Digital Commons Network^™

Loss Of Hif-1Α In The Notochord Results In Cell Death And Complete Disappearance Of The Nucleus Pulposus., Christophe Merceron, Laura Mangiavini, Alexander Robling, Tremika Leshan Wilson, Amato J Giaccia, Irving Shapiro, Ernestina Schipani, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF). This structure is covered superior and inferior side by cartilaginous endplates (CEP). The NP is a unique tissue within the IVD as it results from the differentiation of notochordal cells, whereas, AF and CEP derive from the sclerotome. The hypoxia inducible factor-1α (HIF-1α) is expressed in NP cells but its function in NP development and homeostasis is …

Nutrition And Prevention Of Alzheimer's Dementia, Arun Swaminathan, Gregory A. Jicha

Neurology Faculty Publications

A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer’s dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may …

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …

Experimental Study Of Needle-Tissue Interaction Forces: Effect Of Needle Geometries, Insertion Methods And Tissue Characteristics., Shan Jiang, Pan Li, Yan Yu, Jun Liu, Zhiyong Yang

Department of Radiation Oncology Faculty Papers

A thorough understanding of needle-tissue interaction mechanics is necessary to optimize needle design, achieve robotically needle steering, and establish surgical simulation system. It is obvious that the interaction is influenced by numerous variable parameters, which are divided into three categories: needle geometries, insertion methods, and tissue characteristics. A series of experiments are performed to explore the effect of influence factors (material samples n=5 for each factor) on the insertion force. Data were collected from different biological tissues and a special tissue-equivalent phantom with similar mechanical properties, using a 1-DOF mechanical testing system instrumented with a 6-DOF force/torque (F/T) sensor. The …

Gucy2c Lysosomotropic Endocytosis Delivers Immunotoxin Therapy To Metastatic Colorectal Cancer., Glen P Marszalowicz, Adam E. Snook, Michael Sullivan Magee, Dante Merlino, Lisa D Berman-Booty, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for …

Visualization-Aided Classification Ensembles Discriminate Lung Adenocarcinoma And Squamous Cell Carcinoma Samples Using Their Gene Expression Profiles, Ao Zhang, Chi Wang, Shiji Wang, Liang Li, Zhongmin Liu, Suyan Tian

Markey Cancer Center Faculty Publications

INTRODUCTION: The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC), there are two major histological types of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC).

RESULTS: In this paper, we proposed to integrate a visualization method called Radial Coordinate Visualization (Radviz) with a suitable classifier, aiming at discriminating two NSCLC subtypes using patients' gene expression profiles. Our analyses on simulated data and a real microarray dataset show that combining with a classification method, Radviz may play a role in …

Cerebral Arteriovenous Malformations: Evaluation And Management., Norman Ajiboye, Nohra Chalouhi, Md, Robert M Starke, Mario Zanaty, Rodney Bell, Md

Department of Neurosurgery Faculty Papers

There has been increased detection of incidental AVMs as result of the frequent use of advanced imaging techniques. The natural history of AVM is poorly understood and its management is controversial. This review provides an overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management of AVMs. The authors discussed the imaging techniques available for detecting AVMs with regard to the advantages and disadvantages of each imaging modality. Furthermore, this review paper discusses the factors that must be considered for the most appropriate management strategy (based on the current evidence in the literature) and the risks and benefits …

Tp53 Mutations Detected In Circulating Tumor Cells Present In The Blood Of Metastatic Triple Negative Breast Cancer Patients., Sandra V Fernandez, Catherine Bingham, Patricia Fittipaldi, Laura Austin, Juan P. Palazzo, Gary Palmer, Katherine Alpaugh, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Circulating tumor cells (CTCs) are tumor cells shed from either primary tumors or its metastases that circulate in the peripheral blood of patients with metastatic cancers. The molecular characterization of the CTCs is critical to identifying the key drivers of cancer metastasis and devising therapeutic approaches. However, the molecular characterization of CTCs is difficult to achieve because their isolation is a major technological challenge.

METHODS: CTCs from two triple negative breast cancer patients were enriched using CellSearch and single cells selected by DEPArray™. A TP53 R110 fs*13 mutation identified by next generation sequencing in the breast and chest skin …

Curcumin-Induced Heme Oxygenase-1 Expression Prevents H2o2-Induced Cell Death In Wild Type And Heme Oxygenase-2 Knockout Adipose-Derived Mesenchymal Stem Cells., Niels A J Cremers, Ditte M S Lundvig, Stephanie C M Van Dalen, Rik F Schelbergen, Peter L E M Van Lent, Walter A Szarek, Raymond F. Regan, Carine E Carels, Frank A D T G Wagener

Department of Emergency Medicine Faculty Papers

Mesenchymal stem cell (MSC) administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO) generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO) and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs) from wild type (WT) and HO-2 knockout (KO) mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC …

Breast Cancer Incidence And Mortality In A Transitioning Chinese Population: Current And Future Trends, O. L. Wong, Mary Schooling, Benjamin J. Cowling, Gabriel M. Leung

Publications and Research

Background Projections of future trends in cancer incidence and mortality are important for public health planning. Methods By using 1976–2010 data in Hong Kong, we fitted Poisson age-period-cohort models and made projections for future breast cancer incidence and mortality to 2025. Results Age-standardised breast cancer incidence (/mortality) is projected to increase (/decline) from 56.7 (/9.3) in 2011–2015 to 62.5 (/8.6) per 100 000 women in 2021–2025. Conclusions The incidence pattern may relate to Hong Kong’s socio-economic developmental history, while falling mortality trends are, most likely, due to improvements in survival from treatment advancement and improved health service delivery.

Self-Reported Memory Complaints: Implications From A Longitudinal Cohort With Autopsies, Richard J. Kryscio, Erin L. Abner, Gregory E. Cooper, David W. Fardo, Greg A. Jicha, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.

METHODS: Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).

RESULTS: SMCs were …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …

The Pathophysiology Of Tumor Lysis Syndrome In Oncology Patients, Jessica Richardson

Nursing Student Class Projects (Formerly MSN)

Patients with oncological conditions are at an increased risk of developing a wide variety of complications from chemotherapy that they would not otherwise be exposed too. One such life threatening complication is tumor lysis syndrome, which is an oncology emergency that frequently lands patients in the intensive care unit. Tumor lysis syndrome (TLS) occurs most frequently after the initiation of chemotherapy or other chemotoxic drugs during the patients’ treatment course [8]. It causes faster than normal tumor cell breakdown and release of intracellular contents into the general circulation. [8]. This leads to a very predictable development of electrolyte imbalances to …

Understanding The Mystery Of Brain Death, Natalie A. Felter

Nursing Student Class Projects (Formerly MSN)

Lack of understanding of brain death has contributed to recent controversial cases (Copnell, 2014). The cases of Jahi McMath and Marlise Munoz were the focus of national news, causing an intense debate among the public and healthcare professionals (Copnell, 2014). The concept of brain death is a mystery to the public (Powell, 2014). Copnell (2014) found that 60% of family members who had been told their loved one was brain dead believed that they were still alive. Health professionals not having a clear grasp of brain death’s definition and assessment can lead to increased confusion in family members (Powell, 2014).

Neonatal Nmda Receptor Blockade Disrupts Spike Timing And Glutamatergic Synapses In Fast Spiking Interneurons In A Nmda Receptor Hypofunction Model Of Schizophrenia, Kevin S. Jones, Joshua G. Corbin, Molly M. Huntsman

Pediatrics Faculty Publications

The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI) is considered a primary contributor to the pathophysiology of schizophrenia (SZ), but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice …

Effect Of Age On Uterine And Ovarian Morphology With Polycystic Ovaries, Ambreen Usmani, Rehana Rehman, Aisha Qamar

Department of Biological & Biomedical Sciences

Abstract

Objective: To measure the outcome of age on ovarian and uterine morphology in primary infertile women with

polycystic ovaries.

Methods: The observational cross-sectional study was conducted from January 2009 to March 2010, and the

subjects were recruited from Ziauddin Hospital, Nazimabad, Karachi. The primary infertile subjects with polycystic

ovaries were subdivided into two age groups:20-30 years (group I), and 31-40 years (group II). Both groups had equal

number of subjects. The ovarian volume, follicles count and size, uterine area and endometrial thickness were

determined by transabdominal and transvaginal scans. Shapiro-Wilk's test and Mann-Whitney test were applied,

with p<0.05 being significant.

Results: …

Oncolog, Volume 59, Number 10, October 2014, Sarah Bronson, Kathryn L. Hale, Roberto Molar-Candanosa, K. Stuyck

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• New Drugs for Myeloproliferative Neoplasms Ease Suffering and Extend Life: A new class of drugs has redefined treatment for patients with myeloproliferative neoplasms by easing their symptom burden while extending their lives
• Neoadjuvant Targeted Therapy May Offer Multiple Benefits for Patients with Locally Advanced Renal Cancer: Despite definitive treatment with nephrectomy, locally advanced renal cancer recurs in 20%-30% of patients, substantially reducing their chance for long-term survival. To prevent such recurrences and prolong survival, urologic oncologists are studying the integration of targeted molecular therapies with surgical treatments
• New Combination Therapy Offers Potential to Cure FLT3-ITD Acute Myelogenous Leukemia: A new …

Rationale And Design Of The Guide-It Study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment In Heart Failure., G. Michael Felker, Tariq Ahmad, Kevin J. Anstrom, Kirkwood F. Adams, Lawton S. Cooper, Justin A. Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, James L. Januzzi, Eric S. Leifer, Daniel B. Mark, Patrice Desvigne-Nickens, Gayle Paynter, Ileana L. Piña, David J. Whellan, Christopher M. O'Connor

Division of Cardiology Faculty Papers

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of

BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies …

Evaluating Initial Spine Trauma Response: Injury Time To Trauma Center In Pa, Usa., James Harrop, Md, George M. Ghobrial, Md, Rohan Chitale, Md, Kelly Krespan, Laura Odorizzi, Tristan Fried, Mitchell Maltenfort, Phd, Murray Cohen, Md, Alex R. Vaccaro, Md

Department of Neurosurgery Faculty Papers

Historical perceptions regarding the severity of traumatic spinal cord injury has led to considerable disparity in triage to tertiary care centers. This article retrospectively reviews a large regional trauma database to analyze whether the diagnosis of spinal trauma affected patient transfer timing and patterns. The Pennsylvania Trauma database was retrospectively reviewed. All acute trauma patient entries for level I and II centers were categorized for diagnosis, mechanism, and location of injury, analyzing transportation modality and its influence on time of arrival. A total of 1162 trauma patients were identified (1014 blunt injuries, 135 penetrating injuries and 12 other) with a …

Identification And Characterization Of Protein Kinase C Substrates In Human Breast Cells, Xin Zhao

Dissertations, Theses, and Capstone Projects

Aberrations in PKC signaling can lead to the development of multiple human diseases and the most prominent association of PKC with disease has been in tumor growth and metastasis. PKC and its related pathways have been recognized as promising targets for blocking the malignancy of breast cancer cells. To better understand PKC-mediated pathway in breast cancer cells, it is important to identify the cellular substrates of PKC. The main focus of this work is to identify physiologically relevant cellular substrates of PKC in human breast cells and to characterize their roles in cancer-related phenotypes. The work to be described consists …

Surgeon Practices And Attitudes Toward The Control Of Surgical-Site Infections In Jordan, Sara Ali Mater

Independent Study Project (ISP) Collection

The purpose of this study was to determine the attitudes and practices of Jordanian surgeons on the control of surgical-site infections, evaluated by the Center of Disease Control’s guidelines toward the prevention of surgical-site infections, in addition to gaining respondents opinions on infection control in Jordan. This study was conducted through the distribution of 75 questionnaires given to surgeons at five hospitals in Jordan. Additional insight on SSI infection control was gained through interviews with two cardiac surgeons and three infection control directors. The results of the survey were compared with the Center for Disease Control’s guide to surgical-site infection …

Palliative Care's Sacramental And Liturgical Foundations: Healthcare Formed By Faith, Hope, And Love, Darren M. Henson

Dissertations (1934 -)

Medical history identifies Dame Cicely Saunders as the founder of modern hospice and palliative care for the unique care she gave to the incurably and terminally ill. Less known is how her Christian faith, combined with her knowledge of medicine, influenced her vision. This work retrieves the Christian roots of palliative care and asserts that the practice of faith preserves the practice of medicine from succumbing to medicalized dying--a phenomenon that excessively relies on technology with the implied hope that it will ultimately conquer illnesses and even death. Efficiency and effectiveness ground modern medicine's epistemology. These concepts follow the philosophical …

Analysis Of Candidate Genes Has Proposed The Role Of Y Chromosome In Human Prostate Cancer, Pegah Khosravi, Javad Zahiri, Vahid H. Gazestani, Samira Mirkhalaf, Mohammad Akbarzadeh, Mehdi Sadeghi, Bahram Goliaei

Publications and Research

Background: Prostate cancer, a serious genetic disease, has known as the first widespread cancer in men, but the molecular changes required for the cancer progression has not fully understood. Availability of high-throughput gene expression data has led to the development of various computational methods, for identification of the critical genes, have involved in the cancer. Methods: In this paper, we have shown the construction of co-expression networks, which have been using Y-chromosome genes, provided an alternative strategy for detecting of new candidate, might involve in prostate cancer. In our approach, we have constructed independent co-expression networks from normal and cancerous …

Effect Of Obesity And Exercise On The Expression Of The Novel Myokines, Myonectin And Fibronectin Type Iii Domain Containing 5, Jonathan M. Peterson, Ryan Mart, Cherie E. Bond

ETSU Faculty Works

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, …

Isomir Expression Profiles In Human Lymphoblastoid Cell Lines Exhibit Population And Gender Dependencies., Phillipe Loher, Eric R Londin, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

For many years it was believed that each mature microRNA (miRNA) existed as a single entity with fixed endpoints and a 'static' and unchangeable primary sequence. However, recent evidence suggests that mature miRNAs are more 'dynamic' and that each miRNA precursor arm gives rise to multiple isoforms, the isomiRs. Here we report on our identification of numerous and abundant isomiRs in the lymphoblastoid cell lines (LCLs) of 452 men and women from five different population groups. Unexpectedly, we find that these isomiRs exhibit an expression profile that is population-dependent and gender-dependent. This is important as it indicates that the LCLs …

The Association Of Meningococcal Disease With Influenza In The United States, 1989-2009, Jessica Hartman Jacobs, Cecile Viboud, Eric Tchetgen Tchetgen, Joel Schwartz, Claudia Steiner, Lone Simonsen, Marc Lipsitch

Global Health Faculty Publications

Importance and Objective

Prior influenza infection is a risk factor for invasive meningococcal disease. Quantifying the fraction of meningococcal disease attributable to influenza could improve understanding of viral-bacterial interaction and indicate additional health benefits to influenza immunization.

Design, Setting and Participants

A time series analysis of the association of influenza and meningococcal disease using hospitalizations in 9 states from 1989–2009 included in the State Inpatient Databases from the Agency for Healthcare Research and Quality and the proportion of positive influenza tests by subtype reported to the Centers for Disease Control. The model accounts for the autocorrelation of meningococcal disease and …

Plasma Adiponectin, Clinical Factors, And Patient Outcomes During The Acute Respiratory Distress Syndrome., Allan J Walkey, Serkalem Demissie, Dilip Shah, Freddy Romero, Leah Puklin, Ross S Summer

Center for Translational Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).

METHODS: We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.

RESULTS: Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, …

Development Of A Fatal Noncompressible Truncal Hemorrhage Model With Combined Hepatic And Portal Venous Injury In Normothermic Normovolemic Swine, Ujwal R. Yanala, Jason M. Johanning, Iraklis I. Pipinos, Gustavo F. Larsen, William H. Velander, Mark A. Carlson

William H. Velander Publications

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ,50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34–36 kg) underwent one of three injury types …

Transformation Of Human Cathelicidin Ll-37 Into Selective, Stable, And Potent Antimicrobial Compounds., Guangshun Wang, Mark L. Hanke, Biswajit Mishra, Tamara Lushnikova, Cortney E. Heim, Vinai Chittezham Thomas, Kenneth W. Bayles, Tammy Kielian

Journal Articles: Pathology and Microbiology

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide …