judicious use of antibiotics. These antibiotic stewardship programmes, which seek to optimize antibiotic choice when clinically indicated and discourage antibiotic use when clinically unnecessary, are being implemented in an increasing number of acute care facilities, but their adoption has been slower in nursing homes. The antibiotic prescribing process in nursing homes is fundamentally different from that observed in hospital and clinic settings, with formidable challenges …

Proton Pump Inhibitors And Corticosteroids As Synergistic Risk Factors For Candida Esophagitis, Nihar Shah Md, Yana Cavanagh, Oleg Shulik, Pooja Patel, Vincent A. Debari, Walid Baddoura

Gastroenterology

Abstract:

Introduction: Inhaled & systemic steroids are one of the well-documented risks factors for Candida esophagitis. However, the role of gastric acid suppression remains controversial.

Methods:

We conducted a retrospective case-control study of 420 patients consisting of 84 cases of Candida esophagitis and 336 matched controls. Our cohort was gathered from subjects evaluated from 2001 to 2012. The diagnosis of Candida esophagitis was based on endoscopic and/or histological criteria.

Results:

On univariate analysis, proton pump inhibitors were associated with higher risk (OR = 2.14; 95 % CI: 1.30 to 3.54); steroid use also increased the risk (OR = 3.55; 95% …

Differential Host Immune Responses After Infection With Wild-Type Or Lab-Attenuated Rabies Viruses In Dogs., Clement W Gnanadurai, Yang Yang, Ying Huang, Zhenguang Li, Christina M Leyson, Tanya L Cooper, Simon R Platt, Stephen B Harvey, D Craig Hooper, Milosz Faber, Zhen F Fu

Department of Medical Genetics Faculty Papers

METHODOLOGY/PRINCIPAL FINDINGS: The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and …

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 …

Autologous Hematopoietic Stem Cell Transplantation-10 Years Of Data From A Developing Country, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh

Department of Pathology and Laboratory Medicine

Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 …

Atrial Fibrillation In Sub-Saharan Africa: Epidemiology, Unmet Needs, And Treatment Options, Bruce Sheldon Stambler, Mzee Ngunga

Internal Medicine, East Africa

Health care in Sub-Saharan Africa is being challenged by a double burden of disease as lifestyle diseases common in the developed world, such as stroke and atrial fibrillation (AF), increase, while, simultaneously, health issues of the developing world in terms of communicable disease persist. The prevalence of AF is lower in Africa than in the developed world but is expected to increase significantly over the next few decades. Patients with AF in Africa tend to be younger and have a higher prevalence of rheumatic valvular heart disease than patients with AF in other regions. Permanent AF is the most prevalent …

Meteorological Conditions, Climate Change, New Emerging Factors, And Asthma And Related Allergic Disorders. A Statement Of The World Allergy Organization., Gennaro D'Amato, Stephen T. Holgate, Ruby Pawankar, Dennis K. Ledford, Lorenzo Cecchi, Mona Al-Ahmad, Fatma Al-Enezi, Saleh Al-Muhsen, Ignacio Ansotegui, Carlos E. Baena-Cagnani, David J. Baker, Hasan Bayram, Karl Christian Bergmann, Louis-Philippe Boulet, Jeroen T M Buters, Maria D'Amato, Sofia Dorsano, Jeroen Douwes, Sarah Elise Finlay, Donata Garrasi, Maximiliano Gómez, Tari Haahtela, Rabih Halwani, Youssouf Hassani, Basam Mahboub, Guy Marks, Paola Michelozzi, Marcello Montagni, Carlos Nunes, Jay Jae-Won Oh, Todor A. Popov, Jay M. Portnoy, Erminia Ridolo, Nelson Rosário, Menachem Rottem, Mario Sánchez-Borges, Elopy Sibanda, Juan José Sienra-Monge, Carolina Vitale, Isabella Annesi-Maesano

Manuscripts, Articles, Book Chapters and Other Papers

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of …

Burn Injury Alters The Intestinal Microbiome And Increases Gut Permeability And Bacterial Translocation, Zachary M. Earley, Suhail Akhtar, Stefan J. Green, Ankur Naqib, Omair Khan '15, Abigail R. Cannon, Adam M. Hammer, Niya L. Morris, Xiaoling Li, Joshua M. Eberhardt, Richard L. Gamelli, Richard H. Kennedy, Mashkoor A. Choudhry

Student Publications & Research

Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces …

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Development Of A Biosensor-Based Rapid Urine Test For Detection Of Urogenital Schistosomiasis., Kathleen E Mach, Ruchika Mohan, Shailja Patel, Pak Kin Wong, Michael Hsieh, Joseph C Liao

Urology Faculty Publications

No abstract provided.

Differences In Health-Related Behaviors And Attitudes Between Urban, Rural, And Isolated Households In Western West Virginia, Michael Newsome Phd, Tim Hazelett, Monika Sawhney Phd, Msw

Economics Faculty Research

This study uses data from a 2013 survey of 275 randomly sampled households across nine counties in western West Virginia to examine the significant differences between the health behaviors and attitudes of rural and isolated populations. The results show that age, education, and income are significant factors in explaining differences in health-related behaviors and attitudes for all urban, rural and isolated respondents. However, after controlling for socio-demographic differences, isolation is found to have only a few significant effects, and some of the effects run counter to stereotypes of isolated populations. Rural respondents are significantly more likely than isolated respondents to …

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …

Oncolog, Volume 60, Number 07, July 2015, Kathryn L. Hale, Bryan Tutt, K. Stuyck

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

• Emergency Care for Cancer Patients: Medical problems that may seem routine in patients without cancer often mean something different or have a different cause in cancer patients and may be much more serious, requiring urgent treatment. Managing these problems promptly and effectively is a challenge faced by all cancer centers.
• Immunotherapy Trials Offer Hope to Patients with High-Risk or Metastatic Cancer: Although the cure rate for the breast cancer has risen steadily in recent decades, recurrent or metastatic disease remains difficult to control. To fight metastatic breast cancer and forestall the recurrence of high-risk primary disease, researchers at The University …

Child Marriage Legislation In The Asia-Pacific Region, Elisa Scolaro, Aleksandra Blagojevic, Brigitte Fillion, Venkatraman Chandra-Mouli, Lale Say, Joar Svanemyr, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Child marriage is a human rights violation that robs a girl of her childhood, puts her health, growth, and development at risk, disrupts her education, limits her opportunities for empowerment and social development, and increases her risk of exposure to violence and abuse (for a review of the evidence on the negative effects of child marriage on girls and their children, see Parsons et al. 2015, in this issue). While child marriage is not mentioned specifically in the 1989 Convention on the Rights of the Child (CRC), the Convention does contain a provision requiring governments to abolish “traditional practices prejudicial …

Obesity Early In Adulthood Increases Risk But Does Not Affect Outcomes Of Hepatocellular Carcinoma, Manal M. Hassan, Reham Abdel-Wahab, Ahmed Kaseb, Ahmed Shalaby, Alexandria Phan, Hashem El-Serag, Ernest Hawk, Jeff Morris, Kanwal Pratap Singh Raghav, Ju-Seog Lee, Jean-Nicolas Vauthey, Gehan Bortus, Harrys Torres, Christopher Amos, Robert Wolff, Donghui Li

Dartmouth Scholarship

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC.

Inhaled Nitric Oxide As An Adjunctive Treatment For Cerebral Malaria In Children: A Phase Ii Randomized Open-Label Clinical Trial, Juliet Mwanga-Amumpaire, Ryan W. Carroll, Elisabeth Baudin, Elisabeth Kemigisha, Dorah Nampijjah, Kenneth Mworozi, Data Santorino, Dan Nyehangane, Daniel I. Nathan, Pierre De Beaudrap, Jean-Francois Etard, Martin Feelish, Bernadette O. Fernandez, Annie Berssenbrugge, David Bangsberg, Kenneth D. Bloch, Yap Boum Ii, Warren M. Zapol

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM.

Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment.

Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N₂ for 48 or more hours. Plasma Ang-1 levels …

Role Of Phenol-Soluble Modulins In Formation Of Staphylococcus Aureus Biofilms In Synovial Fluid., Sana S Dastgheyb, Amer E Villaruz, Katherine Y Le, Vee Y Tan, Anthony C Duong, Som S Chatterjee, Gordon Y C Cheung, Hwang-Soo Joo, Noreen J Hickok, Michael Otto

Department of Orthopaedic Surgery Faculty Papers

Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such …