Medicine and Health Sciences Commons^™

Identification Of Novel Therapeutic Small-Molecule Inhibitors Of Dna Double-Stranded Break Repair, Vikram Jairam

Yale Medicine Thesis Digital Library

Mammalian cells mainly utilize two DNA repair pathways to repair double stranded breaks (DSB): homologous recombination (HR) and non-homologous end joining (NHEJ). While HR utilizes homologous DNA sequences as a template for repair, NHEJ processes and re-ligates the ends of the breaks. NHEJ is further sub-divided into a DNA-PK-dependent canonical pathway, and alternative pathways, which are more mutagenic. These pathways are essential for cell survival after ionizing radiation, and thus have become important therapeutic targets for radiosensitization. Our group recently performed multiple high-throughput small molecule screens for novel DSB repair inhibitors. These studies identified numerous selective NHEJ and HR inhibitors, …

The Danger Zone: How The Dangerousness Standard In Civil Commitment Proceedings Harms People With Serious Mental Illness, Sara Gordon

Scholarly Works

Almost every American state allows civil commitment upon a finding that a person, as a result of mental illness, is gravely disabled and unable to meet their basic needs for food and shelter. Yet in spite of these statutes, most psychiatrists and courts will not commit an individual until they are found to pose a danger to themselves or others. All people have certain rights to be free from unwanted medical treatment, but for people with serious mental illness, those civil liberties are an abstraction, safeguarded for them by a system that is not otherwise ensuring access to shelter and …

Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney

PCOM Biomedical Studies Student Scholarship

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H₂O₂). Endothelial-derived NO can be significantly reduced by increased SO/H₂O₂ in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …

Effects Of Hormonal Withdrawal On Prostate Cancer Progression, Jacqueline Chakrya So

PCOM Biomedical Studies Student Scholarship

Prostate cancer, or prostatic carcinoma (PrCa), is the second leading cause of cancer-related deaths in men in the Western world. One in seven men are expected to be diagnosed with the disease in the United States. Suppressing androgen/androgen receptor pathway is a first-line therapeutic treatment known as Androgen Deprivation Therapy (ADT). Most patients respond well to ADT, but an overwhelming majority of PrCa progress to an advanced stage of PrCa independent of hormone, known as Castration Resistant Prostate Cancer (CRPC). There is currently no known cure for CRPC. In this study, the androgensensitive LNCaP cells served as an in vitro …

Investigating The Roles Of Zinc-Binding Protein (Zbp-89) And Rela (Nfkb-P65) In The Regulation Of Matrix Metalloproteinase 1 (Mmp1) Gene Expression, Nelly Khaselev

PCOM Biomedical Studies Student Scholarship

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases with the unique ability to breakdown virtually the entire extracellular matrix (ECM). Through ECM remodeling, MMPs play an important role in normal development, tissue repair, angiogenesis, and apoptosis. Studies have shown that unregulated MMP expression plays a role in many cancers and chronic inflammatory diseases. Previous research has used gene sequence analysis ofthe MMP-1 promoter to identify a putative ZBP-89 binding site at -1969 bp. Chromatin immuneprecipitation experiments showed that both ZBP-89 and Re!A (p65) could bind to this binding site. In this thesis research, transfection experiments were used to explore …

Testing Multi-Theory Model (Mtm) In Predicting Initiation And Sustenance Of Physical Activity Behavior Among College Students, Vinayak K. Nahar, Manoj Sharma, Hannah Priest Catalano, Melinda J. Ickes, Paul Johnson, M. Allison Ford

Kinesiology and Health Promotion Faculty Publications

Background: Most college students do not adequately participate in enough physical activity (PA) to attain health benefits. A theory-based approach is critical in developing effective interventions to promote PA. The purpose of this study was to examine the utility of the newly proposed multi-theory model (MTM) of health behavior change in predicting initiation and sustenance of PA among college students.

Methods: Using a cross-sectional design, a valid and reliable survey was administered in October 2015 electronically to students enrolled at a large Southern US University. The internal consistency Cronbach alphas of the subscales were acceptable (0.65-0.92). Only those who did …

Specificity Of The Minimal Clinically Important Difference Of The Quick Disabilities Of The Arm Shoulder And Hand (Qdash) For Distal Upper Extremity Conditions, Enrique V. Smith-Forbes, Dana M. Howell, Jason Willoughby, Donald G. Pitts, Timothy L. Uhl

Physical Therapy Faculty Publications

Retrospective cohort design. The minimal clinically important difference (MCID) for the quick Disabilities of the Arm, Shoulder and Hand (QDASH) has been established using a pool of multiple conditions, and only exclusively for the shoulder. Understanding diagnoses-specific threshold change values can enhance the clinical decision-making process. Before and after QDASH scores for 406 participants with conditions of surgical distal radius fracture, non-surgical lateral epicondylitis, and surgical carpal tunnel release were obtained. The external anchor administered at each fourth visit was a 15-point global rating of change scale. The test-retest reliability of the QDASH was moderate for all diagnoses: intraclass correlation …

The Impact Of The Introduction Of The Pecarn Head Ct Rules On The Utilisation Of Head Ct Scans For Children With Mild Head Injury At The Aga Khan University Hospital, Nairobi., Isaac Oluoch Kobe

Master of Medicine in General Surgery

Background: Head injury is the most common cause of childhood morbidity and mortality worldwide. Mild head injury comprises 90% of cases of head injury in children. Head CT scans are few, expensive and have the side effect of ionizing radiation whose effect is potentiated in children and also associated risk of sedation that is often required when doing CT scans in young children. The decision to order CT scans of the head is thus made on the basis of clinical decision rules of which the PECARN CT head rule has been found to be most sensitive and useful. Objectives: Primary: …

Evidence And Evidence Gaps In Adolescent Health, George Patton, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

The momentum to bring adolescents and young adults to center stage in global health and international development is palpable. Adolescents are increasingly seen as a crucial group for the success of the newly adopted Agenda for Sustainable Development [1]. Sitting within the Agenda for Sustainable Development framework, the 2030 Global Strategy for Women's, Children's and Adolescents' Health has extended the Every Woman, Every Child agenda to adolescence [2]. The strategy articulates the need for adolescent responsive health systems as well as social determinants, a focus that extends to legal and policy environments [3]. Countries seeking to adopt this more holistic …

Moving Towards The Goals Of Fp2020 — Classifying Contraceptives, Mario Philip R. Festin, James Kiarie, Julie Solo, Jeffrey Spieler, Shawn Malarcher, Paul F.A. Van Look, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

With the renewed focus on family planning, a clear and transparent understanding is needed for the consistent classification of contraceptives, especially in the commonly used modern/traditional system. The World Health Organization Department of Reproductive Health and Research and the United States Agency for International Development (USAID) therefore convened a technical consultation in January 2015 to address issues related to classifying contraceptives. The consultation defined modern contraceptive methods as having a sound basis in reproductive biology, a precise protocol for correct use and evidence of efficacy under various conditions based on appropriately designed studies. Methods in country programs like Fertility Awareness …

Eregistries: Electronic Registries For Maternal And Child Health, J. Frederik Frøen, Sonja L. Myhre, Michael J. Frost, Doris Chou, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: The Global Roadmap for Health Measurement and Accountability sees integrated systems for health information as key to obtaining seamless, sustainable, and secure information exchanges at all levels of health systems. The Global Strategy for Women’s, Children’s and Adolescent’s Health aims to achieve a continuum of quality of care with effective coverage of interventions. The WHO and World Bank recommend that countries focus on intervention coverage to monitor programs and progress for universal health coverage. Electronic health registries - eRegistries - represent integrated systems that secure a triple return on investments: First, effective single data collection for health workers to …

Use Of A Web-Based Dietary Assessment Tool In Early Pregnancy, Laura Mullaney, Amy C. O'Higgins, Shona Cawley, R. Kennedy, Daniel Mccartney, M.J. Turner

Articles

Background Maternal diet is critical to fetal development and lifelong health outcomes. In this context, dietary quality indices in pregnancy should be explicitly underpinned by data correlating food intake patterns with nutrient intakes known to be important for gestation.

Aims Our aim was to assess the correlation between dietary quality scores derived from a novel online dietary assessment tool (DAT) and nutrient intake data derived from the previously validated Willett Food Frequency Questionnaire (WFFQ).

Methods 524 women completed the validated semiquantitive WFFQ and online DAT questionnaire in their first trimester. Spearman correlation and Kruskal–Wallis tests were used to test associations …

The Effectiveness Of A Group Motor Skill Intervention Program In Children With Developmental Coordination Disorder: Program Frequency Matters., Priscila M. Caçola, Melvin Ibana, Michael Romero, Jennifer Chuang

Internet Journal of Allied Health Sciences and Practice

Purpose: The purpose of this study was to investigate the effects of two group programs on visual-motor integration, motor proficiency, gross-motor skills, and parental perception of motor difficulties in children with developmental coordination disorder (DCD). We compared whether the frequency of two programs (10 one hour sessions - once/week for 10 weeks verses 24 one hour sessions – twice/week for 12 weeks) produced different changes in motor skills. Methods: Children in the two programs were assessed before and after each program with the MABC-2, DCD-Q, BOT-2, Beery-VMI-6, and the TGMD-2 assessments. The emphasis of the programs was on group activities …

Students' Perspectives On Online And Face-To-Face Components Of A Blended Course Design In Health And Kinesiology At A South Western Public University In The Usa, Wycliffe W. Njororai Simiyu, Fletcher J. Njororai, Tejaswini Chanumolu

Health & Kinesiology Faculty Publications and Presentations

Introduction: The current higher education environment in the United States of America (USA) and worldwide is focused on providing people an opportunity to access a quality education at a competitive price and one that is flexible enough to meet the needs of a diverse student demographic. It is therefore necessary for course delivery methods to accommodate these diverse needs without sacrificing rigor necessary for accreditation due to the diverse backgrounds, occupations, and time constraints of students in today’s environment Purpose: The purpose of this study was to establish the students’ perception of the online and face-to-face components of a blended …

Walkability In Upper East Texas Cities And Implications For Physical Activity And Health, Wycliffe W. Njororai Simiyu, Fletcher J. Njororai, Billystrom Aronya Jivetti

Health & Kinesiology Faculty Publications and Presentations

Introduction: Physical activity is an important intervention strategy against the increasing cases of overweight and obesity in the USA and many other parts of the world. Walking has been identified as a component of physical activity that can easily be incorporated into one’s lifestyle. Recent studies on physical activity have focused on promoting walking as a health enhancing endeavor. Purpose: This study examined the walkability of the environments in 57 cities drawn from 22different counties in upper east Texas within the USA. Methods and materials: The data for all the 57 key cities in upper east Texas were collected from …

Cytotoxic And Mutagenic Potential Of Solutions Exposed To Cold Atmospheric Plasma, Daniela Boehm, Caitlin Heslin, P.J. Cullen, Paula Bourke

Articles

The exposure of aqueous solutions to atmospheric plasmas results in the generation of relatively long-lived secondary products such as hydrogen peroxide which are biologically active and have demonstrated anti-microbial and cytotoxic activity. The use of plasma-activated solutions in applications such as microbial decontamination or anti-cancer treatments requires not only adequate performance on target cells but also a safe operating window regarding the impact on surrounding tissues. Furthermore the generation of plasma-activated fluids needs to be considered as a by-stander effect of subjecting tissue to plasma discharges. Cytotoxicity and mutagenicity assays using mammalian cell lines were used to elucidate the effects …

The Microenvironment Of Visceral Adipose Tissue And Liver Alter Natural Killer Cell Viability And Function, Melissa J. Conroy, Vivienne Fitzgerald, Suzanne Doyle, Shauna Channon, Zivile Useckaite, Niamh Gilmartin, Cliona O'Farrelly, Narayanasamy Ravi, John V. Reynolds, Joanne Lysaght

Articles

The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly …

Potassium Intake, Bioavailability, Hypertension, And Glucose Control, Michael S. Stone, Lisa Martyn, Connie M. Weaver

Articles

Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of potassium across the cell membrane determines cellular membrane potential, which is maintained in large part by the ubiquitous ion channel the sodium-potassium (Na+-K+) ATPase pump. Approximately 90% of potassium consumed (60-100 mEq) is lost in the urine, with the other 10% excreted in the stool, and a very small amount lost in sweat. Little is known about the bioavailability of potassium, especially from dietary sources. Less is understood on how bioavailability may affect …

E-Cigarettes: Effective Cessation Tools Or Public Health Threat?, Luke Clancy, Kate Babineau

Articles

In a short time, electronic cigarettes have become a multi-billion dollar industry. Since their introduction to the market, prevalence of ever-use among smokers in the USA appears to have increased from 2% in 2010 to >30% in 2012, and the rate of increase appears to be similar in the United Kingdom, Ireland and other Western countries according to a special Eurobarometer survey in 2014.1 The e-cigarette market is estimated to be worth over $3 billion. However, there is no consensus on the role of e-cigarettes and their contribution to the provision of smoking cessation (SC) services, nor to global tobacco …

Hospital Utilisation In Indigenous And Non-Indigenous Infants Under 12 Months Of Age In Western Australia, Prospective Population Based Data Linkage Study, Kimberley Mcauley, Daniel Mcaullay, Natalie A. Strobel, Rhonda Marriott, David N. Atkinson, Julia V. Marley, Fiona J. Stanley, Karen M. Edmond

Research outputs 2014 to 2021

Background:

Indigenous infants (infants aged under 12 months) have the highest hospital admission and emergency department presentation risks in Australia. However, there have been no recent reports comparing hospital utilisation between Indigenous and non-Indigenous infants.

Methods:

Our primary objective was to use a large prospective population-based linked dataset to assess the risk of all-cause hospital admission and emergency department presentation in Indigenous compared to non-Indigenous infants inWestern Australia (WA). Secondary objectives were to assess the effect of socio-economic status (Index of Relative Socio-Economic Disadvantage [IRSD]) on hospital utilisation and to understand the causes of hospital utilisation.

Findings:

There were 3,382 …

Rickettsia Felis, Transmission Mechanisms Of An Emerging Flea-Borne Rickettsiosis, Lisa Diane Brown

LSU Doctoral Dissertations

Rickettsia felis is an emerging insect-borne rickettsial pathogen and the causative agent of flea-borne spotted fever. First described as a human pathogen from the United States in 1991, R. felis is now identified throughout the world and considered a common cause of fever in Africa. The cosmopolitan distribution of this pathogen is credited to the equally widespread occurrence of cat fleas (Ctenocephalides felis), the primary vector and reservoir of R. felis. Additionally, R. felis has been identified in other hematophagous arthropods (including numerous species of fleas, ticks, mosquitoes, and mites). Most transmission cycles of pathogenic Rickettsia include transovarial and transstadial …

Looking Into Malaria, Ahmad Ahmad

A with Honors Projects

According to the Centers for Disease Control, malaria has been a concern for more than 4000 years, with symptoms being described in ancient medical writings, and remains a prevalent health concern. In this student paper, the author reports on the history of the disease, it's epidemiology, diagnosis and treatment.

Student Reflections Of Psychiatric/Mental Health: Using Journals And Creative Expressions, Melinda Hermanns, Barbara K. Haas

Nursing Faculty Publications and Presentations

Second semester undergraduate nursing students in their psychiatric/mental health clinical rotation express an array of emotions as they frequently view the setting as foreign. Two assignments, reflective journaling and a form of expression were incorporated into clinical to provide students an opportunity to reflect and convey their thoughts and feelings concerning their clinical experiences. Thematic analysis was used to analyze 10 journals and 10 art forms with a written description. Two content themes emerged: A Change in Perspective and Insight. Exemplars of the students’ perspectives are provided. As evidenced by students’ submissions, reflective journaling and creative expression can be an …

Assessment Of Celecoxib Poly(Lactic-Co-Glycolic) Acid Nanoformulation On Drug Pharmacodynamics And Pharmacokinetics In Rats, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP).

MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma …

Blood, Donors And Dollars: Rethinking Financial Sustainability Of Safe Blood Services In Tanzania, Kahabi Isangula, Sharon Brownie, Abela Mahimbo, Solomon Kibona, Abdu Juma, Deus Mogela

School of Nursing & Midwifery, East Africa

Introduction: Collection, processing and distribution of safe blood in Tanzania occurs within a free-for-service context, that is, a collection from non-remunerated blood donors and distributing freely to the needy people through health facilities. The safe blood services in the country appear to be crippled with many challenges and cannot meet the demand for blood and its products. As such, a need for rethinking collection methods, financial models and possible mechanisms for donor remuneration is evident.

Methods: In this paper, we venture on multi-stakeholder meetings and ongoing discussions regarding the internal mechanisms of safe blood transfusion financing. The intent is to …

Vitamin D Levels In Black African Adults At The Aga Khan University Hospital Nairobi, Elizabeth Muringa Kagotho

Master of Medicine in Clinical Pathology

Introduction: Vitamin D has been known for centuries for its benefits in bone health. Recent observational studies have however demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few and have shown that vitamin D deficiency ranges from 5-91%. In view of the difference in skin colour, …

Getting Back To Our Roots, Emily J. Jacobs

Williams Honors College, Honors Research Projects

Completing this senior honors project afforded the opportunity to develop activities around the topics of basic gardening skills, cooking skills, and the importance of quality nutrition for the students from the Center for Child Development Day Camp. Seven lesson plans were developed in collaboration with Mrs. Kathy Schupp, the director of the Nutrition Center. At the beginning of summer, discussion took place regarding the types of nutrition information that could be learned from working in the Schrank Hall South teaching garden. The Great Garden Detective Adventure was used as a resource in planning lessons for the students. This book was …

Differences In Rhodococcus Equi Infections Based On Immune Status And Antibiotic Susceptibility Of Clinical Isolates In A Case Series Of 12 Patients And Cases In The Literature, Praveen Gundelly, Yasuhiro Suzuki, Julie A. Ribes, Alice C. Thornton

Internal Medicine Faculty Publications

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P > 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P > 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. …

The Role Of Renal Replacement Therapy In The Management Of Pharmacologic Poisonings, Aibek E. Mirrakhimov, Aram Barbaryan, Adam Gray, Taha Ayach

Internal Medicine Faculty Publications

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These …

Reforming American Medical Education In The Past, Present And Future, Alexey Abramov

Quill & Scope

No abstract provided.