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A Conditional Strategy For Cell-Type-Specific Labeling Of Endogenous Excitatory Synapses In Drosophila, Michael J. Parisi, Michael A. Aimino, Timothy J. Mosca May 2023

A Conditional Strategy For Cell-Type-Specific Labeling Of Endogenous Excitatory Synapses In Drosophila, Michael J. Parisi, Michael A. Aimino, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Chemical neurotransmission occurs at specialized contacts where neurotransmitter release machinery apposes neurotransmitter receptors to underlie circuit function. A series of complex events underlies preand postsynaptic protein recruitment to neuronal connections. To better study synaptic development in individual neurons, we need cell-type-specific strategies to visualize endogenous synaptic proteins. Although presynaptic strategies exist, postsynaptic proteins remain less studied because of a paucity of cell-type-specific reagents. To study excitatory postsynapses with cell-type specificity, we engineered dlg1[4K], a conditionally labeled marker of Drosophila excitatory postsynaptic densities. With binary expression systems, dlg1[4K] labels central and peripheral postsynapses in larvae and adults. Using dlg1[4K], we find …


Contributions To Auditory System Conduction Velocity: Insights With Multi-Modal Neuroimaging And Machine Learning In Children With Asd And Xyy Syndrome, Jeffrey I. Berman, Luke Bloy, Lisa Blaskey, Carissa R. Jackel, Judith S. Miller, Judith Ross, J. Christopher Edgar, Thimothy P.L. Roberts May 2023

Contributions To Auditory System Conduction Velocity: Insights With Multi-Modal Neuroimaging And Machine Learning In Children With Asd And Xyy Syndrome, Jeffrey I. Berman, Luke Bloy, Lisa Blaskey, Carissa R. Jackel, Judith S. Miller, Judith Ross, J. Christopher Edgar, Thimothy P.L. Roberts

Department of Pediatrics Faculty Papers

Introduction: The M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed).

Methods: The goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome.

Results: Non-linear TD …


Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh May 2023

Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

No abstract provided.


Maintenance Of Chronicity Signatures In Fibroblasts Isolated From Recessive Dystrophic Epidermolysis Bullosa Chronic Wound Dressings Under Culture Conditions, Cristian De Gregorio, Evelyng Catalán, Gabriel Garrido, Pilar Morandé, Jimena Castillo Bennett, Catalina Muñoz, Glenda Cofré, Ya-Lin Huang, Bárbara Cuadra, Paola Murgas, Margarita Calvo, Fernando Altermatt, María Joao Yubero, Francis Palisson, Andrew P. South, Marcelo Ezquer, Ignacia Fuentes May 2023

Maintenance Of Chronicity Signatures In Fibroblasts Isolated From Recessive Dystrophic Epidermolysis Bullosa Chronic Wound Dressings Under Culture Conditions, Cristian De Gregorio, Evelyng Catalán, Gabriel Garrido, Pilar Morandé, Jimena Castillo Bennett, Catalina Muñoz, Glenda Cofré, Ya-Lin Huang, Bárbara Cuadra, Paola Murgas, Margarita Calvo, Fernando Altermatt, María Joao Yubero, Francis Palisson, Andrew P. South, Marcelo Ezquer, Ignacia Fuentes

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients.

RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, …


Mechanisms Underlying The Antiarrhythmic Effect Of Arumenamide-787 In Experimental Models Of The J Wave Syndromes And Hypothermia, José M. Di Diego, Hector Barajas-Martinez, Robert Cox, Victoria M Robinson, Joseph Jung, Mohamed Fouda, Mena Abdelsayed, Peter C Ruben, Charles Antzelevitch May 2023

Mechanisms Underlying The Antiarrhythmic Effect Of Arumenamide-787 In Experimental Models Of The J Wave Syndromes And Hypothermia, José M. Di Diego, Hector Barajas-Martinez, Robert Cox, Victoria M Robinson, Joseph Jung, Mohamed Fouda, Mena Abdelsayed, Peter C Ruben, Charles Antzelevitch

Department of Medicine Faculty Papers

BACKGROUND: Brugada (BrS) and early repolarization syndromes (ERS), the so-called J wave syndromes (JWS), are associated with life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently limited. In this study, we examine the effects of ARumenamide-787 (AR-787) to suppress the electrocardiographic and arrhythmic manifestations of JWS and hypothermia.

METHODS: We studied the effects of AR-787 on INa and IKr in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (NaV1.5) sodium channel and hERG channel, respectively. In addition, we studied its effect on Ito, INa and ICa in dissociated canine ventricular myocytes along with action potentials and ECG …


When Images Don’T Explain Reality: A Case Of An Intravascular Extension Of An Endometrial Tumor, Kyle Marrache, Hussam Al Hennawi, Shayan Qadir, Angad Bedi, Kevin Ye Hou May 2023

When Images Don’T Explain Reality: A Case Of An Intravascular Extension Of An Endometrial Tumor, Kyle Marrache, Hussam Al Hennawi, Shayan Qadir, Angad Bedi, Kevin Ye Hou

Abington Jefferson Health Papers

Endometrial stromal sarcoma is a rare mesenchymal tumor with the potential for intravascular metastases. We present the case of a 52-year-old female patient with a history of previously resected endometrial sarcoma who was found to have an inferior vena cava thrombus with intracardiac extension. Pathological assessment following resection revealed intravascular extension of an underlying endometrial stromal sarcoma. This case demonstrates the aggressive nature and intracardiac metastatic potential of endometrial sarcomas.


Delayed Presentation Of Biopsy-Proven Eosinophilic Myocarditis Following Covid-19 Mrna Vaccine, Chaitra Janga, Tirth Patel, Hussam Al Hennawi, Sarin Atam, Shreeja Shah Shah, Ifrah Naeem, Rahat Memon, Donald C. Haas May 2023

Delayed Presentation Of Biopsy-Proven Eosinophilic Myocarditis Following Covid-19 Mrna Vaccine, Chaitra Janga, Tirth Patel, Hussam Al Hennawi, Sarin Atam, Shreeja Shah Shah, Ifrah Naeem, Rahat Memon, Donald C. Haas

Abington Jefferson Health Papers

Myopericarditis associated with COVID-19 mRNA vaccines has been recognized as an uncommon adverse reaction, especially among young, healthy adult males. Eosinophilic myocarditis is a rare form of inflammation reflecting a hypersensitivity reaction following an inciting event commonly caused by drugs including vaccines. Eosinophilic myocarditis, a subtype of myocarditis, is characterized by eosinophilic myocardial infiltrates. It is usually accompanied by systemic eosinophilia in the form of a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and is rarely associated with myocyte fibrosis and/or necrosis. In this report, we present a case of biopsy-proven eosinophilic myocarditis in a 24-year-old male patient, …


Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Rina Li Welkie, Pallawi Torka, Geoffrey Shouse, Reem Karmali, Lauren Shea, Andrea Anampa-Guzmán, Timothy S Oh, Heather Reaves, Montreh Tavakkoli, Kathryn Lindsey, Irl Brian Greenwell, Emily Hansinger, Colin Thomas, Sayan Mullick Chowdhury, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Nancy L Bartlett, Alex F Herrera, Natalie S Grover, Adam J Olszewski May 2023

Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Rina Li Welkie, Pallawi Torka, Geoffrey Shouse, Reem Karmali, Lauren Shea, Andrea Anampa-Guzmán, Timothy S Oh, Heather Reaves, Montreh Tavakkoli, Kathryn Lindsey, Irl Brian Greenwell, Emily Hansinger, Colin Thomas, Sayan Mullick Chowdhury, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Nancy L Bartlett, Alex F Herrera, Natalie S Grover, Adam J Olszewski

Department of Medicine Faculty Papers

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of …


Multiple And Consecutive Genome Editing Using I-Gonad And Breeding Enrichment Facilitates The Production Of Genetically Modified Mice, Carolina R Melo-Silva, Cory J Knudson, Lingjuan Tang, Samita Kafle, Lauren E. Springer, Jihae Choi, Christopher M. Snyder, Yajing Wang, Sangwon V. Kim, Luis J. Sigal May 2023

Multiple And Consecutive Genome Editing Using I-Gonad And Breeding Enrichment Facilitates The Production Of Genetically Modified Mice, Carolina R Melo-Silva, Cory J Knudson, Lingjuan Tang, Samita Kafle, Lauren E. Springer, Jihae Choi, Christopher M. Snyder, Yajing Wang, Sangwon V. Kim, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Genetically modified (GM) mice are essential tools in biomedical research. Traditional methods for generating GM mice are expensive and require specialized personnel and equipment. The use of clustered regularly interspaced short palindromic repeats (CRISPR) coupled with improved-Genome editing via Oviductal Nucleic Acids Delivery (i-GONAD) has highly increased the feasibility of producing GM mice in research laboratories. However, genetic modification in inbred mouse strains of interest such as C57BL/6 (B6) is still challenging because of their low fertility and embryo fragility. We have successfully generated multiple novel GM mouse strains in the B6 background while attempting to optimize i-GONAD. We found …


Impact Of The Covid-19 Pandemic On The Management Of Risk Factors In Patients With Stable Atherosclerotic Vascular Disease, Dean Karalis, Patrick Moeller, Albert Crawford, Maria Janelli, Scott Hessen May 2023

Impact Of The Covid-19 Pandemic On The Management Of Risk Factors In Patients With Stable Atherosclerotic Vascular Disease, Dean Karalis, Patrick Moeller, Albert Crawford, Maria Janelli, Scott Hessen

Division of Cardiology Faculty Papers

Background

Effective control of risk factors in patients with ASCVD is important to reduce recurrent cardiovascular events. However, many ASCVD patients do not have their risk factors controlled, and this may have worsened during the COVID-19 pandemic.

Methods

We retrospectively evaluated risk factor control among 24,760 ASCVD patients who had at least 1 outpatient encounter both pre-pandemic and during the first year of the pandemic. Risk factors were uncontrolled if the blood pressure (BP) ≥ 130/80 mm Hg, LDL-C ≥ 70 mg/dL, HgbA1c ≥ 7 for diabetic patients, and patients were current smokers.

Results

During the pandemic, many patients had …


The End Of Roe V. Wade: Implications For Women's Mental Health And Care, Amalia Londoño Tobón, Eileen Mcnicholas, Camille A Clare, Luu D Ireland, Jennifer L Payne, Tiffany A Moore Simas, Rachel K Scott, Madeleine Becker, Nancy Byatt May 2023

The End Of Roe V. Wade: Implications For Women's Mental Health And Care, Amalia Londoño Tobón, Eileen Mcnicholas, Camille A Clare, Luu D Ireland, Jennifer L Payne, Tiffany A Moore Simas, Rachel K Scott, Madeleine Becker, Nancy Byatt

Marcus Institute of Integrative Health Faculty Papers

The Supreme Court decision in Dobbs v. Jackson in June 2022 reversed precedent which had previously protected abortion prior to fetal viability as a universal right within the United States. This decision almost immediately led to abortion restrictions across 25 states. The resulting lack of access to abortion care for millions of pregnant people will have profound physical and mental health consequences, the full effects of which will not be realized for years to come. Approximately 1 in 5 women access abortions in the U.S. each year. These women are diverse and represent all American groups. The Supreme court decision, …


Gold 2023 Update: Implications For Clinical Practice, Diana R. Tamondong-Lachica, Neil Skolnik, John R. Hurst, Nathaniel Marchetti, Adrian Paul J. Rabe, Maria Montes De Oca, Bartolome R. Celli May 2023

Gold 2023 Update: Implications For Clinical Practice, Diana R. Tamondong-Lachica, Neil Skolnik, John R. Hurst, Nathaniel Marchetti, Adrian Paul J. Rabe, Maria Montes De Oca, Bartolome R. Celli

Abington Jefferson Health Papers

In 2022, over 3 million people died of chronic obstructive pulmonary disease (COPD) and the global burden of the disease is expected to increase over the coming decades. Recommendations for the treatment and management of patients with COPD are published by the Global Initiative for Chronic Obstructive Lung Disease, and updated annually with scientific evidence-based recommendations. The 2023 updates, published in November 2022, contain key changes to recommendations for diagnosis and treatment of COPD that are anticipated to have a significant impact on clinical practice for patients with COPD. Updates to how COPD is defined and diagnosed, including the expansion …


Species Differences In Platelet Protease-Activated Receptors, Stephanie A Renna, Steven E. Mckenzie, James V. Michael May 2023

Species Differences In Platelet Protease-Activated Receptors, Stephanie A Renna, Steven E. Mckenzie, James V. Michael

Cardeza Foundation for Hematologic Research

Protease-activated receptors (PARs) are a class of integral membrane proteins that are cleaved by a variety of proteases, most notably thrombin, to reveal a tethered ligand and promote activation. PARs are critical mediators of platelet function in hemostasis and thrombosis, and therefore are attractive targets for anti-platelet therapies. Animal models studying platelet PAR physiology have relied heavily on genetically modified mouse strains, which have provided ample insight but have some inherent limitations. The current review aims to summarize the notable PAR expression and functional differences between the mouse and human, in addition to highlighting some recently developed tools to further …


Neurodevelopment, Vision And Auditory Outcomes At Age 2 Years In Offspring Of Participants In The ‘Women First’ Maternal Preconception Nutrition Randomised Controlled Trial, Michelle Fernandes, Nancy F. Krebs, Jamie Westcott, Antoinette Tshefu, Adrien Lokangaka, Melissa Bauserman, Ana L. Garcés, Lester Figueroa, Sarah Saleem, Sumera A. Aziz, Robert L. Goldenberg, Shivaprasad S. Goudar, Sangappa M. Dhaded, Richard J. Derman, Jennifer F. Kemp, Marion Koso-Thomas, Amaanti Sridhar, Elizabeth M. Mcclure, K. Michael Hambidge May 2023

Neurodevelopment, Vision And Auditory Outcomes At Age 2 Years In Offspring Of Participants In The ‘Women First’ Maternal Preconception Nutrition Randomised Controlled Trial, Michelle Fernandes, Nancy F. Krebs, Jamie Westcott, Antoinette Tshefu, Adrien Lokangaka, Melissa Bauserman, Ana L. Garcés, Lester Figueroa, Sarah Saleem, Sumera A. Aziz, Robert L. Goldenberg, Shivaprasad S. Goudar, Sangappa M. Dhaded, Richard J. Derman, Jennifer F. Kemp, Marion Koso-Thomas, Amaanti Sridhar, Elizabeth M. Mcclure, K. Michael Hambidge

Global Health Articles

BACKGROUND: Maternal nutrition in preconception and early pregnancy influences fetal growth. Evidence for effects of prenatal maternal nutrition on early child development (ECD) in low-income and middle-income countries is limited.

OBJECTIVES: To examine impact of maternal nutrition supplementation initiated prior to or during pregnancy on ECD, and to examine potential association of postnatal growth with ECD domains.

DESIGN: Secondary analysis regarding the offspring of participants of a maternal multicountry, individually randomised trial.

SETTING: Rural Democratic Republic of the Congo, Guatemala, India and Pakistan.

PARTICIPANTS: 667 offspring of Women First trial participants, aged 24 months.

INTERVENTION: Maternal lipid-based nutrient supplement initiated …


Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev May 2023

Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca2+ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca2+] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca2+ accumulation, thereby reducing ROS production and stress-induced intracellular Ca2+ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca2+] in female rat VCMs challenged …


Bibliometric Analysis Of Academic Journal Recommendations And Requirements For Surgical And Anesthesiologic Adverse Events Reporting, Tamir N. Sholklapper, Jorge Ballon, Aref S. Sayegh, Anibal La Riva, Laura C. Perez, Sherry Huang, Michael Eppler, Gregg Nelson, Giovanni Marchegiani, Robert Hinchliffe, Luca Gordini, Marc Furrer, Michael J. Brenner, Salome Dell-Kuster, Chandra Shekhar Biyani, Nader Francis, Haytham M.A. Kaafarani, Matthias Siepe, Des Winter, Julie A. Sosa, Francesco Bandello, Robert Siemens, Jochen Walz, Alberto Briganti, Christian Gratzke, Andre L. Abreu, Mihir M. Desai, Rene Sotelo, Riaz Agha, Keith D. Lillemoe, Steven Wexner, Gary S. Collins, Inderbir Gill, Giovanni E. Cacciamani May 2023

Bibliometric Analysis Of Academic Journal Recommendations And Requirements For Surgical And Anesthesiologic Adverse Events Reporting, Tamir N. Sholklapper, Jorge Ballon, Aref S. Sayegh, Anibal La Riva, Laura C. Perez, Sherry Huang, Michael Eppler, Gregg Nelson, Giovanni Marchegiani, Robert Hinchliffe, Luca Gordini, Marc Furrer, Michael J. Brenner, Salome Dell-Kuster, Chandra Shekhar Biyani, Nader Francis, Haytham M.A. Kaafarani, Matthias Siepe, Des Winter, Julie A. Sosa, Francesco Bandello, Robert Siemens, Jochen Walz, Alberto Briganti, Christian Gratzke, Andre L. Abreu, Mihir M. Desai, Rene Sotelo, Riaz Agha, Keith D. Lillemoe, Steven Wexner, Gary S. Collins, Inderbir Gill, Giovanni E. Cacciamani

Einstein Health Papers

BACKGROUND: Standards for reporting surgical adverse events (AEs) vary widely within the scientific literature. Failure to adequately capture AEs hinders efforts to measure the safety of healthcare delivery and improve the quality of care. The aim of the present study is to assess the prevalence and typology of perioperative AE reporting guidelines among surgery and anesthesiology journals.

MATERIALS AND METHODS: In November 2021, three independent reviewers queried journal lists from the SCImago Journal & Country Rank (SJR) portal (www.scimagojr.com), a bibliometric indicator database for surgery and anesthesiology academic journals. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted …


Rerupture Outcome Of Conservative Versus Open Repair Versus Minimally Invasive Repair Of Acute Achilles Tendon Ruptures: A Systematic Review And Meta-Analysis, Haidong Deng, Xin Cheng, Yi Yang, Fang Fang, Jialing He, Yixin Tian, Tiangui Li, Yangchun Xiao, Yuning Feng, Peng Wang, Weelic Chong, Yang Hai, Yu Zhang May 2023

Rerupture Outcome Of Conservative Versus Open Repair Versus Minimally Invasive Repair Of Acute Achilles Tendon Ruptures: A Systematic Review And Meta-Analysis, Haidong Deng, Xin Cheng, Yi Yang, Fang Fang, Jialing He, Yixin Tian, Tiangui Li, Yangchun Xiao, Yuning Feng, Peng Wang, Weelic Chong, Yang Hai, Yu Zhang

Department of Medicine Faculty Papers

OBJECTIVE: To compare the rerupture rate after conservative treatment, open repair, and minimally invasive surgery management of acute Achilles tendon ruptures.

DESIGN: Systematic review and network meta-analysis.

DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 2022.

METHODS: Randomised controlled trials involving different treatments for Achilles tendon rupture were included. The primary outcome was rerupture. Bayesian network meta-analysis with random effects was used to assess pooled relative risks (RRs) and 95% confidence intervals. We evaluated the heterogeneity and publication bias.

RESULTS: Thirteen trials with 1465 patients were included. In direct comparison, …


Parkin Ubiquitination Of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression, Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M Cecilia Caino, Dario C. Altieri May 2023

Parkin Ubiquitination Of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression, Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M Cecilia Caino, Dario C. Altieri

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Mitochondria are signaling organelles implicated in cancer, but the mechanisms are elusive. Here, we show that Parkin, an E3 ubiquitination (Ub) ligase altered in Parkinson's disease, forms a complex with the regulator of cell motility, Kindlin-2 (K2), at mitochondria of tumor cells. In turn, Parkin ubiquitinates Lys581 and Lys582 using Lys48 linkages, resulting in proteasomal degradation of K2 and shortened half-life from ∼5 h to ∼1.5 h. Loss of K2 inhibits focal adhesion turnover and β1 integrin activation, impairs membrane lamellipodia size and frequency, and inhibits mitochondrial dynamics, altogether suppressing tumor cell-extracellular matrix interactions, migration, and invasion. Conversely, Parkin does …


Inpatient Opioid Use Varies By Construct Length Among Laminoplasty Versus Laminectomy And Fusion Patients, Harry M. Lightsey, Peter J. Georgakas, Matthew H. Lindsey, Caleb M. Yeung, Joseph H. Schwab, Harold A. Fogel, Stuart H. Hershman, Daniel G. Tobert, Kevin M. Hwang May 2023

Inpatient Opioid Use Varies By Construct Length Among Laminoplasty Versus Laminectomy And Fusion Patients, Harry M. Lightsey, Peter J. Georgakas, Matthew H. Lindsey, Caleb M. Yeung, Joseph H. Schwab, Harold A. Fogel, Stuart H. Hershman, Daniel G. Tobert, Kevin M. Hwang

Rothman Institute Papers

BACKGROUND: Laminoplasty (LP) and laminectomy and fusion (LF) are utilized to achieve decompression in patients with symptomatic degenerative cervical myelopathy (DCM). Comparative analyses aimed at determining outcomes and clarifying indications between these procedures represent an area of active research. Accordingly, we sought to compare inpatient opioid use between LP and LF patients and to determine if opioid use correlated with length of stay.

METHODS: Sociodemographic information, surgical and hospitalization data, and medication administration records were abstracted for patients >18 years of age who underwent LP or LF for DCM in the Mass General Brigham (MGB) health system between 2017 and …


Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival Of Patients With Recurrent Glioblastoma In A Randomized Trial, Tulika Ranjan, Soma Sengupta, Michael J. Glantz, Richard M. Green, Alexander Yu, Dawit Aregawi, Rekha Chaudhary, Ricky Chen, Mario Zuccarello, Christine Lu-Emerson, Hugh D. Moulding, Neil Belman, Jon Glass, Aaron Mammoser, Mark Anderson, Jagan Valluri, Nicholas Marko, Jason Schroeder, Steven Jubelirer, Frances Chow, Pier Paolo Claudio, Anthony M. Alberico, Seth T. Lirette, Krista L. Denning, Candace M. Howard May 2023

Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival Of Patients With Recurrent Glioblastoma In A Randomized Trial, Tulika Ranjan, Soma Sengupta, Michael J. Glantz, Richard M. Green, Alexander Yu, Dawit Aregawi, Rekha Chaudhary, Ricky Chen, Mario Zuccarello, Christine Lu-Emerson, Hugh D. Moulding, Neil Belman, Jon Glass, Aaron Mammoser, Mark Anderson, Jagan Valluri, Nicholas Marko, Jason Schroeder, Steven Jubelirer, Frances Chow, Pier Paolo Claudio, Anthony M. Alberico, Seth T. Lirette, Krista L. Denning, Candace M. Howard

Department of Neurosurgery Faculty Papers

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors.

In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = …


Contemporary Homozygous Familial Hypercholesterolemia In The United States: Insights From The Cascade Fh Registry, Marina Cuchel, Paul C. Lee, Lisa C. Hudgins, P. Barton Duell, Zahid Ahmad, Seth J. Baum, Macrae F. Linton, Sarah D. De Ferranti, Christie M. Ballantyne, John A. Larry, Linda C. Hemphill, Iris Kindt, Samuel S. Gidding, Seth S. Martin, Patrick M. Moriarty, Paul P. Thompson, James A. Underberg, John R. Guyton, Rolf L. Andersen, David J. Whellan, Irwin Benuck, John P. Kane, Kelly Myers, William Howard, David Staszak, Allison Jamison, Mary C. Card, Mafalda Bourbon, Joana R. Chora, Daniel J. Rader, Joshua W. Knowles, Katherine Wilemon, Mary P. Mcgowan May 2023

Contemporary Homozygous Familial Hypercholesterolemia In The United States: Insights From The Cascade Fh Registry, Marina Cuchel, Paul C. Lee, Lisa C. Hudgins, P. Barton Duell, Zahid Ahmad, Seth J. Baum, Macrae F. Linton, Sarah D. De Ferranti, Christie M. Ballantyne, John A. Larry, Linda C. Hemphill, Iris Kindt, Samuel S. Gidding, Seth S. Martin, Patrick M. Moriarty, Paul P. Thompson, James A. Underberg, John R. Guyton, Rolf L. Andersen, David J. Whellan, Irwin Benuck, John P. Kane, Kelly Myers, William Howard, David Staszak, Allison Jamison, Mary C. Card, Mafalda Bourbon, Joana R. Chora, Daniel J. Rader, Joshua W. Knowles, Katherine Wilemon, Mary P. Mcgowan

Division of Cardiology Faculty Papers

Background

Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment‐resistant disorder characterized by early‐onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain.

Methods and Results

Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the …


Removing Barriers To Tecovirimat For Mpox-Infected Individuals Via Novel Models Of Care Delivery, Michael Mccarthy, Ba, Joe Glowacki, Do, Ms, Rostislav Livinsky, Pa, Daniel Taupin, Md, Mhqs, Dagan Coppock, Md. Msce May 2023

Removing Barriers To Tecovirimat For Mpox-Infected Individuals Via Novel Models Of Care Delivery, Michael Mccarthy, Ba, Joe Glowacki, Do, Ms, Rostislav Livinsky, Pa, Daniel Taupin, Md, Mhqs, Dagan Coppock, Md. Msce

Division of Infectious Diseases and Environmental Medicine Posters

Problem Statement

During the 2022 mpox outbreak, the CDC’s expanded access Investigational New Drug (IND) protocol created a practical barrier to the outpatient provision of tecovirimat. We rapidly implemented a tecovirimat prescription program for individuals infected with mpox to improves access to care.

Project AIM

Primary aim: describe how we rapidly implemented a program for increasing tecovirimat distribution in a metropolitan area.

Secondary aims: describe the patient population who received tecovirimat as treatment for mpox at our clinic and analyze several clinically relevant time intervals along the continuum of care delivery.


A Word From The Writing Team (May 2023), Pam Walter, Mfa, Liz Declan, Ma, Mfa May 2023

A Word From The Writing Team (May 2023), Pam Walter, Mfa, Liz Declan, Ma, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

  • Join us for our First Friday writing retreat of the semester!
  • Faculty Days 2023
  • Publication Spotlight
  • Reminders


Micu1 Occludes The Mitochondrial Calcium Uniporter In Divalent-Free Conditions, Macarena Rodríguez-Prados, Elena Berezhnaya, Maria Teresa Castromonte, Sergio L. Menezes-Filho, Melanie Paillard, György Hajnóczky May 2023

Micu1 Occludes The Mitochondrial Calcium Uniporter In Divalent-Free Conditions, Macarena Rodríguez-Prados, Elena Berezhnaya, Maria Teresa Castromonte, Sergio L. Menezes-Filho, Melanie Paillard, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial Ca2+ uptake is mediated by the mitochondrial uniporter complex (mtCU) that includes a tetramer of the pore-forming subunit, MCU, a scaffold protein, EMRE, and the EF-hand regulatory subunit, MICU1 either homodimerized or heterodimerized with MICU2/3. MICU1 has been proposed to regulate Ca2+ uptake via the mtCU by physically occluding the pore and preventing Ca2+ flux at resting cytoplasmic [Ca2+] (free calcium concentration) and to increase Ca2+ flux at high [Ca2+] due to cooperative activation of MICUs EF-hands. However, mtCU and MICU1 functioning when its EF-hands are unoccupied by Ca2+ is poorly studied due to technical limitations. To overcome this …


Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas May 2023

Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas

Department of Neurology Faculty Papers

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the …


Diagnosis Of Oral Cancers By Targeting Vpac Receptors: Preliminary Report, Rajendra Nerli, Mahesh Kalloli, Shadab Rangrez, Shridhar C Ghagane, Kumar Vinchurkar, Shreya Chandra, Mathew L. Thakur May 2023

Diagnosis Of Oral Cancers By Targeting Vpac Receptors: Preliminary Report, Rajendra Nerli, Mahesh Kalloli, Shadab Rangrez, Shridhar C Ghagane, Kumar Vinchurkar, Shreya Chandra, Mathew L. Thakur

Department of Radiology Faculty Papers

Introduction: Oral cancer is a major health problem. The study of exfoliative cytology material helps in the differentiation of premalignant and malignant alterations of oral lesions. The objective of this study was to assess the feasibility of detecting oral cancer by targeting genomic VPAC (combined vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide) receptors expressed on malignant oral cancer cells.

Patients & methods: All patients with suspected oral cavity cancers/lesions formed the study group. The samples from the oral cavity lesion or suspicious area were collected with a cytology brush. The harvested material was examined for malignant cells by …


Hemiplegic Shoulder Pain Prevention: A Collaborative Approach With Nursing And Occupational Therapy In Acute Care, Ebonee V. Cole, Ms, Otr/L, Cbis Apr 2023

Hemiplegic Shoulder Pain Prevention: A Collaborative Approach With Nursing And Occupational Therapy In Acute Care, Ebonee V. Cole, Ms, Otr/L, Cbis

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Introduction: Hemiplegic shoulder pain (HSP) is one of the most common and disabling complications of arm hemiplegia after stroke (Anwer & Alghadir, 2020), with a prevalence as high as 75% of strokes (Xie et al., 2021). HSP can develop as early as the second week (Praveen Raj et al., 2021), may continue several months after stroke in 65% of patients (Kumar, 2019), and is associated with reduced functional arm use (Kumar, 2019). Prevention is the ideal management strategy of HSP (K. Walsh, 2001). Implementing hemiplegic arm management techniques, such as positioning and handling, is key to preventing HSP. In the …


Publication Rates Of Abstracts Presented Across 6 Major Spine Specialty Conferences, Tariq Z. Issa, Yunsoo Lee, Mark J. Lambrechts, Christopher Reynolds, Ryan Cha, James Kim, Jose A. Canseco, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder, Alan S. Hilibrand Apr 2023

Publication Rates Of Abstracts Presented Across 6 Major Spine Specialty Conferences, Tariq Z. Issa, Yunsoo Lee, Mark J. Lambrechts, Christopher Reynolds, Ryan Cha, James Kim, Jose A. Canseco, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder, Alan S. Hilibrand

Rothman Institute Papers

Background: Although scientific researchers aim to present their projects at academic conferences as a step toward publication, not all projects mature to become a peer-reviewed manuscript. The publication rate of meetings can be utilized to assess the quality of presented research. Our objective was to evaluate the contemporary publication rate of abstracts presented at spine conferences.

Methods: We reviewed annual meeting programs of North American Spine Society (NASS), Scoliosis Research Society (SRS), International Meeting on Advanced Spine Techniques (IMAST), Spine Global Spine Congress (GSC), Lumbar Spine Research Society (LSRS), and Cervical Spine Research Society (CSRS) from 2017 to 2019. Abstracts …


Does Prehabilitation Before Surgery Affect Return To Sport In Baseball Pitchers With Partial Ulnar Collateral Ligament Tears?, Kourtney Snigar, Ryan W. Paul, Joshua M. Spada, Usman Zareef, Anya Hall, Brandon J. Erickson, Michael G. Ciccotti, Stephen J. Thomas Apr 2023

Does Prehabilitation Before Surgery Affect Return To Sport In Baseball Pitchers With Partial Ulnar Collateral Ligament Tears?, Kourtney Snigar, Ryan W. Paul, Joshua M. Spada, Usman Zareef, Anya Hall, Brandon J. Erickson, Michael G. Ciccotti, Stephen J. Thomas

Rothman Institute Papers

BACKGROUND: Purposeful rehabilitation before surgery (prehabilitation) has been researched and implemented in the treatment of anterior cruciate ligament tears. However, it is unclear whether prehabilitation would affect outcomes for baseball pitchers with partial ulnar collateral ligament (UCL) tears.

PURPOSE/HYPOTHESIS: The purpose of this study was to determine whether baseball pitchers with partial UCL tears who completed ≥4 weeks of prehabilitation (prehab group) have different return to play (RTP) outcomes than pitchers with 0 to 3 weeks of preoperative physical therapy (no prehab group). We hypothesized that pitchers in the prehab group would have similar RTP rates compared with pitchers in …


A Systematic Review Identifying Adverse Health Outcomes And Mortality Rates Associated With Telehealth, Fidelia Cascini, Ana Pantovic, Yazan A. Al-Ajlouni, Omar Al Ta'ani, Giovanna Failla, Andriy Melnyk, Paul Barach, Walter Ricciardi Apr 2023

A Systematic Review Identifying Adverse Health Outcomes And Mortality Rates Associated With Telehealth, Fidelia Cascini, Ana Pantovic, Yazan A. Al-Ajlouni, Omar Al Ta'ani, Giovanna Failla, Andriy Melnyk, Paul Barach, Walter Ricciardi

College of Population Health Faculty Papers

Background: The literature supporting telehealth management is growing accelerated by the COVID-pandemic. We hypothesize that there are risks of adverse events associated with telehealth interventions.

Methods: A review of PubMed (including MEDLINE), Embase, ISI (Web of Science), VHL/GHL, Scopus, Science Direct, and PsycINFO was conducted for all adverse events associated with telehealth from January 1, 1960 to March 1, 2021. This systematic review and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Of 5,144 citations 78 published studies met criteria for quality evaluation and underwent full text abstraction including the qualitative …