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Histone Deacetylases As Targets For Melanoma Immunotherapy, David Michael Woods

USF Tampa Graduate Theses and Dissertations

Cancer represents the second leading cause of death in the United States. For many malignancies, currently available treatment options offer little long-lasting survival benefits to patients. However, recent studies have shown immunotherapeutic approaches to be an attractive strategy to cancer treatment. While many current immunotherapeutic strategies convey durable responses, such responses are only seen in a minority of patients. An increased understanding of the mechanisms governing tumor immunogenicity and the biology of immune responses is crucial to improving upon the efficacy of current and future cancer immunotherapies. Histone deacetylases (HDACs), enzymes classically associated with regulation of gene expression, have been …

Parallel Ngo Networks For Hiv Control: Risks And Opportunities For Ngo Contracting., Shehla Zaidi, Xaher Gul, Noureen Aleem Nishtar

Community Health Sciences

Policy measures for preventive and promotive services are increasingly reliant on contracting of NGOs. Contracting is a neo-liberal response relying on open market competition for service delivery tenders. In contracting of health services a common assumption is a monolithic NGO market. A case study of HIV control in Pakistan shows that in reality the NGO market comprises of parallel NGO networks having widely different service packages, approaches and agendas. These parallel networks had evolved over time due to vertical policy agendas. Contracting of NGOs for provision of HIV services was faced with uneven capacities and turf rivalries across both NGO …

Successful Identification Of Pathogens By Polymerase Chain Reaction (Pcr)-Based Electron Spray Ionization Time-Of-Flight Mass Spectrometry (Esi-Tof-Ms) In Culture-Negative Periprosthetic Joint Infection., Christina L Jacovides, Rachael Kreft, Bahar Adeli, Bryan Hozack, Garth D Ehrlich, Javad Parvizi

Rothman Institute Papers

BACKGROUND: The diagnosis of periprosthetic joint infection poses many challenges, one of which is the difficulty of isolating the infecting organism. Recently, a sophisticated modality (the Ibis Biosciences T5000 biosensor system) has been introduced that uses pan-domain primers in a series of polymerase chain reactions (PCRs) to identify and speciate essentially all bacteria and fungi as well as to identify key antibiotic resistance genes. We investigated the role of the Ibis in identifying infecting organisms in cases of known and suspected periprosthetic joint infection.

METHODS: Synovial fluid specimens were collected prospectively from eighty-two patients undergoing eighty-seven arthroplasty procedures (sixty-five knee …

Fluoroquinolone And Macrolide Co-Resistance In Clinical Isolates Of Campylobacter Species: A 15-Year Study In Karachi, Pakistan, Seema Irfan, A Ahmad, D Guhar, E Khan, Fasial Malik, Syed Mahmood, Afia Zafar

Department of Pathology and Laboratory Medicine

Fluoroquinolone and macrolide antibiotics are generally considered as first-line drugs for the treatment of severe campylobacteriosis. This study was conducted to analyse the trend of erythromycin and ofloxacin resistance among Campylobacter spp. isolated from stool specimens over a period of 15 years (1992-2007) at The Aga Khan University clinical laboratory in Karachi, Pakistan. A total of 83 396 stool specimens were processed, with a 14% isolation rate for enteric pathogens. The isolation rate of Campylobacter spp. was low during 1992-93 (6%-13%), peaked in 1996 (46%), then ranged from 20% to 40%. We report a rising trend in ofloxacin resistance, re-emergence …

Neuropsychological Outcomes In Adults Commencing Highly Active Anti-Retroviral Treatment In South Africa: A Prospective Study, John Joska, John Joska, Jennifer Westgarth-Taylor, Jacqueline Hoare, Kevin Thomas, Robert Paul, Landon Myer, Dan Stein

Psychology Faculty Works

BackgroundInfection with HIV may result in significant neuropsychological impairment, especially in late stage disease. To date, there have been no cohort studies of the impact of highly active anti-retroviral treatment (HAART) in South Africa where clade C HIV is predominant.MethodsParticipants in the current study were recruited from a larger study of HIV-associated neurocognitive disorders (HAND) and included a group of individuals commencing HAART (n = 82). Baseline and one-year neuropsychological function was assessed using a detailed battery, and summary global deficit scores (GDS) obtained. Associations with change in GDS were calculated.ResultsParticipants had a median CD4 cell count of 166 at …

Twice-Daily Application Of Hiv Microbicides Alters The Vaginal Microbiota, Jacques Ravel, Pawel Gajer, Li Fu, Christine K. Mauck, Sara S.K. Koenig, Joyce Sakamoto, Alison A. Motsinger-Reif, Gustavo F. Doncel, Steven L. Zeichner

Pediatrics Faculty Publications

Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 …

Emil Theodor Kocher, M.D., And His Nobel Prize (1841-1917)., Zhi Ven Fong, B.S., Ernest L. Rosato, Md, Harish Lavu, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

Major contributions to the advancement of surgery occurred at the turn of the 20th century. Theodor Billroth was in the midst of revolutionizing abdominal surgery, whereas Louis Pasteur and Joseph Lister were making landmark strides in antisepsis, forever changing the foundations of surgical thinking. Undoubtedly, Theodor Kocher’s (Fig. 1) exposure to these and other giants had a major influence on his career and contributed to his success and ascent as the first, and one of only 10, surgeons ever to be awarded the Nobel Prize in Medicine.

Uchunguzi (Journal Watch/Montre De Journal) December 2012, Benjamin Wachira

Family Medicine, East Africa

Uchunguzi means investigation in Swahili and provides a summary of some of the most recent international literature as presented in other leading journals, but with an emphasis on what is relevant to our continent.

Labrad : Vol 38, Issue 2 - December 2012, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Automation in Microbiology Specimen Processing and Inoculation
• Use of Automated Urine Analyzer for Urinanalysis
• Automation in Blood Culture
• Vitek 2 System: An Automated System for Antimicrobial Susceptibility Testing
• TB Diagnosis-A New Horizon
• Serological and Molecular Diagnosis of Malaria
• Diagnosis of Leishmaniasis
• Rapid Detection of Dengue NS1 Antigen by ELISA in Suspected Dengue Patients
• Saline Infusion Hysterosonography to Evaluate Abnormal Uterine Bleeding
• Workshop on “Diagnosis of Fungal Infections in Clinical Laboratory”

Influence Of Body Mass Index And Antibiotic Dose On The Risk Of Surgical Site Infections In Pediatric Clean Orthopedic Surgery., Jeffrey J Cies, Shannon Chan, Jobayer Hossain, B Randall Brenn, M Cecilia Di Pentima

Department of Anesthesiology Faculty Papers

OBJECTIVE: To evaluate body mass index (BMI) and antimicrobial dose as risk factors for surgical site infections in pediatric patients.

PATIENTS AND METHODS: Children between 2 and 19 years of age undergoing clean orthopedic procedures and receiving at least one dose of perioperative antibiotics (cefazolin, vancomycin, or clindamycin) were studied. The retrospective case-controlled study was conducted at the Alfred I. duPont Hospital for Children, a 180-bed tertiary-care academic pediatric hospital in Wilmington, DE. Data were collected from January 1, 2002, to December 31, 2005.

RESULTS: Underweight children had a higher risk for SSIs than overweight and normal-weight children. American Society …

Antiseptics And Disinfectants For The Treatment Of Bacterial Vaginosis: A Systematic Review, Hans Verstraelen Verstraelen, Rita Verhelst, Kristien Roelens, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: The study objective was to assess the available data on efficacy and tolerability of antiseptics and disinfectants in treating bacterial vaginosis (BV).

Methods: A systematic search was conducted by consulting PubMed (1966-2010), CINAHL (1982-2010), IPA (1970-2010), and the Cochrane CENTRAL databases. Clinical trials were searched for by the generic names of all antiseptics and disinfectants listed in the Anatomical Therapeutic Chemical (ATC) Classification System under the code D08A. Clinical trials were considered eligible if the efficacy of antiseptics and disinfectants in the treatment of BV was assessed in comparison to placebo or standard antibiotic treatment with metronidazole or clindamycin …

Prevalence And Antimicrobial Agent Susceptibility Of Methicillin-Resistant Staphylococcus Aureus In Healthy Pediatric Outpatients In Las Vegas, Echezona E. Ezeanolue, Mark P. Buttner, Patricia Cruz, Joanne L. Henry, Chad L. Cross, Linda D. Stetzenbach

Nevada Journal of Public Health

Colonization and infection by community-associated resistant strains of Staphylococcus aureus are being reported in epidemic proportions. The purpose of this study was to determine the local prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization in children and to characterize the MRSA isolates in the laboratory with regard to antimicrobial agent susceptibility patterns, and the presence of the mecA and the Panton-Valentine leukocidin (PVL) genes. Nasal swabs were collected at two pediatric clinics from a total of 505 children during health maintenance visits. A brief questionnaire was administered to collect demographic data and pertinent medical, family, and social history. Samples were cultured …

T-Cell Activation Is Enhanced By Targeting Il-10 Cytokine Production In Toll-Like Receptor-Stimulated Macrophages, Ryan Walk, Steven Elliott, Felix C. Blanco, Jason A. Snyder, Ashley M. Jacobi, Scott Rose, Mark Behlke, Aliasger Salem, Stanislav Vukmanovic, Anthony D. Sandler

Surgery Faculty Publications

Toll-like receptor (TLR) agonists represent potentially useful cancer vaccine adjuvants in their ability to stimulate antigen-presenting cells (APCs) and subsequently amplify the cytotoxic T-cell response. The purpose of this study was to characterize APC responses to TLR activation and to determine the subsequent effect on lymphocyte activation. We exposed murine primary bone marrow-derived macrophages to increasing concentrations of agonists to TLRs 2, 3, 4, and 9. This resulted in a dose-dependent increase in production of not only tumor necrosis factor–alpha (TNF-α), a surrogate marker of the proinflammatory response, but also interleukin 10 (IL-10), a well-described inhibitory cytokine. Importantly, IL-10 secretion …

Barriers To The Effective Implementation Of Immunization Information Systems In A Private Provider Setting, Echezona E. Ezeanolue, Ineada Jack, William Downey, Benjamin Hart, Chad L. Cross

Nevada Journal of Public Health

One of the goals of Healthy People 2010 is to increase the proportion of children less than 6 years of age with two or more vaccinations recorded in a fully operational population-based immunization information system to 95%. In 2008, we piloted the Nevada web-based immunization information system (WEBIZ) in a large private pediatric clinic in north-west Las Vegas. Our objectives were: (1) to determine compliance with the recommendation that all vaccine providers report immunization activities to the WEBIZ without a state mandate and (2) to determine perceived barriers to compliance and suggestions on how to overcome expressed barriers. We documented …

A Case Of A Male With Fever And Fatigue, Steve Ting

The Medicine Forum

This is a case of a 78 year old Caucasian gentleman who presented to the hospital in the early summer with complaints of high fevers and progressive fatigue. The patient lives near Philadelphia and enjoys doing yard work. He reported finding a tick attached to the skin near his groin approximately 3 weeks prior to admission. The tick was removed; however the patient was unsure of the duration of the tick attachment. He also denied developing any significant rash in that area. He had no recent sick contacts and no recent history of travel. He began developing fever spikes up …

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Prevalence And Determinants Of Human Papillomavirus Infection And Cervical Lesions In Hiv-Positive Women In Kenya, H De Vuyst, N R. Mugo, M H. Chung, K P. Mckenzie, E Nyongesa-Malava, V Tenet, J W. Njoroge, S R. Sakr, C Jlm Meijer, P Jf Snijders, Farzana Rana, S Franceschi

Pathology, East Africa

Background: We assessed the association of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) with various characteristics, CD4 count and use of combination antiretroviral therapy (cART) among HIV-positive women.

Methods: Cross-sectional study of 498 HIV-positive women who underwent HPV PCR-based testing, cytology, and systematic cervical biopsy.

Results: In all, 68.7% of women were HPV-positive, 52.6% had high-risk (hr) HPV, and 40.2% multiple type infections. High-risk human papillomavirus-positivity did not vary significantly by age but it was negatively associated with education level. The most frequent types in 113 CIN2/3 were HPV16 (26.5%), HPV35 (19.5%), and HPV58 (12.4%). …

Clostridium Septicum Growth From A Total Knee Arthroplasty Associated With Intestinal Malignancy: A Case Report, Demetri M. Economedes, Jerome Santoro, Carl A. Deirmengian

PCOM Scholarly Works

BACKGROUND: Previous reports of infection with Clostridium septicum have identified an unexpected association with concurrent malignancy. The reported rate of associated malignancy has been found to be as high as 81 percent. The purpose of this case report was to present a case of a total knee arthroplasty infected with C. septicum and the subsequent finding of an occult colonic malignancy.

CASE PRESENTATION: A 74 year-old man underwent uneventful bilateral total knee arthroplasties. Two weeks post-operatively, he presented with acute swelling, redness and pain of the left knee. Aspiration of the knee was sent for cell count and …

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, …

Gene Expression In Human Accessory Lacrimal Glands Of Wolfring, John L. Ubels, Ilene K. Gipson, Sandra J. Spurr-Michaud, Ann S. Tisdale

University Faculty Publications and Creative Works

The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. METHODS: Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. RESULTS: Of the 24 most highly expressed genes, 9 were …

Gene Expression In Human Accessory Lacrimal Glands Of Wolfring, John L. Ubels, Ilene K. Gipson, Sandra J. Spurr-Michaud, Ann S. Tisdale

University Faculty Publications and Creative Works

PURPOSE: The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. METHODS: Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. RESULTS: Of the 24 most highly expressed genes, 9 …

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 …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

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 …

The Causes, Treatment, And Outcome Of Acute Heart Failure In 1006 Africans From 9 Countries, Albertino Damasceno, Bongani M. Mayosi, Mahmoud Sani, Okechukwu S. Ogah, Charles Mondo, Dike Ojji, Anastase Dzudie, Charles Kouam Kouam, Ahmed Suliman, Neshaad Schrueder, Gerald Yonga, Serigne Abdou Ba, Fikru Maru, Bekele Alemayehu, Christopher Edwards, Beth A. Davison, Gad Cotter, Karen Sliwa

Internal Medicine, East Africa

Background: Acute heart failure (AHF) in sub-Saharan Africa has not been well characterized. Therefore,wesought to describe the characteristics, treatment, and outcomes of patients admitted with AHF in sub-Saharan Africa.

Methods: The Sub-Saharan Africa Survey of Heart Failure (THESUS–HF) was a prospective, multicenter, observational survey of patients with AHF admitted to 12 university hospitals in 9 countries. Among patients presenting with AHF, we determined the causes, treatment, and outcomes during 6 months of follow-up.

Results: From July 1, 2007, to June 30, 2010, we enrolled 1006 patients presenting with AHF. Mean (SD) age was 52.3 (18.3) years, 511 (50.8%) were women, …

Non Fatal Injuries Among Infants: A Pilot Study, Seema Zainulabdin Lasi, Ghazala Rafique, Habib Peermohammad

Human Development Programme

Objective: To determine the incidence, nature and the extent of infant injuries in two suburban and rural communities of Pakistan.
Methods: The cross-sectional study was conducted on a cohort of 310 infants in suburban and rural communities of Pakistan in September 2007. The information was collected from primary care-givers based on any injury that had occurred to their infants during the preceding 3 months that required treatment at home or in a hospital.
Result: The incidence of non-fatal injury for infants up to 1-year-old was found to be 19 injuries per 100 person (child) years of exposure (95% CI 9.90 …

Common Respiratory Issues In Ambulatory Obstetrics., Kelly M Orzechowski, Richard C Miller

Department of Obstetrics and Gynecology Faculty Papers

This article reviews the diagnosis and management of the most common respiratory conditions complicating pregnancy--asthma and influenza. We also review strategies for smoking cessation in pregnancy as, in addition to exacerbating all other pulmonary conditions, smoking is the most modifiable risk factor for poor pregnancy outcome. Moreover, the obstetrician frequently encounters each of these conditions in the ambulatory setting. A thorough knowledge of the normal pregnancy-induced physiological respiratory changes combined with a comprehensive understanding of how to manage these conditions, will provide the obstetrician with the armamentarium needed to optimize health outcomes for mothers and their fetuses.

Triple Valve Endocarditis By Mycobacterium Tuberculosis: A Case Report., Quratulain Shaikh, Syed Faisal Mahmood

Department of Medicine

BACKGROUND:

Granulomas caused by Mycobacterium Tuberculosis have been observed at autopsy in the heart, pre-dominantly in the myocardium and endocardium, but rarely involving the coronary vessels and valvular structures. Mycobacterium tuberculosis valvular endocarditis is extremely rare, with most reports coming from autopsy series.

CASE PRESENTATION:

We report the case of a 17 year old immunocompetent girl who presented with history of fever, malaise, foot gangrene and a left sided hemiparesis. On investigation she was found to have infective endocarditis involving the aortic, mitral and tricuspid valves. She had developed a right middle cerebral artery stroke. She underwent dual valve replacement …

Fulminant Invasive Aspergillosis Of The Mediastinum In An Immunocompetent Host: A Case Report., Muhammad Tariq Shakoor, Samia Ayub, Zunaira Ayub, Syed Faisal Mahmood

Department of Medicine

Introduction: Invasive aspergillosis is a serious complication in immunocompromised patients. It is an opportunistic disease, which predominantly occurs in the lungs, although dissemination to virtually any organ is possible. Invasive aspergillosis in an immunocompetent patient with extension to the mediastinum has rarely been reported. Here, we present the case of a patient with no apparent immunodeficiency state, who presented with Aspergillus endocarditis and fulminant invasive aspergillosis with extensive involvement of the mediastinal structures, which ultimately was responsible for her death. To the best of our knowledge, this is the first reported case in the literature on fulminant invasive mediastinal aspergillosis …

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 …