Digital Commons Network^™

The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam

USF Tampa Graduate Theses and Dissertations

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. CRC is a life-threatening disease due to therapy-resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC are still a significant challenge. Moreover, the treatment of metastatic CRC considered palliative for many years aimed for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Hence, investigating new molecular mechanism(s) that lead to colorectal carcinogenesis may give insight into the therapeutic target. …

Multimodal Treatment And Neoadjuvant Chemotherapy Trends, Utilization And Survival Effects In Intrahepatic Cholangiocarcinoma – A Propensity Score Analysis, Ovie Utuama

USF Tampa Graduate Theses and Dissertations

Intrahepatic Cholangiocarcinomas (ICC) are fatal malignancies common among the elderly. Patients are diagnosed late and often relapse, even after curative-intent surgery (CIS). In this context, additional systemic chemotherapy (multimodal treatment) is recommended for most patients but reported survival benefits are minimal and are limited to small single institutional studies. For this reason, using a national cancer registry, we sought to characterize multimodal treatment trends and utilization in general and neoadjuvant chemotherapy, specifically, as well as evaluate their survival effects among the larger population. We hypothesized that, 1). Elderly ICC patients would have survival benefits equivalent to younger patients, 2). Neoadjuvant …

Understanding The Influence Of The Cancer Microenvironment On Metabolism And Metastasis, Shonagh Russell

USF Tampa Graduate Theses and Dissertations

Cancer is a complex and heterogeneous disease. Not only is there considerable variability between different cancer types, but there is enormous variability between and within patients who have the same type of cancer. Within tumors, there are multiple cell types, including cancer cells, stromal cells, and immune cells. The tumor microenvironment often induces the healthy cells to become pro-tumorigenic. Cell metabolism is exquisitely sensitive to changes in the tumor microenvironment and can be measured to infer the aggressiveness of cancer and predict response to therapy. In this dissertation, we aim to understand how the microenvironment, specifically low pH, affects the …

Widow Narratives On Film And In Memoirs: Exploring Formula Stories Of Grief And Loss Of Older Women After The Death Of A Spouse, Jennifer R. Bender

USF Tampa Graduate Theses and Dissertations

This dissertation analyzes narratives (written and mediated) about widows’ post-loss experiences—specifically the ways in which these women embody and adjust/adhere to their post-loss widow identities—and whether or not the canonical/formula stories about widows reflect current experiences of widowhood. I look at older widowed women—both those in well-read widow memoirs and also in media portrayals of widows on film. The canonical view of widows as not attractive, not useful, and not interesting needs to be reexamined in light of changing ideas about gender roles and increased longevity. Surely older women have experiences, desires, and goals that encompass more than being socially …

The Left Behind Generation: Instructional Practices To Increase The Technological Literacy Of Older Adults, Daphne Pace Phillips

USF Tampa Graduate Theses and Dissertations

This study sought to explore the utilization and perception of best practices by community-based technology training programs when instructing older adults to become technologically literate. The target population included adults age 55 years and older of the Baby Boomer generational cohort who ranged academically from possessing a high school diploma or General Education Diploma (GED) through a college degree and had enrolled in a local technology training program to improve their technological skill level with the goal of obtaining employment and/or to remain functionally independent. This study was conducted at three community technology training centers located in the southeast that …

Supporting Persons With Dementia In Communicating Their Care Preferences, Vanessa L. Burshnic

USF Tampa Graduate Theses and Dissertations

Person-centered care is important to the quality of life of nursing home residents with dementia. Preference assessments enable person-centered care by documenting residents’ preferred activities. Residents with severe dementia are less likely to have a role in preference assessment due to communication challenges associated with the disease. External supports (visual and text cues) are effective in improving the communication of residents with dementia, but these cues are often not used in practice. Standard assessment (verbal questioning) places greater demands on short-term memory and attention, which are known deficits in dementia.

Applying a within-subjects design, this study evaluated two conditions (standard …

Using A Stress Process Model To Examine Longitudinal Racial Differences In Well-Being And Health: Results From A Population-Based Study Of Caregiving, Adrian N. S. Badana

USF Tampa Graduate Theses and Dissertations

As the older adult population of the United States increases over the next decade, many family caregivers will be needed to provide care for aging loved ones. The growing diversity of the population may also mean that more racial/ethnic minority caregivers will be providing care to older family members. Most of the studies examining race and caregiving have focused on racial differences in stress, coping, well-being and health among White and Black family caregivers. However, previous research examining racial differences in caregiving has often been limited to smaller convenience samples of caregivers, which limit generalizability of study findings. In this …

Contribution Of Retrotransposons To Breast Cancer Malignancy, Isaac D. Raplee

USF Tampa Graduate Theses and Dissertations

The components contributing to cancer progression, especially the transition from early to invasive are unknown. Consequently, the biological reasons are unclear as to why some patients diagnosed with atypia and ductal carcinoma in situ (DCIS) never progress into invasive breast cancer. The “one gene at a time” approach does not sufficiently predict progression. To elucidate the early stage progression to invasive ductal cancer, expression signature of transcripts and transposable elements in micropunched samples of formalin-fixed, paraffin embedded (FFPE) tissue was conducted. A bioinformatics pipeline to analyze poor quality, short reads (>36 nts) from RNA-Seq data was created to compare …

Medical Decision Making Among Individuals With A Variant Of Uncertain Significance In A Hereditary Cancer Gene And Those With A Chek2 Pathogenic Variant, Deanna J. Almanza

USF Tampa Graduate Theses and Dissertations

Despite national guidelines, women with a BRCA VUS or CHEK2 pathogenic variant are choosing to have risk-reducing surgeries such as bilateral mastectomies which are not aligned with their level of cancer risk based on genetic test results alone. Semi-structured telephone interviews were conducted with 6 women with a BRCA VUS and 12 with a CHEK2 pathogenic variant exploring the factors influencing their decision-making process when considering medical management options. Patients from a cancer registry agreed to a recorded telephone interview. Coding was performed using the main constructs from the Ottawa Patient Decision Guide including: knowledge, uncertainty, values, and support. Iterative …

Comparing Family Sharing Behaviors In Brca Carriers With Palb2 Carriers, Joy E. Kechik

USF Tampa Graduate Theses and Dissertations

Identifying individuals with hereditary cancer predisposition can improve health outcomes for patients and their family members through early cancer detection and prevention strategies. Prior research about family sharing of genetic test results among those with hereditary breast cancer has overwhelmingly been limited to the BRCA1 and BRCA2 genes. The present study sought to compare family sharing behaviors in women with pathogenic BRCA variants to women with pathogenic variants in the more recently identified and characterized PALB2 gene. A total of 18 BRCA carriers and 13 PALB2 carriers were interviewed about family sharing practices using a semi-structured guide based on the …

Preoperative Mental Health Scores And Achieving Patient Acceptable Symptom State Are Predictive Of Return To Work After Arthroscopic Rotator Cuff Repair, Anirudh K. Gowd, Gregory L. Cvetanovich, Joseph N. Liu, Benedict U. Nwachukwu, Brandon C. Cabarcas, Brian J. Cole, Brian Forsythe, Anthony A. Romeo, Nikhil N. Verma

Orthopaedics and Sports Medicine Faculty Publications

Background: The incidence of rotator cuff repairs has risen dramatically over the past 10 years, most notably in the working-class population. Return to work (RTW) is a valuable outcome measure to set patient expectations before surgery.

Purpose: To establish the rate of RTW after rotator cuff repair with respect to stratified levels of occupational demand (sedentary, light, moderate, and heavy) and to identify clinical factors significantly associated with postoperative RTW.

Study Design: Cohort study; Level of evidence, 3.

Methods: Patients who received rotator cuff repair between 2014 and 2017 were queried from a prospectively maintained institutional registry. Work status was …

Eukaryotic Initiation Factor 3, Subunit C Silencing Inhibits Cell Proliferation And Promotes Apoptosis In Human Ovarian Cancer Cells, Fang Wen, Zhang-Ying Wu, Lei Nie, Qi-Zhu Zhang, Yuan-Kun Qin, Zun-Lun Zhou, Jin-Jian Wu, Xing Zhao, Jun Tan, Darrell Sawmiller, Dan Zi

Psychiatry & Behavioral Neurosciences Faculty Publications

Ovarian cancer remains the leading cause of death among all gynaecological cancers, illustrating the urgent need to understand the molecular mechanisms involved in this disease. Eukaryotic initiation factor 3c (EIF3c) plays an important role in protein translation and cancer cell growth and proliferation, but its role in human ovarian cancer is unclear. Our results showed that EIF3c silencing significantly up-regulated 217 and down-regulated 340 genes. Ingenuity Pathway Analysis (IPA) indicated that the top differentially expressed genes are involved in ‘Classical Pathways’, ‘Diseases and Functions’ and ‘Networks’, especially those involved in signalling and cellular growth and proliferation. In addition, eIF3c silencing …

A Case Report Of Extensive Cerebral Venous Sinus Thrombosis As A Presenting Sign Of Relapsing Nephrotic Syndrome, Janet K. Lee, Kathleen Murray, Swetha Renati

Neurology Faculty Publications

Nephrotic syndrome is defined by three characteristic features including proteinuria of >3 g in 24 hours, hypoalbuminemia of less than 3 g/dL, and peripheral edema. Multiple nephropathies can result in nephrotic syndrome. Most commonly, minimal change disease is seen in children under the age of 10, while adults are more commonly found to have membranous nephropathy. Hypercoagulability and thrombotic sequela can be seen in nephrotic syndrome, regardless of underlying etiology, and thrombosis is most commonly seen in deep veins of the lower extremities and renal veins. Our case identifies an adult with previously diagnosed and treated for minimal change disease …

Safety, Pharmacodynamics, And Potential Benefit Of Omaveloxolone In Friedreich Ataxia, David R. Lynch, Jennifer Farmer, Lauren Hauser, Ian A. Blair, Qing Qing Wang, Clementina Mesaros, Nathaniel Snyder, Sylvia Boesch, Melanie Chin, Martin B. Delatycki, Paola Giunti, Angela Goldsberry, Chad Hoyle, Michael G. Mcbride, Wolfgang Nachbauer, Megan O'Grady, Susan Perlman, S. H. Subramony, George R. Wilmot, Theresa A. Zesiewicz, Colin Meyer

Neurology Faculty Publications

Objective Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435).

Methods Sixty-nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12 weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5–300 mg/day.

Results Omaveloxolone was well tolerated, and adverse …

Central Pain Mimicking Trigeminal Neuralgia As A Result Of Lateral Medullary Ischemic Stroke, Abinayaa Ravichandran, Kareem S. Elsayed, Hussam A. Yacoub

Neurology Faculty Publications

Background. Central pain mimicking trigeminal neuralgia (TN) as a result of lateral medullary infarction or Wallenberg syndrome has been rarely reported. Case Report. We discuss a patient who presented with a lateral medullary infarct and shortly after developed facial pain mimicking TN. We also elaborate on the anatomical pathway of the trigeminal nerve explaining facial pain as a result of a lateral medullary lesion. Discussion. Clinicians should be aware of this typical complication of lateral medullary infarct in order to attain proper management and work-up.

Protocol For Arest: Apixaban For Early Prevention Of Recurrent Embolic Stroke And Hemorrhagic Transformation—A Randomized Controlled Trial Of Early Anticoagulation After Acute Ischemic Stroke In Atrial Fibrillation, David Z. Rose, John N. Meriwether, Michael G. Fradley, Swetha Renati, Ryan C. Martin, Thomas Kasprowicz, Aarti Patel, Maxim Mokin, Ryan Murtagh, Kevin Kip, Andrea C. Bozeman, Tara Mctigue, Nicholas Hilker, Bonnie Kirby, Natasha Wick, Nhi Tran, W. Scott Burgin, Arthur J. Labovitz

Neurology Faculty Publications

Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe.

Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and …

Pathophysiology Of Ganglioside Gm1 In Ischemic Stroke: Ganglioside Gm1: A Critical Review, Wenchao Zhang, Paul R. Krafft, Tianlong Wang, John H. Zhang, Li Li, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be …

Microrna-133a And Myocardial Infarction, Yi Xiao, Jiling Zhao, Julian P. Tuazon, Cesar V. Borlongan, Guolong Yu

Neurosurgery and Brain Repair Faculty Publications

Myocardial infarction (MI) is the leading cause of morbidity and mortality in the world. The infarcted heart displays typical cell death cascades characterized by a loss of cells and fibrotic scarring in the myocardium. Cardiac hypertrophy and fibrosis largely contribute to ventricular wall thickening and stiffening, altogether defining an adverse cardiac remodeling that ultimately leads to impaired cardiac function and subsequent heart failure. Finding a strategy to promote therapeutic, instead of detrimental, cardiac remodeling may pose as a potent MI treatment. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. In particular, microRNA-133a (miR-133a) is …

Prophylactic Treatment Of Hyperbaric Oxygen Treatment Mitigates Inflammatory Response Via Mitochondria Transfer, Trenton Lippert, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.

Gutting The Brain Of Inflammation: A Key Role Of Gut Microbiome In Human Umbilical Cord Blood Plasma Therapy In Parkinson's Disease Model, Jea-Young Lee, Julian P. Tuazon, Jared Ehrhart, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Current therapies for Parkinson's disease (PD), including L-3,4-dihydroxyphenylalanine (L-DOPA), and clinical trials investigating dopaminergic cell transplants, have generated mixed results with the eventual induction of dyskinetic side effects. Although human umbilical cord blood (hUCB) stem/progenitor cells present with no or minimal capacity of differentiation into mature dopaminergic neurons, their transplantation significantly attenuates parkinsonian symptoms likely via bystander effects, specifically stem cell graft-mediated secretion of growth factors, anti-inflammatory cytokines, or synaptic function altogether promoting brain repair. Recognizing this non-cell replacement mechanism, we examined here the effects of intravenously transplanted combination of hUCB-derived plasma into the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rat model of PD. …

Concise Review: Stem Cell Therapy For Stroke Patients: Are We There Yet?, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Four decades of preclinical research demonstrating survival, functional integration, and behavioral effects of transplanted stem cells in experimental stroke models have provided ample scientific basis for initiating limited clinical trials of stem cell therapy in stroke patients. Although safety of the grafted cells has been overwhelmingly documented, efficacy has not been forthcoming. Two recently concluded stroke clinical trials on mesenchymal stem cells (MSCs) highlight the importance of strict adherence to the basic science findings of optimal transplant regimen of cell dose, timing, and route of delivery in enhancing the functional outcomes of cell therapy. Echoing the Stem Cell Therapeutics as …

A Hallmark Clinical Study Of Cord Blood Therapy In Adults With Ischemic Stroke, Paul R. Sanberg, Jared Ehrhart

Neurosurgery and Brain Repair Faculty Publications

The therapeutic application of human umbilical cord blood cells has been an area of great interest for at least the last 25 years. Currently, cord blood cells are approved for reconstitution of the bone marrow following myeloablation in both young and old patients with myeloid malignancies and other blood cancers. Translational studies investigating alternative uses of cord blood have also shown that these cells not only stimulate neurogenesis in the aged brain but are also potentially therapeutic in the treatment of adult neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, ischemic stroke, traumatic brain injury, and Parkinson’s disease. Recent advances …

Immunomodulation With Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis, Maple L. Shiao, Ce Yuan, Andrew T. Crane, Joseph P. Voth, Mario Juliano, Laura L. Hocum Stone, Zhenghong Nan, Ying Zhang, Nicole Kuzmin-Nichols, Paul R. Sanberg, Andrew W. Grande, Walter C. Low

Neurosurgery and Brain Repair Faculty Publications

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that …

Administration Of Rctrp9 Attenuates Neuronal Apoptosis Through Adipor1/Pi3k/Akt Signaling Pathway After Ich In Mice, Lianhua Zhao, John H. Zhang, Prativa Sherchan, Paul R. Krafft, Wei Zhao, Sa Wang, Shengpan Chen, Zaiyu Guo, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were …

Retrospective Case Series Of Traumatic Brain Injury And Post-Traumatic Stress Disorder Treated With Hyperbaric Oxygen Therapy, R. Douglas Shytle, David J. Eve, Soel-Hee Kim, Allan Spiegel, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Returning veterans are frequently diagnosed with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Considering a recent case-controlled study of hyperbaric oxygen therapy (HBOT) reporting a reduction in suicidal ideation, we investigated retrospectively three veterans with chronic TBI/PTSD symptoms who were treated with multiple rounds of HBOT with neurophysiological testing performed before and after treatment. Improvements were detected on parameters within neurocognitive domains, including reductions in suicide-related symptoms. These findings independently confirm that HBOT may be effective in treating specific symptoms of TBI/PTSD that are not currently addressed with existing therapeutic approaches.

Wire Guided Cannulation Facilitates Endoscopic Management Of Buried Bumper Syndrome: A Novel Technique, Jacquelin Peck, Kaitlin Sapp, Alexander Wilsey, Michael Wilsey

Pediatrics Faculty Publications

Buried bumper syndrome is a rare but potentially severe complication of percutaneous endoscopic gastrostomy tube insertion. Though this complication is uncommon, it may lead to pressure necrosis, bleeding, perforation, peritonitis, sepsis, or death. Each case of buried bumper syndrome is unique in terms of patient comorbidities and anatomic positioning of the buried bumper. For this reason, many approaches have been described in the management of buried bumper syndrome. In this case report, we describe the case of an adolescent Caucasian female who developed buried bumper syndrome three years after undergoing percutaneous endoscopic gastrostomy insertion. We review diagnosis and management of …

Down The Rabbit Hole-Considerations For Ingested Foreign Bodies, Jerry Brown, Molly Kidder, Abigail Fabbrini, Jonathan Devries, Jason Robertson, Nicole Chandler, Michael Wilsey

Pediatrics Faculty Publications

We report the case of a seven-year-old boy with an ingested foreign body, which was retained within the appendix for a known duration of ten months, ultimately requiring appendectomy. The ingested foreign body was incidentally discovered by abdominal x-ray at an emergency room visit for constipation. Despite four bowel cleanouts, subsequent x-rays showed persistence of the foreign body in the right lower quadrant. While the patient did not have signs or symptoms of acute appendicitis, laparoscopic appendectomy was performed due to the risk of this foreign body causing appendicitis in the future. A small metallic object was found within the …

Lamotrigine Odt-Induced Seizure In A 3-Year-Old Child After Accidental Ingestion, Ashley Griswold, Briana Tully, Kenneth Katz, Gillian Beauchamp, Matthew Cook, Robert Cannon

Pediatrics Faculty Publications

Lamotrigine is a new generation antiepileptic which blocks sodium channels and can cause significant toxicity in overdose. A case of a three-year-old child who suffered a seizure and required endotracheal intubation after accidental lamotrigine ingestion is presented. The lamotrigine concentration measured 23.2 mcg/mL which is the highest reported after accidental pediatric exposure. A review of the literature regarding pediatric lamotrigine poisoning is also included.

Ampk: A Balancer Of The Renin–Angiotensin System, Jia Liu, Xuan Li, Qingguo Lu, Di Ren, Xiaodong Sun, Thomas Rousselle, Ji Li, Jiyan Leng

Surgery Faculty Publications

The renin–angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves …

Factors Associated With Chest Tube Placement In Blunt Trauma Patients With An Occult Pneumothorax, Michael Paplawski, Swapna Munnangi, Jody C. Digiacomo, Edwin Gonzalez, Ashley Modica, Shawndeep S. Tung, Catherine Ko

Surgery Faculty Publications

Background. An occult pneumothorax is identified by computed tomography but not visualized by a plain film chest X-ray. The optimal management remains unclear. Methods. A retrospective review of an urban level I trauma center’s trauma registry was conducted to identify patients with occult pneumothorax over a 2-year period. Factors predictive of chest tube placement were identified using univariate and multivariate logistic regression analysis. Results. A total of 131 patients were identified, of whom 100 were managed expectantly with an initial period of observation. Ultimately, 42 (32.0%) patients received chest tubes and 89 did not. The patients who …