Medicine and Health Sciences Commons^™

Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar A. Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel

Internal Medicine Publications

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not …

Inhibition Of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (Mptp) Opening In Ischemia-Damaged Mitochondria, Qun Chen, Haishan Xu, Aijun Xu, Thomas Ross, Elizabeth Bowler, Ying Hu, Edward J. Lesnefsky

Internal Medicine Publications

Background

Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome crelease and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes.

Methods

Calcium retention capacity …

Correlation Between Mass And Volume Of Collected Blood With Positivity Of Blood Cultures, Lariessa Neves, Alexandre Rodrigues Marra, Thiago Zinsly Sampaio Camargo, Maura Cristina Dos Santos, Flávia Zulin, Patrícia Candido Da Silva, Natália Ariede De Moura, Elivane Da Silva Victor, Jacyr Pasternak, Oscar Fernando Pavão Dos Santos, Michael B. Edmond, Marines Dalla Valle Martino

Internal Medicine Publications

Background

The collection of blood cultures is an extremely important method in the management of patients with suspected infection. Microbiology laboratories should monitor blood culture collection.

Methods

Over an 8-month period we developed a prospective, observational study in an adult Intensive Care Unit (ICU). We correlated the mass contained in the blood vials with blood culture positivity and we also verified the relationship between the mass of blood and blood volume collected for the diagnosis of bloodstream infection (BSI), as well as we explored factors predicting positive blood cultures.

Results

We evaluated 345 patients with sepsis, severe sepsis or septic …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

An International Survey On Taking Up A Career In Cardiovascular Research: Opportunities And Biases Toward Would-Be Physician-Scientists, Giuseppe Biondi-Zoccai, Enrico Cerrato, Mariangela Peruzzi, Fabrizio D'Ascenzo, Elena De Falco, Isotta Chimenti, Sebastiano Sciarretta, Antonio G. M. Marullo, Elena Cavarretta, Ernesto Greco, Umberto Benedetto, Giulio Pompilio, Javier Escaned, Antonio Abbate, Alain Carpentier, Juan Carlos Chachques, Giacomo Frati

Internal Medicine Publications

Background

Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey.

Methods and Results

We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, …

Early Goal-Directed Resuscitation Of Patients With Septic Shock: Current Evidence And Future Directions, Ravi G. Gupta, Sarah M. Hartigan, Markos G. Kashiouris, Curtis N. Sessler, Gonzalo M. L. Bearman

Internal Medicine Publications

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect …

Thyroid Hormone Mediated Modulation Of Energy Expenditure, Janina A. Vaitkus, Jared S. Farrar, Francesco S. Celi

Internal Medicine Publications

Thyroid hormone (TH) has diverse effects on mitochondria and energy expenditure (EE), generating great interest and research effort into understanding and harnessing these actions for the amelioration and treatment of metabolic disorders, such as obesity and diabetes. Direct effects on ATP utilization are a result of TH’s actions on metabolic cycles and increased cell membrane ion permeability. However, the majority of TH induced EE is thought to be a result of indirect effects, which, in turn, increase capacity for EE. This review discusses the direct actions of TH on EE, and places special emphasis on the indirect actions of TH, …

Non-Alcoholic Steatohepatitis: Limited Available Treatment Options But Promising Drugs In Development And Recent Progress Towards A Regulatory Approval Pathway, Claudia Filozof, Barry J. Goldstein, Richard N. Williams, Arun Sanyal

Internal Medicine Publications

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing world-wide in parallel to the increase of the obesity epidemic. Insulin resistance (IR) and the accumulation of triglyceride-derived toxic lipid metabolites play a key role in its pathogenesis. Multiple biomarkers are being evaluated for the non-invasive diagnosis of NASH. However, a percutaneous liver biopsy is still the gold standard method; the minimal diagnostic criteria include the presence of >5 % macrovesicular steatosis, inflammation, and liver cell ballooning. Several pharmaceutical agents have been evaluated for the treatment of NASH; however, no single therapy has been approved so …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Viashali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlavin, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chementi, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum …

Ascorbate-Dependent Vasopressor Synthesis: A Rationale For Vitamin C Administration In Severe Sepsis And Septic Shock?, Anitra C. Carr, Geoffrey M. Shaw, Alpha A. Fowler, Ramesh Natarajan

Internal Medicine Publications

Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical …

Intermittent Hypoxia In Childhood: The Harmful Consequences Versus Potential Benefits Of Therapeutic Uses, Tatiana V. Serebrovskaya, Lei Xi

Internal Medicine Publications

Intermittent hypoxia (IH) often occurs in early infancy in both preterm and term infants and especially at 36–44 weeks postmenstrual age. These episodes of IH could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of IH on development, behavior, academic achievement, and cognition in children with sleep apnea syndrome. It remains uncertain about the exact causative relationship between the neurocognitive and behavioral morbidities and IH and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate IH conditioning/training has been used in sick children for treating …

Use Of Probe-Based Confocal Laser Endomicroscopy (Pcle) In Gastrointestinal Applications. A Consensus Report Based On Clinical Evidence, Kenneth K. Wang, David L. Carr-Locke, Satish K. Singh, Helmut Neumann, Helga Bertani, Jean-Paul Galmiche, Razvan I. Arsenescu, Fabrice Caillol, Kenneth J. Chang, Stanislas Chaussade, Emmanuel Coron, Guida Costamagna, Aldona Dlugosz, S Ian Gan, Marc Giovannini, Frank G. Gress, Oleh Haluszka, Khek Y. Ho, Michel Kahaleh, Vani J. Konda, Frederic Prat, Raj J. Shah, Prateek Sharma, Adam Slivka, Herbert C. Wolfsen, Alvin Zfass

Internal Medicine Publications

Background

Probe-based confocal laser endomicroscopy (pCLE) provides microscopic imaging during an endoscopic procedure. Its introduction as a standard modality in gastroenterology has brought significant progress in management strategies, affecting many aspects of clinical care and requiring standardisation of practice and training.

Objective

This study aimed to provide guidance on the standardisation of its practice and training in Barrett’s oesophagus, biliary strictures, colorectal lesions and inflammatory bowel diseases.

Methods

Initial statements were developed by five group leaders, based on the available clinical evidence. These statements were then voted and edited by the 26 participants, using a modified Delphi approach. After two …

Description And Pilot Evaluation Of The Metabolic Irregularities Narrowing Down Device Software: A Case Analysis Of Physician Programming, Markos G. Kashiouris, Miloš Miljković, Vitaly Herasevich, Andrew D. Goldberg, Charles Albrecht, Iii

Internal Medicine Publications

Background: There is a gap between the abilities and the everyday applications of Computerized Decision Support Systems (CDSSs). This gap is further exacerbated by the different ‘worlds’ between the software designers and the clinician end-users. Software programmers often lack clinical experience whereas practicing physicians lack skills in design and engineering.

Objective: Our primary objective was to evaluate the performance of Metabolic Irregularities Narrowing down Device (MIND) intelligent medical calculator and differential diagnosis software through end-user surveys and discuss the roles of CDSS in the inpatient setting.

Setting: A tertiary care, teaching community hospital.

Study participants: Thirty-one …

Psychosocial Factors Of Caregiver Burden In Child Caregivers: Results From The New National Study Of Caregiving, Steven A. Cohen, Sarah Cook, Lauren Kelley, Trisha Sando, Alison E. Bell

Internal Medicine Publications

Background

Over 50 million informal caregivers in the United States provide care to an aging adult, saving the economy hundreds of billions of dollars annually from costly hospitalization or institutionalization. Despite the benefits associated with caregiving, caregiver stress can lead to negative physical and mental health consequences, or “caregiver burden”. Given these potential negative consequences of caregiver burden, it is important not only to understand the multidimensional components of burden but to also understand the experience from the perspective of the caregiver themselves. Therefore, the objectives of our study are to use exploratory factor analysis to obtain a set of …

Rational Combinations Of Targeted Agents In Aml, Prithviraj Bose, Steven Grant

Internal Medicine Publications

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex …

Determinants Of An Elevated Pulmonary Arterial Pressure In Patients With Pulmonary Arterial Hypertension, Seiichiro Sakao, Norbert F. Voelkel, Nobuhiro Tanabe, Koichiro Tatsumi

Internal Medicine Publications

Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P_pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P_pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH …

A Comprehensive Assessment Of Environmental Exposures Among 1000 North American Patients With Primary Sclerosing Cholangitis, With And Without Inflammatory Bowel Disease, J. E. Eaton, B. D. Juran, E. J. Atkinson, E. M. Schlicht, X. Xie, M. De Andrade, C. S. Lammert, V. A. Luketic, J. A. Odin, A. A. Koteish, K. V. Kowdley, K. B. Chopra, G. M. Hirschfield, N. P. Chalasani, K. N. Lazaridis

Internal Medicine Publications

Background

The relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown.

Aims

To validate associations reported in previous studies and to identify novel environmental exposures among PSC patients.

Methods

We performed a multicenter, case–control analysis utilising self-administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259).

Results

Smoking was associated with PSC only when IBD was present (OR, 0.5; …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chimenti, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median …

Inhibition Of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (Mptp) Opening In Ischemia-Damaged Mitochondria, Qun Chen, Haishan Xu, Aijun Xu, Thomas Ross, Elizabeth Bowler, Ying Hu, Edward J. Lesnefsky

Internal Medicine Publications

Background

Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome crelease and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes.

Methods

Calcium retention capacity …

Structural Mechanisms Of Dream Complex Assembly And Regulation, Keelan Z. Guiley, Tyler J. Liban, Jessica G. Felthousen, Parameshwaran Ramanan, Larisa Litovchick, Seth M. Rubin

Internal Medicine Publications

The DREAM complex represses cell cycle genes during quiescence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130. Upon cell cycle entry, MuvB dissociates from p107/p130 and recruits B-Myb and FoxM1 for up-regulating mitotic gene expression. To understand the biochemical mechanisms underpinning DREAM function and regulation, we investigated the structural basis for DREAM assembly. We identified a sequence in the MuvB component LIN52 that binds directly to the pocket domains of p107 and p130 when phosphorylated on the DYRK1A kinase site S28. A crystal structure of the LIN52–p107 complex reveals that LIN52 uses a …

Co-Administration Of The Mtorc1/Torc2 Inhibitor Ink128 And The Bcl-2/Bcl-Xl Antagonist Abt-737 Kills Human Myeloid Leukemia Cells Through Mcl-1 Down-Regulation And Akt Inactivation, Mohamed Rahmani, Mandy Mayo Aust, Elisa Hawkins, Rebecca E. Parker, Masey Ross, Maciej Kmieciak, Leonid Borisovich Reshko, Kathryn A. Rizzo, Catherine I. Dumur, Andrea Ferreira-Gonzalez, Steven Grant

Internal Medicine Publications

Effects of concurrent inhibition of mTORC1/2 and Bcl-2/Bcl-xL in human acute myeloid leukemia cells were examined. Tetracycline-inducible Bcl-2/Bcl-xL dual knockdown markedly sensitized acute myeloid leukemia cells to the dual TORC1/2 inhibitor INK128 in vitro as well as in vivo. Moreover, INK128 co-administered with the Bcl-2/xL antagonist ABT-737 sharply induced cell death in multiple acute myeloid leukemia cell lines, including TKI-resistant FLT3-ITD mutants and primary acute myeloid leukemia blasts carrying various genetic aberrations e.g., FLT3, IDH2, NPM1, and Kras, while exerting minimal toxicity toward normal hematopoietic CD34+ cells. Combined treatment was particularly active against CD34+/CD38−/CD123+ primitive leukemic progenitor …

Infrared Imaging Enhances Retinal Crystals In Bietti’S Crystalline Dystrophy, Vikram S. Brar, William H. Benson

Internal Medicine Publications

Infrared imaging dramatically increased the number of crystalline deposits visualized compared with clinical examination, standard color fundus photography, and red free imaging in patients with Bietti’s crystalline dystrophy. We believe that this imaging modality significantly improves the sensitivity with which these lesions are detected, facilitating earlier diagnosis and may potentially serve as a prognostic indicator when examined over time.

An International Survey On Taking Up A Career In Cardiovascular Research: Opportunities And Biases Toward Would-Be Physician-Scientists, Giuseppe Biondi-Zoccai, Enrico Cerrato, Mariangela Peruzzi, Fabrizio D'Ascenzo, Elena De Falco, Isotta Chimenti, Sebastiano Sciarretta, Antonino G. M. Marullo, Elena Cavarretta, Ernesto Greco, Umberto Benedetto, Giulio Pompilio, Javier Escaned, Antonio Abbate, Alain Carpentier, Juan Carlos Chachques, Giacomo Frati

Internal Medicine Publications

Background

Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey.

Methods and Results

We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

Inhibition Of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (Mptp) Opening In Ischemia-Damaged Mitochondria, Qun Chen, Haishan Xu, Aijun Xu, Thomas Ross, Elizabeth Bowler, Ying Hu, Edward J. Lesnefsky

Internal Medicine Publications

Background

Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes.

Methods

Calcium retention capacity …

Epigenetic Modifications Of The Pgc-1Α Promoter During Exercise Induced Expression In Mice, Timothy L. Lochmann, Ravindar R. Thomas, James P. Bennett, Shirley M. Taylor

Massey Comprehensive Cancer Center Publications

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not …

Role Of Interleukin-1 In Radiation-Induced Cardiomyopathy, Eleonora Mezzaroma, Ross B. Mikkelsen, Stefano Toldo, Adolfo G. Mauro, Khushboo Sharma, Carlo Marchetti, Asim Alam, Benjamin W. Van Tassell, David A. Gewirtz, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. …

Quality Control Material For The Detection Of Somatic Mutations In Fixed Clinical Specimens By Next-Generation Sequencing, Catherine I. Dumur, Jorge A. Almenara, Celeste N. Powers, Andrea Ferreira-Gonzalez

Pathology Publications

Background: Targeted next generation sequencing (NGS) technology to assess the mutational status of multiple genes on formalin-fixed, paraffin embedded (FFPE) tumors is rapidly being adopted in clinical settings, where quality control (QC) practices are required. Establishing reliable FFPE QC materials for NGS can be challenging and/or expensive. Here, we established a reliable and cost-effective FFPE QC material for routine utilization in the Ion AmpliSeq™ Cancer Hotspot Panel v2 (CHP2) assay.

Methods: The performance characteristics of the CHP2 assay were determined by sequencing various cell line mixtures and 55 different FFPE tumors on the Ion Torrent PGM platform. A FFPE QC …

Nosocomial Keratitis Caused By Methicillin-Resistant Staphylococcus Aureus: Case Report And Preventative Measures, Puneet S. Braich, Shruti Aggarwal, Sabrina Mukhtar, David Rp Almeida

Ophthalmology Publications

A 47-year-old African-American woman was admitted to the intensive care unit of our community hospital for respiratory failure secondary to severe decompensated heart failure, requiring intubation. In the ensuing days, she developed a methicillin-resistant Staphylococcus aureus (MRSA) infection of the cornea, despite no growth of MRSA in multiple blood, sputum, and urine cultures. This unexpected corneal infection complicated her hospital stay, and increased morbidity and disease-related cost. Risk factors, warning signs, and preventative measures for MRSA keratitis secondary to lagophthalmos (inability to completely close one's eyelids) are outlined in this case report. Implementing simple precautions such as taping eyelids shut …