Digital Commons Network^™

Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model, Bing Xu

Wayne State University Dissertations

The aim of this study was to elucidate the expression and functions of interleukin (IL)-24 and suppressor of cytokine signaling 3 (SOCS3), and their regulatory relationship in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by the infection, and this upregulation was dampened by flagellin pretreatment. Time course studies revealed that IL-24 expression was markedly elevated, followed by a subsidence and second elevation, a pattern shared with SOCS3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression, and suppressed SOCS3, IL-1β, IL-1RN, and …

Essays On Healthy Aging From The Perspective Of A Health Production Function, Nasim Baghban Ferdows

Wayne State University Dissertations

This dissertation examines the determinants of healthy aging among older adults using Grossman’s framework of a health production function. Healthy aging is produced using a variety of inputs, including some determined in early life, such as health and socioeconomic status as a child, others determined in young adulthood, such as education, others determined in mid-life, such as household wealth, and still others determined in later-life, such as current health habits. A production function for healthy aging is estimated using nationally representative data from the 2010 Health and Retirement Study on non-institutionalized seniors, and positing a simultaneous equations mediation model, recognizing …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish

Wayne State University Dissertations

Breast cancer is the most common cancer and the second leading

cause of cancer death in women. While ER-positive breast cancer subtypes are initially

well-managed by targeted therapies targeting estrogen signaling, many women are

suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients

who were previously successfully treated with anti-estrogen therapies worsens

overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of

a tumor may allow for the possibility …

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …

Short Communication: Analysis Of Minor Populations Of Human Immunodeficiency Virus By Primer Identification And Insertion-Deletion And Carry Forward Correction Pipelines, Paul Hughes, Wenjie Deng, Scott C. Olson, Robert W. Coombs, Michael Chung, Lisa M. Frenkel

Internal Medicine, East Africa

Accurate analysis of minor populations of drug-resistant HIV requires analysis of a sufficient number of viral templates. We assessed the effect of experimental conditions on the analysis of HIV pol 454 pyrosequences generated from plasma using (1) the ‘‘Insertion-deletion (indel) and Carry Forward Correction’’ (ICC) pipeline, which clusters sequence reads using a nonsubstitution approach and can correct for indels and carry forward errors, and (2) the ‘‘Primer Identification (ID)’’ method, which facilitates construction of a consensus sequence to correct for sequencing errors and allelic skewing. The Primer ID and ICC methods produced similar estimates of viral diversity, but differed in …

Reduction Of Oxidative Stress And Storage Lesions (Rcsl) In Red Blood Cells - Analysis Of Ascorbic Acid (Aa), N-Acetylcysteine Amide (Ad4), And Serotonin (5-Ht), Shanmuka Gadiraju

UROP Posters

Oxidative stress is a common occurrence in red blood cell (RBC) storage in blood banks throughout the world. Typically RBC units stored under routine standard protocol (stored in SAGM-CPD additive solution) can only be kept up to 42 days for transfusion usage before being discarded. I am studying the effects of Ascorbic Acid (AA), N-acetylcysteine amide (AD4), and Serotonin (5-HT) as additives in blood bank storage because I want to find out if these additives can reduce storage-induced oxidative stress on red blood cells (RBCs), in order to help my reader understand how potential blood storage additives can affect the …

Parallel Profiles Of Inflammatory And Effector Memory T Cells In Visceral Fat And Liver Of Obesity-Associated Cancer Patients, Melissa Conroy, Karen Galvin, Suzanne Doyle, Maria Kavanagh, Ann-Marie Mongan, Aoife Cannon, Gillian Moore, John Reynolds, Joanne Lysaght

Articles

In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum …

Methodologies And Considerations For Bladder Cancer Detection With Raman Based Urine Cytology, Laura T. Kerr, Thérése M. Lynn, Ivor M. Cullen, Padraig J. Daly, Nigam Shah, Shirley O'Dea, Alison Malkin, Bryan M. Hennelly

Articles

Bladder cancer has the highest recurrence rate of any cancer. The American Urological Association recommends cystoscopic surveillance every 3–6 months for 3 years, and at least once a year thereafter, particularly for high-risk patients; however, cystoscopy is invasive, expensive, and is not without insignificant morbidity for the patient. Urine cytology is often used as an adjunct to cystoscopy; however, it has a low sensitivity in detecting low grade bladder cancers. Recent studies have investigated the application of Raman micro-spectroscopy for the detection of bladder cancer via urine cytology, and it has been demonstrated to significantly improve the diagnostic sensitivity of …

Novel Therapeutic Approaches To Induce Autophagy In Brain Cancer, Gillian Conway

Doctoral

Glioblastoma Multiforme (GBM) is classified as a malignant grade IV astrocytoma, and is considered to be the most biologically aggressive brain tumour with a 5-year survival rate of ~4%. The most frequent issue arising with GBM tumours is the high level of resistance observed to conventional therapeutic methods i.e. surgery, chemotherapy and radiation, thus signifying the urgency for the development of novel therapeutic methods. This study aims to investigate and develop both a complimentary and novel method to overcome the current treatment barriers. We have investigated the use of novel technologies such as cold atmospheric plasma (CAP) as an alternative …

Diagnostics Of Primary Immunodeficiencies Through Next-Generation Sequencing., Vera Gallo, Laura Dotta, Giuliana Giardino, Emilia Cirillo, Vassilios Lougaris, Roberta D'Assante, Alberto Prandini, Rita Consolini, Emily G. Farrow, Isabelle Thiffault, Carol J. Saunders, Antonio Leonardi, Alessandro Plebani, Raffaele Badolato, Claudio Pignata

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recently, a growing number of novel genetic defects underlying primary immunodeficiencies (PIDs) have been identified, increasing the number of PID up to more than 250 well-defined forms. Next-generation sequencing (NGS) technologies and proper filtering strategies greatly contributed to this rapid evolution, providing the possibility to rapidly and simultaneously analyze large numbers of genes or the whole exome.

OBJECTIVE: To evaluate the role of targeted NGS and whole exome sequencing (WES) in the diagnosis of a case series, characterized by complex or atypical clinical features suggesting a PID, difficult to diagnose using the current diagnostic procedures.

METHODS: We retrospectively analyzed …

Prevalence And Determinants Of Postpartum Depression In A Tertiary Care Hospital, Shiyam Sunder Tikmani, Tufail Soomro, Prashant Tikmani

Community Health Sciences

Purpose: Postpartum depression is one of the common complication of postpartum period and a major public health issue. It adversely affects the mother, her child, and the family. To determine the prevalence and determinants of postpartum depression in women delivered in a tertiary hospital Karachi.
Methods: This was a cross-sectional study carried out in a private hospital of Karachi, from 1^st February 2014 to 31^st January 2016. All women having age between 20-49 years between 4-6 weeks postpartum period consented to participate were included. Women with pre-existing co-morbid like diabetes mellitus, hypertension, physical and psychiatric illnesses, having multigestation …

Initiation And Retention In Couples Outpatient Treatment For Parents With Drug And Alcohol Use Disorders, Abbly L. Braitman, Michelle L. Kelley

Psychology Faculty Publications

The focus of the current study was to identity mental health, relationship factors, substance use related problems, and individual factors as predictors of couples-based substance abuse treatment initiation and attendance. Heterosexual couples with children that met study criteria were invited to attend 12 sessions of outpatient behavioral couples therapy. Men were more likely to initiate treatment if they had a higher income, had greater relationship satisfaction, were initiating treatment for alcohol use disorder only, were younger when they first suspected a problem, and had higher depression but lower hostility or phobic anxiety. Men attended more treatment sessions if they reported …

Incidence And Factors Associated With Nonalcoholic Fatty Liver Disease Among Patients With Rheumatoid Arthritis, Ani K. John

Walden Dissertations and Doctoral Studies

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common hepatic diseases worldwide, making the diagnosis and management of NAFLD an emerging public health issue. Theories associated with NAFLD surmise that inflammation may be the root cause, along with the complex interplay of other chronic conditions such as obesity, metabolic syndrome, diabetes, dyslipidemia, and cardiovascular disease (CVD). It is unknown if other inflammatory conditions such as rheumatoid arthritis (RA), along with the use of methotrexate (MTX), might confer increased risk for NAFLD. Longitudinal data collected from a retrospective cohort of 17,481 adult RA patients in the United States …

Complexity Of Prostate Cancer Diagnosis In African American Men In The United States, Adam B. Sumlin

Walden Dissertations and Doctoral Studies

Researchers have identified higher incidence rates and mortality rates among African American men (AAM) diagnosed with prostate cancer than they have among urban African American men. This quantitative descriptive study was conducted to measure the association between advanced stage and grade of prostate cancer, demographic location, and prostate specific antigen (PSA) levels over a 5-year period in AAM and European American men (EAM) in rural versus urban communities. This study addressed 4 research questions concerning cancer grade, cancer stage, age, geographic location, PSA level, and the impact that each of these variables had on prostate cancer diagnosis in AAM in …

Adding A Single Low-Dose Of Primaquine (0.25 Mg/Kg) To Artemether-Lumefantrine Did Not Compromise Treatment Outcome Of Uncomplicated Plasmodium Falciparum Malaria In Tanzania: A Randomized, Single-Blinded Clinical Trial, Richard Mwaiswelo, Billy Ngasala, Irina Jovel, Berit Aydin‑Schmidt, Roland Gosling, Zul Premji, Bruno Mmbando, Anders Björkman, Andreas Mårtensson

Pathology, East Africa

Background: The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission set‑ tings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

Methods: A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged ≥1 year, …

Safety Of A Single Low-Dose Of Primaquine In Addition To Standard Artemether-Lumefantrine Regimen For Treatment Of Acute Uncomplicated Plasmodium Falciparum Malaria In Tanzania, Richard Mwaiswelo, Billy Ngasala, Irina Jovel, Roland Gosling, Zul Premji, Eugenie Poirot, Bruno Mmbando, Anders Björkman, Andreas Mårtensson

Pathology, East Africa

Background: This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

Methods: Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. …

Cme/Cne Article: A Framework Of Care In Multiple Sclerosis, Part 1, Scott D Newsome, Philip J Aliotta, Jacquelyn Bainbridge, Susan E Bennett, Gary Cutter, Kaylan Fenton, Fred Lublin, Dorothy Northrop, David Rintell, Bryan D Walker, Megan Weigel, Kathleen Zackowski, David E Jones

Faculty, Staff and Student Publications

Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org.

TARGET AUDIENCE: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS).

LEARNING OBJECTIVES: Apply new information about MS to a comprehensive individualized treatment plan for patients with MSIntegrate the team approach into long-term planning in order to optimize rehabilitation care of patients with MSAccreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) …

Genetic And Epigenetic Mechanisms Of Complex Reproductive Disorders, Bhavi P. Modi

Theses and Dissertations

Common, complex disorders are polygenic and multifactorial traits representing interactions between environmental, genetic and epigenetic risk factors. More often than not, contributions of these risk factors have been studied individually and this is especially true for complex reproductive traits where application of genomic technologies has been challenging and slow to progress. This thesis explores the potential of genetic and epigenetic components contributing to a better understanding of the biological pathways underlying disease risk in two specific female complex reproductive traits - polycystic ovary syndrome (PCOS) and preterm premature rupture of membranes (PPROM). The PCOS projects focus on characterization of a …

Eeg Interictal Spike Detection Using Artificial Neural Networks, Howard J. Carey Iii

Theses and Dissertations

Epilepsy is a neurological disease causing seizures in its victims and affects approximately 50 million people worldwide. Successful treatment is dependent upon correct identification of the origin of the seizures within the brain. To achieve this, electroencephalograms (EEGs) are used to measure a patient’s brainwaves. This EEG data must be manually analyzed to identify interictal spikes that emanate from the afflicted region of the brain. This process can take a neurologist more than a week and a half per patient. This thesis presents a method to extract and process the interictal spikes in a patient, and use them to reduce …

Central, Extraventricular And Atypical Neurocytomas: A Clinicopathologic Study Of 35 Cases From Pakistan Plus A Detailed Review Of The Published Literature, Zubair Ahmad, Nasir Ud Din, Aisha Memon, Mohammad Usman Tariq, Romana Idrees, Sheema Hasan

Department of Pathology and Laboratory Medicine

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of 2 % and are designated as "atypical neurocytomas.AIM: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors.MATERIALS AND Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015.Results: Sixty percent of patients were males, and the mean age was 26 …

Sporadic Early Onset Colorectal Cancer In Pakistan: A Case- Control Analysis Of Microsatellite Instability, Sabeehuddin Siddique, Kanwal Tariq, Sobia Rafiq, Ahmed Raheem, Rashida Ahmed, Munira Shabbir-Moosajee, Kulsoom Ghias

Department of Pathology and Laboratory Medicine

Background: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged ≤45 years) with controls (>45 years).
Materials and Methods: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features.
Results: …

Genetic Model, Feifei Zhao, Manshu Song, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

No abstract provided.

Translating Knowledge For Action Against Stroke--Using 5-Minute Videos For Stroke Survivors And Caregivers To Improve Post-Stroke Outcomes: Study Protocol For A Randomized Controlled Trial (Movies4stroke)., Ayeesha Kamran Kamal, Adeel Khoja, Bushra Usmani, Nargis Asad, Asma Ahmed, Iqbal Azam, Sarah Saleem, Saleem Sayani

Department of Medicine

Background: Two thirds of the global mortality of stroke is borne by low and middle income countries (LMICs). Pakistan is the world’s sixth most populous country with a stroke-vulnerable population and is without a single dedicated chronic care center. In order to provide evidence for a viable solution responsive to this health care gap, and leveraging the existing >70 % mobile phone density, we thought it rational to test the effectiveness of a mobile phone-based video intervention of short 5-minute movies to educate and support stroke survivors and their primary caregivers.

Methods: Movies4Stroke will be a randomized control, outcome assessor …

Dysfunctional Epileptic Neuronal Circuits And Dysmorphic Dendritic Spines Are Mitigated By Platelet-Activating Factor Receptor Antagonism, Alberto E. Musto, Robert F. Rosencrans, Chelsey P. Walker, Surjyadipta Bhattacharjee, Chittalsinh M. Raulji, Ludmila Belayev, Zhide Fang, William C. Gordon, Nicolas G. Bazan

Journal Articles: Pediatrics

Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array …

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

A Review Of Factors Contributing To The Shortage Of Palliative Care Service For Adolescent And Young Adult Oncology Patients, Erin K. Harper

Antioch University Dissertations & Theses

Adolescent and young adult oncology (patients aged 15–39 years old) is an emerging group of patients that are recognized to have distinctive qualities concerning their cancer treatment, including intensified psychosocial needs compared to their adult and child counterparts (Bleyer, 2012). The quality of life for adolescent and young adults during and after cancer treatment is disproportionally worse than what is reported by adults and children and the incidence of cancer in this population is steadily growing (Bleyer, 2011, 2012; Pritchard, Cuvelier, Harlos, & Barr, 2011; Rosenberg & Wolfe, 2013; Siegel, Naishadham, & Jemal, 2013; Wein, Pery, & Zer, 2011). Palliative …

Evaluation Of The Uptake And Impact Of Neonatal Vitamin A Supplementation Delivered Through The Lady Health Worker Programme On Neonatal And Infant Morbidity And Mortality In Rural Pakistan: An Effectiveness Trial, Sajid Soofi, Shabina Ariff, Kamran Sadiq, Atif Habib, Zaid Bhatti, Imran Ahmad, Masawar Hussain, Nabeela Ali, Simon Cousens, Zulfiqar A Bhutta

Department of Paediatrics and Child Health

Background: Despite evidence for the benefits of vitamin A supplementation (VAS) among children 6 to 59 months of age, the feasibility of introduction and potential benefit of VAS in the neonatal period in public health programmes is uncertain. Objective: The primary objective was to evaluate the feasibility and effectiveness of early neonatal VAS (single dose of 50 000 international units within 48–72 hours after birth) delivered through the public sector Lady Health Worker (LHW) programme in rural Pakistan and to document its association with a reduction in mortality at 6 months of age.
Methods: A community-based, cluster randomised, …

Decline In Ethical Concerns About Reproductive Technologies Among A Representative Sample Of Us Women, Arthur L. Greil, Kathleen S. Slauson-Blevins, Karina M. Shreffler, Katherine M. Johnson, Michele Lowry, Andrea R. Burch, Julia Mcquillan

Department of Sociology: Faculty Publications

Public awareness and utilization of assisted reproductive technology has been increasing, but little is known about changes in ethical concerns over time. The National Survey of Fertility Barriers, a national, probability-based sample of US women, asked 2031 women the same set of questions about ethical concerns regarding six reproductive technologies on two separate occasions approximately 3 years apart. At Wave 1 (2004–2007), women had more concerns about treatments entailing the involvement of a third party than about treatments that did not. Ethical concerns declined between Wave 1 and Wave 2, but they declined faster for treatments entailing the involvement of …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …