UNTHSC Scholarly Repository

PERCEPTIONS AND EXPERIENCES OF HISPANIC WOMEN IN A COMMUNITY-BASED CANCER SUPPORT GROUP

Criselda Hinojosa et al.

PERCEPTIONS AND EXPERIENCES OF HISPANIC WOMEN IN A COMMUNITY-BASED CANCER SUPPORT GROUP Criselda Hinojosa*, Betty Tonui**, Marcela Gutierrez** *Cancer Care Services, 623 South Henderson Street, Fort Worth, Texas, 76104, ** School of Social Work, University of Texas at Arlington, 211 South Cooper Street, Arlington, TX 76019 Background: Compared to White women in the United States, Hispanic/Latina women are more likely to be diagnosed with cervical cancer. This holds true in Tarrant County, Texas, where Hispanic/Latina women not only have higher rates of cervical cancer than Whites or Blacks, but are also more likely to have a late-stage diagnosis of cervical cancer. Within Tarrant County, they are also at least 40% more likely to die from cervical cancer than Whites or Blacks. Research suggests that these health disparities in cancer screening and cancer outcomes are primarily due to unequal access to health care resulting from barriers in the health care system, cultural competence of health care providers, and cultural and economic barriers. Evidence of this exists within Tarrant County, where Hispanic/Latina women have the lowest rates of cervical, breast, prostate and colorectal cancer screening of all groups. Community-based cancer care organizations often seek to address these disparities in cancer screening and outcomes through services such as cancer navigation, advocacy and economic assistance. However, it is unknown how local immigration policy might affect the effectiveness of the services. This exploratory study seeks to understand the perceptions and experiences of a group of Hispanic/Latina women participating in a community-based cancer support group within Tarrant County, the only metropolitan county in Texas to exclude low-income undocumented immigrants from county-funded clinic and preventive care. Methods: This study utilized a community-based participatory research (CBPR) approach to develop, implement and analyze a focus group with seven Hispanic/Latina women participating in a community-based support group. Participants were recruited from a support group provided by a community-based nonprofit organization that provides cancer care services without government funding, and is thus able to provide services to all individuals regardless of immigration status. Participants had to be 18 years and older, have a previous diagnosis of any cancer type, reside in Tarrant County, and not be in active treatment. The focus group was co-facilitated in Spanish by an academic researcher and a social worker at the nonprofit organization that facilitates the support group and subsequently transcribed and translated by a student researcher. The focus group was then reviewed by a staff member, board member, student researcher and principal investigator to identify significant statements and possible themes. The primary investigator reviewed these statements and proposed four primary themes agreed upon by all individuals. Results: The four themes that emerged from the study were immigration status and language as barriers to health care, the role of family, social and emotional support, and survivorship services. Findings suggest that immigration status and limited English fluency are significant barriers for Hispanic/Latina women in accessing health care services. The role of family emerged not only as a source of support, but also as an unmet need in caregiver services. Social and emotional support were important priorities for participants, many of whom talked related these as primary benefits of participating in the support group whether they had were in long-term remission or in active treatment. A secondary benefit of the support group, survivorship services, also emerged as many women talked about what it meant to be a survivor and how they benefitted from continued guidance to access resources. Conclusion: This focus group sought to capture the perspectives and experiences of a single group of Hispanic/Latina women participating in a community-based cancer support group in the only metropolitan county in Texas to exclude low-income undocumented immigrants from county-funded clinic and preventive care. The results of this study help to illustrate possible dynamics that contribute to cancer disparities among Hispanic/Latina women in Tarrant County and across the nation. Future research should seek to survey women across the state to identify whether a relationship exists between local immigration policies, immigration status, and cancer screening, diagnosis and mortality. Cancer care providers might also utilize this information in assessing the needs of their service population in order to identify barriers such as immigration status and English language fluency, develop and evaluate social and emotional support services, and engage Hispanic/Latina women in survivorship services.

Colorectal Cancer Knowledge and Screening Habits among Refugee Populations in DFW

Victoria J. Kwentua et al.

COLORECTAL CANCER KNOWLEDGE AND SCREENING HABITS AMONG REFUGEE POPULATIONS IN DFW Victoria Kwentua*, Amy Raines-Milenkov, DrPH**, Eva Baker, MPH**, Emelda Thein**, Radhika Subedi**, Iram Qureshi* *School of Public Health, **Department of Obstetrics and Gynecology, UNT Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, Texas 76107 Colorectal cancer (CRC) is the fourth most common cancer worldwide. Although resources are available to screen for and to treat CRC, refugees living in the United States report low levels of screening. Over the past several years, Texas has resettled the largest numbers of refugees, yet little research has investigated the need for colorectal cancer screening in refugee populations. This study aimed to assess local refugees’ current knowledge of and experience with colon/rectal cancer and screening. This information is needed to guide effective CRC education and screening efforts among this underserved population. Refugees, previously enrolled in a community-based refugee health program, the Building Bridges Initiative (BBI), were contacted by bilingual lay health educators to complete a 23-question phone interview on their familiarity with CRC. The survey was translated into Nepali and Karen by a professional translator, and included detailed descriptions of colon cancer and available screening methods. Descriptive statistics were compiled using statistical analysis software. Twenty-nine of the 43 eligible participants (ages 50-75) agreed to participate. 72% of participants were unaware of colon cancer, and 97% wanted more education on the subject. Familiarity with the screening process and physician recommendation were strong motivators to complete a CRC screening. Local refugee populations are receptive to CRC screening. Programs such as BBI have the structure in place to provide culturally and linguistically appropriate education and tailored evidence-based interventions, which are necessary to reduce health disparities when it comes to CRC screening. Keywords: colon cancer, screening, education

DETERMINATION OF NEW BIOSYNTHETIC PATHWAYS OF ASCORBIC ACID USING BIOINFORMATICS MODELLING

Grant W. Wangila et al.

Literature results shows that plants that have been treated with ascorbic acid (vitamin C) exhibit healthy growth and are resistance to insects resulting to better yield. Plants produce ascorbic acid as they grow, it’s imperative for us to examine in details how this process occurs metabolically. In this project, computer models were used to identify biosynthesis of ascorbic acid in plants, tested for its presence in plant material and suggest ways of how it can be enhanced in plants so that better plants can thrive. Detailed investigation of metabolic pathways of ascorbic acid, degradation in both plants and animals are vital tools that will assist in establishing the threshold concentrations needed. The overall goal of this project is to characterize the biosynthetic and metabolic pathways of ascorbic acid that exist in nature. Bioinformatics algorithms were employed as a tool in finding or engineering new biosynthetic pathways of ascorbic acid and suggested ways of introducing these new pathways into plants that do not currently synthesize vitamin C.

Obstacles Associated with Physician Referral of Patients into Clinical Trials

Nick Torrez — Fri, 12 May 2017 09:31:06 PDT

Understanding the safety and efficacy of potential new medications relies on evidence gained through the participation of subjects in clinical drug trials. Many clinical trial sites struggle with recruitment of suitable participants which can delay the progress of drug development. Physicians can play a significant role in influencing patients to enter into a clinical trial, however many physicians due not utilize their unique position to facilitate the recruitment of patients into clinical trials, which may help to advance medical science and improve future treatment options. The lack of participation by physicians in the referral of patients into clinical trials (Crosson et al. 2001; Daugherty C, 1995; Jenkins and Fallowfield, 2000; Lara et al., 2001) can potentially be explained by various obstacles. We propose that these obstacles may be issues such as time, lack of knowledge about clinical trials, lack of clinical trials suitable for patients, language barriers, conflict of interest, communication with local investigators, and trust in medical researchers.

Adaptation of the Genetic Risk Prediction Model BRCAPRO for Primary Care Settings

Philamer M. Atienza — Fri, 12 May 2017 09:31:02 PDT

Identifying women at high risks of carrying the breast cancer susceptibility genes is crucial for providing timely surveillance and necessary health management interventions. BRCAPRO is one of the most widely used statistical models for breast cancer risk prediction in genetic counseling. It provides carrier probabilities of BRCA1/2 mutations and calculates the risks of developing breast and ovarian cancers. This calculation requires extensive personal and family history information, which makes it difficult to use in primary care where a wider population could be reached. Thus, we developed a two-stage approach for the genetic risk prediction of BRCA1/2 mutation. In the first stage, limited information on the counselee and her family history of cancer are used in simplified versions of BRCAPRO. If the risk at this stage is found to be high, the full BRCAPRO model utilizing the complete family history is implemented in the second stage. We aimed to balance the tradeoff between the amount of information used and the accuracy of the predictions. We explored several first stage tools. BRCAPROLYTE uses information on the affected relatives up to the second degree only. BRCAPROLYTE-Plus additionally includes unaffected relatives by imputing their ages. BRCAPROLYTE-Simple eliminates the need to collect information on the numbers and types of unaffected relatives and imputes them and their ages instead. The study cohorts include 1,917 families mostly at high risk from the Cancer Genetics Network, 796 high-risk families from MD Anderson Cancer Center, and 1,344 population-based families from Newton-Wellesley Hospital. To evaluate the models, we used sensitivity, specificity, area under the curve, and observed versus expected number of carriers. We also considered clinical criteria of number of referrals made by each model. We found the proposed two-stage approach (with BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple at the first stage) has very limited loss of discrimination and comparable calibration with BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. Thus, our two-stage approach allows for practical large-scale genetic risk assessment in primary care.

Assisting the Implementation of a Centralized IRB in Multiple Categories of Research at Medical City of Fort Worth

Pawanpreet Randhawa — Fri, 12 May 2017 09:30:59 PDT

Introduction: As a collection of ethical principles and guidelines regarding biomedical research on humans, the Common Rule has remained largely unchanged since its inception while the clinical research landscape has grown dramatically in size and complexity. Now with the Common Rule being modernized, one of the proposed changes being executed is the requirement of a centralized Institutional Review Board (IRB) for multi-site research studies. This transition of a research site operating under a local IRB to a centralized IRB is expected to greatly improve collaborative studies.

Objective: The main goal of this practicum project is to assist in the implementation of a centralized IRB for multi-site research at Medical City of Fort Worth in order to comply with the changes to the Common Rule.

Methods/Results: To achieve the goal of this practicum project, the operational rules and regulatory processes at Medical City of Fort Worth were updated. This included revising the institutional IRB and FWA, adverse event and serious adverse event reporting, and audit policies, establishing a local database for active studies, converting study-related materials to an e-records system, and revising the institutional exemption status policy.

Conclusion: These activities led to the completion of the transition of Medical City of Fort Worth from a local IRB to a centralized IRB. Additionally, documentation of the process yielded a procedural guide for other institutions undergoing the same transition.

Approaches to mitochondrial genome sequencing using the oxford nanopore minion device

Kelcie C. Thorson — Fri, 12 May 2017 09:30:54 PDT

Current DNA sequencing methods rely on polymerase chain reaction (PCR) to create sufficient copies of targeted DNA fragments to serve as a library. PCR and subsequent clean-up steps add considerable time and cost to the process and provide opportunity for introduction of amplification errors or contamination. The aim of this study was to develop a reliable method for mitochondrial genome sequencing sans PCR using the Oxford Nanopore MinION. Our hypothesis was that results generated from native DNA sequencing would be concordant to sequencing results generated from PCR-enriched libraries. Error-rates of 1.47% (enriched) and 1.26% (native) were observed when sequencing the control DNA. Consensus sequences generated from native and PCR-enriched libraries show an average of 98.7% identity between the two methods.

Measurement of Traumatic Brain Injury (TBI) Inpatient Activity Levels Through Accelerometry

Jeffrey T. Ramsey — Fri, 12 May 2017 09:30:51 PDT

Purpose: The purpose of this study was to use retrospective analysis of actigraphy data to describe activity levels for patients undergoing inpatient rehabilitation. This study also examined the differences between activity levels of the different areas of therapy. The final aim of this study was to examine the affect of demographic factors, and injury characteristics on activity levels.

Method: Fifty individuals with Traumatic Brain Injury (TBI) undergoing inpatient rehabilitation wore accelerometers. Activity Counts (ACs) were summarized in one-minute intervals. ACs, demographic and outcome variables were analyzed using descriptive statistics and general linear regression analysis.

Results: During active therapy patients averaged 241.3 +/- 97.8 AC, which decreased to 142.2 +/- 74.1 during non-active therapy. Recreational time had an average of 112.8 +/- 59.5 AC, and sleep time had an average of 26.7 +/- 14.8 AC. Using predetermined definitions of physical activity, patients were determined to be inactive during therapy and sedentary/inactive for large portions of their stay. Linear regression analysis showed that the main factor with a negative association with physical activity is age.

Discussion: The findings of this study demonstrate that patients undergoing inpatient rehabilitation are largely inactive or sedentary. Although age was determined to have the largest impact on physical activity, the other demographic and outcome measures analyzed by this study along with other confounders’ impact on physical activity require further study to determine the best way to safely increase patient activity.

Creating novel purification and biochemical characterization protocols for C. collagenase from Clostridium histolyticum, developing a new emergency medicine product, and formulating several novel therapies for chronic and acute wound treatment

Jason P. Mars — Fri, 12 May 2017 09:30:48 PDT

The pharmaceutical industry not only includes infinite areas of specialization, but also consists of distinct areas that do not typically overlap. Biotechnology is the branch of medicinal research that bridges the gap between the fields within the pharmaceutical industry by being able to take on the challenges that require knowledge of a vast range of information. This practicum was organized to put the scientific knowledge and the interdisciplinary practices of biotechnology to use in a modern day, pharmaceutical company specializing in wound therapy and skincare: Smith & Nephew Biotherapeutics. Wound therapy has the widest range of application due to being one of the few fields that affects everyone, regardless of medical disposition. The specific goals of this practicum were: to develop novel purification and biochemical characterization protocols for C. collagenase from Clostridium histolyticum to replace current production methods of Santyl®, to develop a working prototype of a venom-based, hemostatic film, and perform reformulation, quality control, troubleshooting, and verification testing on samples of Regranex®, Iodosorb “Max”, and EU-Collagenase. Every goal presented was approached with the end results of saving Smith & Nephew costs, reducing bioburden of production, and creating more efficient protocols to bring Smith & Nephew into the modern age.

Mechanisms of Sympathoexcitation via Hyper-Acute Intermittent Hypoxia in Humans: Implications for Obstructive Sleep Apnea

Noah P. Jouett — Fri, 12 May 2017 09:30:44 PDT

Obstructive Sleep Apnea (OSA) is a very prevalent disease that predisposes affected individuals to develop cardiovascular disease, mostly through secondary hypertension, which is independent from co-morbid conditions. Animal and human investigations over the past 25 years have demonstrated that intermittent hypoxia (IH) produces elevations in arterial pressure consistent with what is observed in OSA patients. The generation of this hypertension is dependent on an intact peripheral chemoreflex and an intact sympathetic nervous system. However, the mechanistic link between IH and elevated sympathetic nerve activity (SNA) is not well known. Animal investigations have demonstrated that adaptations in the carotid body, in the central nervous system structures that participate in the chemoreflex arc, and in the adrenal medulla are mechanistically related to the development of hypertension in rodents exposed to chronic IH. These studies have also identified the critical role of reactive oxygen species (ROS) and activation of angiotensin II type 1a receptors (ATR1a) in these maladaptations. Hence, antioxidants and angiotensin receptor blockers (ARBs) may have important treatment potential in OSA patients with hypertension. Both of the projects described in this dissertation will provide the beginning steps of translating animal studies of chronic IH that have uncovered the role of these particular molecular mediators to human patients.

The first project investigates the sympathoexcitatory role of ROS in short-term IH (20 minutes) in humans. Previous investigations in rodents have demonstrated that ROS are generated in the carotid body and in nuclei that participate in the chemoreflex neural arc in response to chronic IH.

Importantly, these studies demonstrate that oral ingestion of antioxidants reduce the production of sympathetically-derived catecholamines from the adrenal medulla, and attenuate the increased acute and sustained carotid body firing in response to chronic IH. Moreover, in animal studies injection of antioxidant substances directly into the cerebral ventricles reduces centrally derived sympathetic outflow. In the present study, young, healthy human subjects ingested either vehicle placebo or the lipid-soluble antioxidant N-acetylcysteine (N-AC), and were then exposed to very short term IH (20 minutes), while direct measurements of SNA via muscle SNA (MSNA) and beat-to-beat arterial pressure were collected in tandem with venous blood samples via intravenous catheter, which was assayed for superoxide with electron paramagnetic spectroscopy (EPR). This experimental design tested the hypothesis that N-AC reduces the MSNA and arterial pressure responses to 20 minutes of IH and reduces the measurements of peripheral venous superoxide. N-AC reduced the sympathetic and arterial pressure response to our paradigm of IH in healthy humans. However, measurements of peripheral superoxide via EPR did not demonstrate any effects of acute IH or N-AC. This indicates that N-AC may be exerting a primarily central effect in the reduction of very short IH-mediated sympathoexcitation, versus modulating peripheral chemoreceptor afferent transmission.

The second project investigated the role of ATR1a activation in our paradigm of acute IH and the subsequent sympathoexcitation in human subjects. Indeed, animal studies have demonstrated that activation of ATR1a mediate, in part, the elevated lumbar SNA (LSNA) in rodents exposed to chronic IH. Furthermore, similar animal studies have identified the role of angiotensin II in mediating the sustained elevation of carotid body discharge after chronic IH. In humans, studies have demonstrated that ingestion of Losartan reduces the arterial pressure response to a single 6 hour exposure of IH. However, it is not clear how Losartan affects the MSNA response to acute IH in humans. Hence, in the second study of this dissertation, human subjects were exposed to acute IH after ingesting Losartan or cellulose placebo while MSNA and arterial pressure were assessed. Furthermore, these measurements were continued into the post-IH recovery period. This experimental design tested the hypothesis that Losartan reduces the immediate and sustained sympathoexcitatory and arterial pressure responses to IH. This results of this study demonstrated that Losartan significantly abrograted the MSNA response to IH and virtually abolished the arterial pressure response, both acutely and during the recovery period. This indicates that activation of ATR1a play an important and substantial role in the sympathetic activation observed after a short-bout of IH in human subjects.

In summary, these studies demonstrate that human IH-mediated sympathoexcitation and hypertension involves generation of oxidative stress (independent of peripheral superoxide) and activation of ATR1a.

“Ecstasy” to Addiction: Mechanistic and Reinforcing Effects of Synthetic Cathinone Analogs of MDMA

Sean B. Dolan — Fri, 12 May 2017 09:30:40 PDT

Following widespread scheduling, many synthetic cathinone compounds have been diverted from “bath salts” to “Ecstasy” tablets or “Molly” powder formulations in addition to or in lieu of 3,4-methylenedioxymethamphetamine (MDMA). The current study aimed to assess the mechanism and reinforcing effects of three under-researched synthetic cathinone analogs of MDMA frequently used as adulterants in “Ecstasy” formulations: methylone, butylone, and pentylone. To assess the mechanism of these compounds in vitro, we utilized whole-cell patch clamp electrophysiology on HEK293 cells expressing the serotonin transporter (SERT). The abuse-related, in vivo mechanisms were determined using a drug discrimination assay with rats trained to discriminate methamphetamine, the hallucinogenic phenethylamine 2,5-dimethoxy-4-methylamphetamine (DOM), or MDMA from vehicle, and drugs that substituted were tested with the D1-like receptor antagonist SCH23390 to assess relative differences in dopaminergic signaling. The reinforcing effects were assessed in an intravenous self-administration assay using continuous and progressive ratio schedules of reinforcement. Methylone and butylone, like MDMA, produced inward currents at SERT, indicative of a substrate-like mechanism. Each test compound fully substituted for the discriminative stimulus effects of methamphetamine. MDMA, methylone, and butylone substituted partially for DOM, and methylone and butylone substituted fully for MDMA. Pentylone, conversely, substituted partially for MDMA, but failed to substitute for DOM. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding, with pentylone being least sensitive to these antagonistic effects, but failed to attenuate MDMA-like responding against MDMA, methylone, and butylone. Each test compound maintained robust self-administration under a continuous schedule of reinforcement, but pentylone was the most reinforcing test compound under a progressive ratio. These data indicate that methylone and butylone produce complex discriminative stimulus effects, similar to MDMA, that are mediated by both dopamine and serotonin, whereas pentylone is predominately dopaminergic. The underlying differences in relative dopaminergic and serotonergic mechanisms likely influence the relative abuse liability, with pentylone’s predominately dopaminergic mechanism conferring a greater reinforcing efficacy relative to the more serotonergic methylone and butylone. In conclusion, incorporation of these compounds into “Ecstasy” formulations, especially pentylone, may lead to compulsive, uncontrolled use of “Ecstasy”.

Identifying Risk Factors for 30-Day Readmissions in Patients with Cirrhosis

Stephen L. Tan — Mon, 08 May 2017 08:52:00 PDT

Hospital readmissions have been a main focus of hospitals around the US since 2012. Hospitals with higher than excepted readmission rates are penalized financially and named publically on the CMS website. Cirrhosis is a disease with high readmission rates due to the many complications associated with the disease. The aim of the study is to identify factors that may predict 30-day readmission in patients with cirrhosis.

A total to 262 patients admitted to Baylor Scott and White All Saints Medical Center between September 2013 and September 2015 were included in this study. Patients were initially identified by the following initial diagnoses and ICD-9 codes: alcoholic cirrhosis, cirrhosis not due to alcohol, biliary cirrhosis, hepatic encephalopathy, ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, esophageal varices with bleeding, portal hypertension, or paracentesis. The patients’ height, weight, serum sodium, serum albumin, serum bilirubin, serum creatinine, INR, the number of medications prescribed to the patient at discharge, and whether or not the patient was readmitted within 30 days.

The 30-day readmission rate for this population was 32.4%. A binary logistic regression was performed to find significant predictors of an early readmission. The MELD score and the number of medications prescribed at discharge were significant variables in predicting readmissions for this population. These findings can lead to implementation of new strategies that aim to reduce early readmissions in the cirrhotic population at Baylor Scott and White All Saints Medical Center.

A Cadaveric Investigation of the Dorsal Scapular Nerve

Vuvi H. Nguyen — Mon, 08 May 2017 08:51:57 PDT

Dorsal scapular nerve (DSN) syndrome is often associated with sharp, dull, or aching pain in the upper extremity and back. The primary cause of pain is the entrapment of this nerve at the middle scalene muscle. Even though there is clinical evidence that DSN syndrome exists, it is often overlooked during clinical diagnosis. The purpose of this study is to locate the surface projection of the DSN relative to the middle scalene muscle while using the laryngeal prominence as a reference point. From 20 embalmed adult cadavers, 23 DSN were dissected and documented regarding its spinal root origins, anatomical route, and muscular innervations. A transverse plane through the laryngeal prominence was established to measure the distance of the DSN as it enters, crosses, and exits the middle scalene muscle. Approximately 70% of the DSNs originated from C5, 22% branched from C4, and 8% from C6. In regards to the route of the DSN in relation to the middle scalene muscle, 74% of the DSNs pierced this muscle, 13% crossed this muscle anteriorly, and 13% traveled posterior to this muscle. About 48% of the DSNs supplied the levator scapulae muscle only and 52% innervated the levator scapulae and both the rhomboid muscles. The average distances from a transverse plane of the laryngeal prominence to where the DSN entered, crossed, and exited the middle scalene muscle were 1.50 cm (±0.88 cm), 1.79cm (±0.89 cm), and 2.08 cm (±0.96 cm) respectively. Injection studies were performed on 10 un-dissected embalmed cadavers to verify the accuracy of our surface projection measurements of the DSN relative to the middle scalene muscle. These injections were performed at approximately 2.08 cm (~1 thumb interphalangeal joint width) from the transverse plane of the laryngeal prominence. Dissections at these injection sites revealed that the scalene muscles were consistently located. The middle scalene muscle was accurately located in approximately 50% of the injections. The goal of this research is to understand the variability in DSN's anatomy as well as introduce a method that will assist clinicians to efficiently pinpoint and therefore treat patients with DSN entrapment.

MaCHTools: Additional functionality for the imputation software MaCH

Jeffrey S. Mitchel Jr. — Mon, 08 May 2017 08:51:53 PDT

Imputation of unknown genotypes is becoming a standard procedure in exploratory genetic association studies. Imputation is accomplished by comparing observed data from the study population to reference panels of individuals who are from a genetically similar population and genotyped at a dense set of polymorphic sites. Linkage disequilibrium within the reference panels is used to construct haplotypes and extrapolate allelic correlations in the test sample. Imputation has been shown to be accurate for the inference of genotypes at unobserved SNPs, as well as for quality control measures at genotyped locations. Imputing genotypes also allows cohorts that were genotyped on different platforms to be combined in a joint or meta-analysis. One of the most widely used imputation software packages is MaCH (http://csg.sph.umich.edu//abecasis/mach/). MaCH uses a powerful and accurate Markov chain-based algorithm, however its usability is lacking. MaCHTools allows the user to streamline their workflow with MaCH through input file specification, error checking, and QC measures,

MaCHTools began as a series of Java scripts used to check input files and QC raw data as an initial step before imputing additional genotypes in MaCH. This set of scripts became invaluable to the GWAS workflow, but they were unpolished and ill-suited for public release to benefit the scientific community. This project aimed to bundle the scripts into a single executable program that provides a graphical user interface (GUI) to facilitate use by students and researchers to aid in streamlining the GWAS workflow. Additional functionalities include more efficient launching of jobs to compute clusters and compatibility with different Linux job handlers, the ability to easily switch between different GWAS projects including switching between different genotype data and reference datasets, more simplistic specification of parameters and thresholds, and several other usability improvements.

The GWAS workflow that includes dataset preparation with MaCHTools coupled with haplotype estimation and imputation with MaCH was validated by replicating results from a published study of the genetic basis of Alzheimer’s endophenotypes in the Texas Alzheimer’s Research and Care Consortium. A similar analysis was then performed to determine the genetic basis of D, a latent variable that represents the dementing process.

Inorganic nanoparticles for applications in biomedical sciences

Bhuvaneswari Koneru — Mon, 08 May 2017 08:51:50 PDT

Nanomedicine is one of the fastest emerging fields in recent times. Small size, tunable surface properties and efficient drug loading capacity are some of the properties that make them a promising option for various applications in biological sciences. Using nanocarriers for drug delivery offers several advantages like delivery of poorly soluble drugs, better bioavailability, targeted delivery and extended release of drugs. In this work, we demonstrated the formulation and methods of use for three different nanocarriers.

1) ¹⁶⁶Ho iron garnet nanoparticle-containing bandages for treatment of squamous cell carcinoma of skin: Squamous cell carcinoma (SCC) of skin is a type of non-melanoma skin cancer (NMSC) which constitutes 20% of all NMSCs. While surgery is the primary treatment option for SCC, radiation therapy also plays an irreplaceable role in the treatment of SCC. Our lab has previously reported an electrospun nanofibrous polyacrylonitrile (PAN) bandage containing holmium-165 iron garnet (¹⁶⁵HoIG) nanoparticles, which can be neutron activated to ¹⁶⁶Ho and used for radiotherapy of SCC. The synthesis, characterization and stability of the bandage were also reported. Here, we tested the in vivo efficacy of the 166HoIG-PAN bandage for the treatment of SCC. When treated with the radioactive bandage, tumor progression was significantly low in mice compared to those with non-radioactive bandage. The dose used was clinically relevant. Histological evaluation showed no damage to surrounding organelles.

2) Targeted chemotherapy for non-small cell lung cancer using antibody-coated gold nanoparticles: Non-small cell lung cancer (NSCLC) is a type of lung cancer which constitutes nearly 80% of all lung cancers. Being detected at later stages limits its treatment, thus resulting in a lower fiver year survival rates. Though limited by their dose related side effects, platinum drugs are the first line of treatment for NSCLC. Several Pt(IV) complexes, which are the prodrugs of Pt(II) compounds are shown to have potent anti-cancer activity and are capable of overcoming the limitations of Pt(II) compounds. Not many targeted therapies are available for NSCLC because of its complex molecular pathology. CD22 is an adhesion molecule that is shown to be broadly expressed on NSCLC cell lines. Hence, in this project, we developed CD22 targeted gold nanoparticles to deliver Pt(IV) complex for the treatment of NSCLC. Synthesis and characterization of polyethylene glycol (PEG) coated gold nanoparticles conjugated with Pt(IV) complex and an antibody against CD22 is reported. The expression of CD22 on various NSCLC and normal cell lines and the uptake of the synthesized nanoparticles in these cell lines was studied.

3) Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia Coli: Tetracycline (TC) is a very well-known antibiotic whose use has been limited due to drug resistance. Nanoparticle formulations, can help overcome the resistance mechanisms to certain extent. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile Crystalline Material-41 (MCM-41), a type of MSN, that has a mesoporous structure with pores forming channels in a hexagonal fashion. We used MCM-41 mesoporous silica nanoparticles for the delivery of TC and tested its efficacy in E. coli. The TC containing nanoparticles showed a burst release of drug in PBS and in LB broth medium and most of the drug was released within 1 h. The TC loaded MSNs showed enhanced inhibition of E. coli compared to free TC and unloaded MSNs at a concentration of 0.5μg/mL and 1μg/mL. Further, the TC containing MSNs uptake by E. coli was demonstrated using transmission electron microscopy.

The Role of Cerebral Oxygenation and Perfusion on Tolerance to Central Hypovolemia

Victoria L. Kay — Mon, 08 May 2017 08:51:45 PDT

Tolerance to central hypovolemia, including hemorrhage, is highly variable between individuals. The role of cerebral oxygenation and regional cerebral perfusion on tolerance to central hypovolemia has not been explored. Protection of posterior cerebral perfusion may be an important factor in tolerance, as the posterior circulation supplies blood to the autonomic and respiratory control centers in the brain stem. Additionally, despite the reduction in cerebral oxygen delivery with central hypovolemia via decreased flow, the role of compensatory increases in oxygen extraction and subsequent cerebral tissue oxygenation on tolerance have not been identified. The oscillatory pattern of cerebral blood flow has recently been identified as a contributing factor to improving tolerance to central hypovolemia, and may be more important than the protection of absolute flow. This finding was demonstrated when comparing high vs. low tolerant individuals, and in subjects who exhibited increased tolerance to central hypovolemia while breathing against inspiratory resistance. We hypothesized that healthy human subjects with naturally high tolerance to central hypovolemia, and subjects breathing against inspiratory resistance under hypovolemic stress would exhibit 1) protection of cerebral oxygen saturation (ScO₂); 2) prolonged preservation of cerebral blood flow in the posterior versus anterior cerebral circulation, and; 3) higher LF oscillations in cerebral blood flow.

The major findings from these investigations are: 1) subjects with high tolerance to central hypovolemia exhibited protection of ScO₂ and velocity in the posterior cerebral circulation; 2) LF oscillations did not play a role in the protection of ScO₂; 3) resistance breathing improved tolerance to central hypovolemia, but not via protection of ScO₂ or velocity in either the anterior or posterior cerebral circulation, and; 4) resistance breathing was associated with increased high frequency oscillatory power in arterial pressure, anterior and posterior cerebral blood velocity, and ScO₂.

We conclude that individuals with naturally high tolerance to central hypovolemia exhibit protection of cerebral tissue oxygenation and prolonged preservation of perfusion within the posterior cerebral circulation, but not in the anterior circulation, thus delaying the onset of presyncope. Improved tolerance to central hypovolemia via resistance breathing was not related to these mechanisms, but may have been associated with increased depth of breathing, subsequently decreasing intracranial pressure and increasing cerebral perfusion pressure.

Statins and PCSK9 Inhibitors: How They Have Shaped Medicine, A Comparative Review

Phillip R. Escarsega — Mon, 08 May 2017 08:51:41 PDT

Keeping serum low density lipoprotein cholesterol (LDL-C) levels within recommended ranges has been proven to lower the risk of cardiovascular events from occurring. To lower LDL-C levels, statins have been the drug of choice for the last few decades since they were introduced. However, the discovery of PCSK9 inhibitors and new knowledge about how they are able to lower LDL-C levels may provide physicians a new path to consider when choosing a course of treatment in patients that fit the criteria for PCSK9 inhibition. Furthermore, there are several risks with statins which may turn physicians towards using PCSK9 inhibitors in patients with uncontrolled LDL-C. This practicum report is a review of the latest developments in PCSK9 drugs and how they compare to statins in lowering LDL levels.

Study of Kinematics and Gait in Dynamic Response Feet across Functional K-Level Categories.

Russell J. Donevant — Mon, 08 May 2017 08:51:37 PDT

In the United States, the Medicare Functional Classification Level (MFCL or K-level) classification system exists in order to estimate a patient’s rehabilitation potential. Physicians assign a K-level rating from 0-4 of increasing functionality, which serves to designate what kind of prosthetic device to provide a patient with and what insurance will cover. This study aims to interpret kinematic data recorded from transtibial amputees with two different functional levels of prosthetic feet and interpret the effect on gait and functional performance when switching to a higher/lower prosthetic level than the one currently equipped with. Kinematic data are collected via motion-capture and force-plate technologies while subjects interact with a virtual reality environment and processed using the GOAT (Gait Offline Analysis Tool) analysis software.

Implementation of an Updated Standard Operating Procedure For Investigational Product Management

Johnny V. Dang — Mon, 08 May 2017 08:51:34 PDT

To ensure the highest validity of clinical trials, the safety and efficacy of the investigational products that are used in the studies must be of highest priority. This task is accomplished through the use of a research site’s standard operating procedure.

This practicum study addressed the standard operating procedure for the handling of investigational products at The Center for Cancer and Blood Disorders. A survey was used to assess the knowledge and perception about the standard operating procedure from those that are involved in the handling of investigational products. Information from this survey was used to adjust and make changes to the existing standard operating procedure to better ensure the safety and efficacy of the investigational products that are being studied at the site.

Submission to the IRB: Will Modified Training Improve the Probability of Successful Submission of IRB Protocols?

Yuhung H. Chou — Mon, 08 May 2017 08:51:30 PDT

The ability to design, conduct, and oversee of a research project has becoming essential for the pharmacy residents to become pharmacists. Each year, pharmacy students undergo training on the specialized institutional review board (IRB) program at Baylor Scott and White Research (BSWRI) and how to submit their research application to the IRB. It is crucial for the pharmacy residents to undergo the IRB training since they typically struggle to submit their research applications due to lack of research background during undergraduate years. This year’s training was modified to test whether the change will improve the submission process compared to the training in 2014 by implementing memory aids such as skeleton outlines and emphasis on important materials by the presenter. The effectiveness of the training was measured by the average number of times that the residents submitted to the IRB, as tallied by the iRIS database. The residents in 2016 performed the same compared to the residents in 2014. Further investigation needed to improve submission numbers.