Medicine and Health Sciences Commons^™

Protocol And Design Of The Repose Study: A Double-Blinded, Randomised, Placebo-Controlled Trial To Evaluate The Efficacy Of Suvorexant To Improve Postoperative Sleep And Reduce Delirium Severity In Older Patients Undergoing Non-Cardiac Surgery, John Michael Fallon, Mona Hashemaghaie, Christy E. Peterson, Dieplinh Tran, Sophie R. Wu, Jonathan M. Valdes, Nicole M. Pedicini, Melissa E. Adams, Marjorie Soltis, Wissam Mansour, Mary Cooter Wright, Karthik Raghunathan, Miriam M. Treggiari, Cina Sasannejad, Michael J. Devinney

School of Medicine Faculty Publications

INTRODUCTION: Postoperative delirium occurs in up to 40% of older surgical patients and has been associated with prolonged hospital stays, long-term cognitive impairment and increased 1-year postoperative mortality. Postoperative sleep disturbances may increase the risk of delirium, but studies investigating pharmacotherapies to improve postoperative sleep to prevent delirium remain limited. Suvorexant is a selective antagonist of orexin 1 and 2 receptors and is approved for insomnia pharmacotherapy by the Food and Drug Administration. It has the potential to improve postoperative sleep and reduce postoperative delirium rates, but randomised controlled trials (RCTs) are needed to determine the efficacy of postoperative suvorexant …

Second-Site Periprosthetic Joint Infection After Subsequent Primary Hip Or Knee Arthroplasty: Risk Factor Assessment, Daniel Aris Nikolaidis, Devin Young, Robert Runner, Mark S. Karadsheh, Andrew Steffensmeier

Conference Presentation Abstracts

INTRODUCTION: The risk factors for developing a periprosthetic joint infection (PJI) are well described. However, those associated with developing a second-site or metachronous PJI (MPJI) following a subsequent primary arthroplasty are poorly understood. The purpose of our study is to determine (1) prevalence and (2) risk factors associated with developing a second-site PJI in patients with a prior history of PJI who undergo a subsequent THA or TKA. METHODS: A retrospective, single-center case-control study identified 77 patients treated for an index PJI (hip or knee) between 2013-2022, and who also underwent another primary arthroplasty after completing treatment for their first …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Deep Learning Models Based On Pretreatment Mri And Clinicopathological Data To Predict Responses To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Zhan Xu, Zijian Zhou, Jong Bum Son, Haonan Feng, Beatriz E Adrada, Tanya W Moseley, Rosalind P Candelaria, Mary S Guirguis, Miral M Patel, Gary J Whitman, Jessica W T Leung, Huong T C Le-Petross, Rania M Mohamed, Bikash Panthi, Deanna L Lane, Huiqin Chen, Peng Wei, Debu Tripathy, Jennifer K Litton, Vicente Valero, Lei Huo, Kelly K Hunt, Anil Korkut, Alastair Thompson, Wei Yang, Clinton Yam, Gaiane M Rauch, Jingfei Ma

Faculty, Staff and Student Publications

Purpose: To develop deep learning models for predicting the pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in patients with triple-negative breast cancer (TNBC) based on pretreatment multiparametric breast MRI and clinicopathological data.

Methods: The prospective institutional review board-approved study [NCT02276443] included 282 patients with stage I-III TNBC who had multiparametric breast MRI at baseline and underwent NAST and surgery during 2016-2021. Dynamic contrast-enhanced MRI (DCE), diffusion-weighted imaging (DWI), and clinicopathological data were used for the model development and internal testing. Data from the I-SPY 2 trial (2010-2016) were used for external testing. Four variables with a …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Cranial Radiation Disrupts Dopaminergic Signaling And Connectivity In The Mammalian Brain, Die Zhang, Riya Thomas, Thanh Thai Lam, Ines Veselinovic, David R Grosshans

Faculty, Staff and Student Publications

Cognitive impairment is a common and challenging side effect of cranial radiation therapy for brain tumors, though its precise mechanisms remain unclear. The mesocortical dopaminergic pathway, known to play a key role in cognitive function, is implicated in several neuropsychiatric disorders, yet its involvement in radiation-induced cognitive dysfunction is unexplored. Here, with using in vivo multi-electrode array recordings of both anesthetized and free-moving rats to monitor the firing activities of dopamine neurons in the ventral tegmental area (VTA) and local field potentials in both the prefrontal cortex (PFC) and VTA, as well as the immunofluorescence assays and western blotting, we …

Increasing Patient Age And General Anesthesia Are Risk Factors For Failure Of Same-Day Discharge Total Hip Arthroplasty, Kevin Xavier Farley, Robert Dean, Mark S. Karadsheh, Drew Douglas Moore

Conference Presentation Abstracts

INTRODUCTION: As cost containment efforts in orthopedic surgery increase, there has been a rise in same-day discharge total hip arthroplasty (THA). Same-day discharge THA has been further accelerated by the COVID-19 pandemic and the removal of THA from the Medicare inpatient only list. This study sought to evaluate risk factors for readmission following same-day discharge THA. METHODS: From 2012-2021, the National Surgical Quality Improvement Project database was used to identify all patients undergoing elective THA discharged the day of surgery to their home. Demographic, comorbid, and operative variables were collected, as displayed in Table 1. Readmission within 30-days of surgery …

Influence Of Marching Band Experience On Eating Disorder Risk And Perceived Stress In Collegiate Marching Artists, Kalor Greve, Jaclyn B. Caccese, Matthew P. Brancaleone

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: Collegiate marching artists face severe and prevalent stressors that may contribute to poor mental health and unhealthy habits. The purpose of this study was to determine the effect of sex and years of participation in collegiate marching band on the relationship between eating disorder risk and perceived stress levels. Methods: Marching artists from an NCAA Division I university completed the Eating Disorder Questionnaire-6 (EDEQ-6) and Perceived Stress Scale (PSS-10) to obtain disordered eating behaviors and perceived stress levels, respectively. Spearman rank correlations were used to determine the relationship between PSS-10 scores and global and subscale EDEQ-6 scores, …

Barriers To The Implementation Of The Amsterdam 2022 Statement In The Secondary School Setting, Luis Torres, Jennifer L. Baldari, Fredrick A. Gardin, August M. Price

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: Athletic trainers are reasonably expected to evolve their concussion management protocols to better align themselves with the recommendations found in the Amsterdam 2022 Statement. Secondary school athletic trainers may lack the time, training, or resources to actualize these recommendations within their protocols. The purpose of this study was to identify the barriers associated with the implementation of the Amsterdam 2022 Statement recommendations in the secondary school setting. Methods: 89 secondary school ATs (44 males, 45 females) in the NATA District 1 and District 2 regions were provided with an electronic survey using Qualtrics (Qualtrics, Provo, UT), consisting of 6 …

Identifying Factors Associated With Sleep Disorders And Treatment Avoidance Among Collegiate Student-Athletes, Allie Ziniti, Andrew W. Froehle, Brian A. Edwards

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: Mental health concerns among collegiate students-athletes are exacerbated by poor sleep, and this population experiences elevated risk for irregular sleep patterns and associated sleep disorders. Interventions aimed at early identification of student-athletes experiencing sleep disorders and guiding them to treatment can contribute to improved mental health in this group. The present study’s objective was to clarify risk-factors associated with increased likelihood of sleep disorders and treatment avoidance in student-athletes. Methods: Data were self-reported survey responses related to sleep disorders, from US college/university varsity athletes (n=51,882) completing the 2011-2019 National College Health Assessments (NCHA). Outcomes: The primary outcomes that we …

Access To Outreach Athletic Trainers Improves Orthopedic Specialty Appointment Adherence, Katie Sniffen, Katie Smith, Michael Rozier, Katherine Stamatakis, Paula Buchanan, Leslie Hinyard

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Background: Adolescent sports participation carries an inherent risk of musculoskeletal injury, with an estimated 2 million injuries occurring annually among high school athletes. Navigating the healthcare system to receive appropriate care can be challenging, potentially leading to delayed treatment and poorer outcomes. Athletic trainers (ATs) may play a crucial role in facilitating timely access to specialized care. The objective of this study was to assess the relationship between referral pathways (outreach athletic trainers (OATs), non-outreach athletic trainers (ATs), urgent care (UC), and emergency department (ED)) and appointment adherence while controlling for predisposing, enabling, and need factors. Methods: Using electronic medical …

Retention Of Cpr Knowledge And Skills Among Ncaa Division Iii Athletic Coaches: A Prospective Cohort Study, Allison Hanstine, Jaclyn Tate, Chyrsten Gessel

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Objective/Context: It is crucial for athletic coaches to be proficient in cardiopulmonary resuscitation (CPR) knowledge and skill performance for the health and safety of their athletes. This research aimed to assess CPR knowledge and CPR skill retention five months post-training among athletic coaches. In addition, the study assessed whether the number of years certified in CPR had an association with CPR skill performance scores five months post-training. Design and Setting: As a part of a master’s thesis, this prospective cohort study was performed over a five-month period to align with the research timeline. Participants: The study was conducted among 19 …

A Pilot Study: Effects Of 5-Week Hamstring Training On Functional Movement Screen Scores., Julie Landrigan, Colin Tomes

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction. The Functional Movement Screen (FMS) can be used by clinicians to assess movement and asymmetries in their clients. Understanding FMS composite and subtest scores can be a useful way for clinicians to monitor risk of injury. The purpose of this study was to identify if eccentric hamstring stretching and Nordic hamstring curls could improve movement, FMS scores, and active straight leg raise range of motion. Methods. Participants consisted of a convenience sample of high-school athletes. All subjects participated in the intervention, performing the FMS screen pre- and post-Nordic curls and stretching. Results. This pilot study suggests that the …

Normative Performance Test Metrics In Professional Female Club Soccer, Andy Seraphin, Christi Edson, Cory Price, Barrett Jones, Amanda Jagielo, Justin Mullner

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Objective: To establish normative ranges in common performance tests for professional women’s club soccer. Setting:1^st division professional women’s soccer club in the United States

Participants: Twenty-eight healthy professional women’s soccer players (Age: 27.8 ± 5.1 years; Body Mass: 66.2 ± 6.7 kg). Main Outcome Measures: Countermovement Jump, Isometric Mid-Thigh Pull, and Nordic Hamstring Curl tests were performed to obtain lower body compound strength, power, and eccentric hamstring strength. Paired-samples t tests were used to determine between-limbs differences for each outcome measure. Results: Jump height had a mean of 28.9 ± 4.2 cm. Peak vertical force (IMTP) had a …

Relationship Between E-Sports And Physical Activity Participation: Validation Of The E-Sports Addiction Scale (Esas), Olivér Szabella, Lili Kassay, Attila Szabo

Baltic Journal of Health and Physical Activity

Background: E-sports are becoming increasingly popular. Considering the addictive potential of video games, e-sports might be more addictive than traditional sports. This study assessed the addiction risk in regular e-sports players and its relationship with other physical exercise habits. Method: A sample of 116 (93.1% males; mean age = 23.91±4.47) e-sports players answered questions online on play and exercise habits and completed the E-sports Addiction Scale (ESAS) derived from the revised Exercise Addiction Inventory (EAI-R). Results: The ESAS showed excellent model fit, allowing researchers to assess the risk of e-sports addiction in future studies. The risk rate of e-sports addiction …

Reliability And Criterion Validity Of The Turkish Version Of The Recent Physical Activity Questionnaire, Kubra Ayse Dasdemir, Sinem Suner-Keklik, Gamze Cobanoglu, Nevin A. Guzel

Baltic Journal of Health and Physical Activity

Background: This study aims to determine reliability and criterion validity of the Turkish version of the Recent Physical Activity Questionnaire (RPAQ). Materials and methods: The study included 146 individuals aged 18–45 years. Translation and cultural adaptation of the questionnaire was performed with regard to an appropriate procedure. Test–retest reliability was analyzed in terms of intraclass correlation coefficient (ICC). For assessment of validity of the questionnaire, the criterion validity method was used. Criterion validity was evaluated using a pedometer, which is an objective measurement tool. The correlation between the total number of steps recorded during a week and RPAQ scores was …

Impact Of A Three-Week Full Leg Cast Immobilization On Infant Crawling Kinetics And Spatiotemporal Parameters, Mark Daniel Geil

Faculty Articles

Despite its importance in the development of mobility in infants, there is a general lack of quantified data on infant crawling, and a specific lack of understanding of crawling kinetics, which includes the relative weightbearing and force generation among the four limbs. Moreover, because of the difficulty of measurement and study design, there is no longitudinal quantification of the impact of a perturbation to typical development, such as limb immobilization. This study measured kinetic and spatiotemporal outcomes in a typically developing infant prior to a fracture that necessitated a long-leg cast that immobilized the left knee and ankle, while crawling …

Epigastric Hernia Containing Incarcerated Gallbladder, Katelyn R. Ward, Melanie Ermler, Kathryn M. Ziegler

Conference Presentation Abstracts

Introduction: Epigastric hernias represent 1.6–3.6% of all abdominal hernias, and usually contain preperitoneal fat and occasionally omentum or small bowel. Rarely, epigastric hernias may contain portions of other organs, such as colon or stomach. We report an unusual case of a patient whose incarcerated epigastric hernia contained her stone-filled gallbladder.over a million performed in the US, and over 20 million worldwide annually. We aim to study and compare interest trends in the US and the World for IHR techniques (open, laparoscopic, robotic) using GT. Methods: The following search topics were analyzed from January 2010 to August 2024 in ‘‘US’’ and …

Neuraxial Vs. General Anesthesia In Total Hip Arthroplasty For Femoral Neck Fracture: A Comparison Of Post-Operative Complications, Kevin Xavier Farley, Robert Dean, Mark S. Karadsheh, Drew Douglas Moore

Conference Presentation Abstracts

INTRODUCTION: Rates of complications with differing anesthetic choices has not been directly compared for patients undergoing total hip arthroplasty (THA) for femoral neck fractures. This study sought to directly compare neuraxial vs. general anesthetic use and compare post-operative outcomes for patients undergoing THA for a femoral neck fracture. METHODS: From 2012-2021, the National Surgical Quality Improvement Project (NSQIP) database was used to identify all patients undergoing THA for a femoral neck fracture. Anesthetic type was identified and categorized as neuraxial (spinal, epidural) or general. Demographic and comorbid variables were collected. Days from admission to surgery was also identified. Postoperative complications …

The Role Of Electrophysiologic Study In Device Selection For Leadless Atrial Pacing, Joshua R Hirsch, Jordan M Gales, Irakli Giorgberidze, Hamid Afshar

The Texas Heart Institute Journal

The AVEIR DR (Abbott Medical) was the first dual-chamber leadless pacing system approved by the US Food and Drug Administration. Many patients with sinus node dysfunction have physiologically normal atrioventricular conduction, so an atrial-only pacing system may be appropriate for them. Three patients with symptomatic sinus node dysfunction underwent device implantation with electrophysiologic study, including incremental atrial pacing until loss of 1:1 atrioventricular conduction (atrioventricular Wenckebach cycle length) and His-ventricular interval measurement. If the atrioventricular Wenckebach cycle length was no more than 400 milliseconds and the His-ventricular interval measurement was no more than 55 milliseconds, single-chamber atrial implantation was deemed …

Control Of Clostridioides Difficile Virulence And Physiology By The Flagellin Homeostasis Checkpoint Flic-Fliw-Csra In The Absence Of Motility, Duolong Zhu, Katherine J Wozniak, Firas Midani, Shaohui Wang, Xingmin Sun, Robert A Britton

Faculty, Staff and Students Publications

Mutations affecting Clostridioides difficile flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving fliC, fliW, and csrA, which creates a feedback system to regulate flagella production. Through genomic analysis of C. difficile clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene fliC and regulatory gene fliW. We therefore investigated the roles of fliC, fliW …

Left Behind: A Rare Case Of True Gallbladder Sinistroposition And Surgical Implications, Daniel Finn, Jacob Applegarth, Jacob Mesiti, Mario Villalba

Conference Presentation Abstracts

Objectives: Encountering aberrant biliary anatomy is a known risk factor for inadvertent injury while performing biliary surgery. One described anatomic aberrancy, sinistroposition of the gallbladder (also known as ‘‘left sided gallbladder’’), is a rarely seen anatomic abnormality with an incidence of 0.2% to 1.1%. Given the infrequent encounters with this abnormality and its association with other anatomic anomalies, extreme care and caution should be exercised when performing a cholecystectomy in this patient population. Methods: We present the case of a 37-year-old male who presented with abdominal pain and was diagnosed with Tokyo Grade I acute calculous cholecystitis. An ultrasound of …

The Dnase Trex1 Is A Substrate Of The Intramembrane Protease Spp With Implications For Disease Pathogenesis, Onur Kerem Tever, Torben Mentrup, Ivan Kingyue Chinn, Hitoshi Ishikuma, Regina Fluhrer, Marc Schmitz, Rebekka Wehner, Rayk Behrendt, Javier Chinen, Bernd Schröder

Faculty, Staff and Students Publications

Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway. TREX1 loss-of-function variants cause Aicardi-Goutières syndrome (AGS), a type I interferonopathy. Cleavage of ER-bound TREX1 by SPP releases a cleavage product into the cytosol. Proteolysis depends on sequence determinants within the transmembrane segment and is modulated by different disease-associated TREX1 variants. The AGS-causing T303P variant greatly …

Two-Dimensional Preoperative Digital Templating Is Less Accurate When Using A Collared Triple Taper Stem Versus A Single Taper Design, Claudio Diaz-Ledezma, Angel X. Xiao, Juan David Lizcano, Erik N. Hansen, Camilo Restrepo, William J. Hozack

Rothman Institute Papers

Background

Collared triple taper stems (CTTS) and single taper stems (STS) have an excellent performance in primary total hip arthroplasty (THA). While 2-dimensional radiographic templating is accurate for STS, data are lacking for CTTS. We hypothesize that CTTS’ more anatomical design in the anteroposterior dimension may lead to inaccurate templating sizing. This study compared templating accuracy of CTTS to a predecessor STS in THA patients.

Methods

106 THA performed with CTTS were compared to 106 THA performed with STS by 2 high-volume surgeons. The stems chosen for comparison were manufactured by the same company, use the same templating software, shared …

Alpha-Frequency Stimulation Strengthens Coupling Between Temporal Fluctuations In Alpha Oscillation Power And Default Mode Network Connectivity, Yijia Ma, Joshua A Brown, Chaowen Chen, Mingzhou Ding, Wei Wu, Wen Li

Faculty, Staff and Student Publications

Alpha (8–12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram (EEG)/magnetoencephalogram and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG–fMRI data acquired before and …

Advancing Drug Development In Myelodysplastic Syndromes, Alain Mina, Kathy L Mcgraw, Lea Cunningham, Nina Kim, Emily Y Jen, Katherine R Calvo, Lori A Ehrlich, Peter D Aplan, Guillermo Garcia-Manero, James M Foran, Jacqueline S Garcia, Amer M Zeidan, Amy E Dezern, Rami Komrokji, Mikkael A Sekeres, Bart Scott, Rena Buckstein, Sara Tinsley-Vance, Amit Verma, Tanya Wroblewski, Steven Pavletic, Kelly Norsworthy

Faculty, Staff and Student Publications

Myelodysplastic syndromes/neoplasms (MDSs) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the US Food and Drug Administration, (eg, luspatercept, ivosidenib, decitabine/cedazuridine, and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories, including criteria for risk stratification and eligibility, response definitions, time-to-event end points, transfusion end points, functional assessments, and biomarker development. Strategies to address these challenges …

Avasimibe Abolishes The Efficacy Of Fluvastatin For The Prevention Of Cancer In A Spontaneous Mouse Model Of Breast Cancer, Anjana Bhardwaj, Alexander Koh, Rhea Bhala, Janvi Sandhu, Zhenlin Ju, Leslie Faye Cando, Jing Wang, Isabelle Bedrosian

Faculty, Staff and Student Publications

The cholesterol biosynthesis pathway is upregulated during breast cancer development and progression. Inhibition of the aberrantly upregulated cholesterol pathway by statins reduces breast tumor incidence and burden by 50% in SV40 C3(1) TAg mice, a mouse model of triple negative breast cancer. We hypothesized that fluvastatin's preventive efficacy could be further enhanced by co-targeting the statin-induced restorative feedback pathways that tightly control the cholesterol pathway and are involved in resistance to statins. Acyl-coenzyme A: cholesterol acyltransferase (

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …

Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K Waller, John E Levine, John J Strouse, Joseph H Antin, Suhag H Parikh, Nitya Bakshi, Carlton Dampier, Jennifer J Jaroscak, Shayla Bergmann, Trisha Wong, Vamsi Kota, Betty Pace, Lazaros J Lekakis, Premal Lulla, Robert S Nickel, Kimberly A Kasow, Uday Popat, Wally Smith, Lolie Yu, Nancy Difronzo, Nancy Geller, Naynesh Kamani, Elizabeth S Klings, Kathryn Hassell, Adam Mendizabal, Keith Sullivan, Donna Neuberg, Lakshmanan Krishnamurti

Faculty, Staff and Students Publications

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality …

Molecular Identification Of The Italian Soldiers Found In The Second World War Mass Grave Of Ossero, Barbara Di Stefano, Barbara Bertoglio, Filomena Melchionda, Monica Concato, Solange Sorçaburu Ciglieri, Alessandro Bosetti, Pierangela Grignani, Eros Azzalini, Yasmine Addoum, Raffaella Vetrini, Fabiano Gentile, Francesco Introna, Serena Bonin, Chiara Turchi, Carlo Previderè, Paolo Fattorini

Faculty, Staff and Students Publications

Background/objectives: DNA analysis is the most reliable method for the identification of human skeletal remains, especially the ones found in mass disasters or recovered from mass graves. To this aim, DNA was extracted from bones and teeth allegedly belonging to 27 Italian soldiers executed during the Second World War and exhumed from a mass grave in Ossero (Croatia).

Methods: A selection of 131 different bone samples (petrous bones, femurs, metacarpal, and metatarsal bones) and 16 molar teeth were used for DNA extraction. Autosomal and Y-chromosome STR profiles were determined using a conventional CE approach, while a panel of 76 microhaplotypes …