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https://www.readbyqxmd.com/read/29313684/interfering-with-hur-rna-interaction-design-synthesis-and-biological-characterization-of-tanshinone-mimics-as-novel-effective-hur-inhibitors
#1
Leonardo Manzoni, Chiara Zucal, Danilo Di Maio, Vito G D'Agostino, Natthakan Thongon, Isabelle Bonomo, Preet Lal, Marco Miceli, Vanessa Baj, Marta Brambilla, Linda Cerofolini, Saioa Elezgarai, Emiliano Biasini, Claudio Luchinat, Ettore Novellino, Marco Fragai, Luciana Marinelli, Alessandro Provenzani, Pierfausto Seneci
The human antigen R (HuR) is an RNA-binding protein known to modulate the expression of target mRNA coding for proteins involved in inflammation, tumorigenesis and stress responses and is a valuable drug target. We previously found that Dihydrotanshinone-I (DHTS, 1) prevents the association of HuR with its RNA substrate, thus imparing its function. Herein, inspired by DHTS structure, we designed and synthesized an array of ortho-quinones (tanshinone mimics) using a function-oriented synthetic approach. Among others, compound 6a and 6n turned out to be more effective than 1, showing a nanomolar Ki and disrupting HuR binding to RNA in cells...
January 9, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29310479/therapies-for-multidrug-resistant-and-extensively-drug-resistant-non-fermenting-gram-negative-bacteria-causing-nosocomial-infections-a-perilous-journey-toward-molecularly-targeted-therapy
#2
Nadim G El Chakhtoura, Elie Saade, Alina Iovleva, Mohamad Yasmin, Brigid Wilson, Federico Perez, Robert A Bonomo
Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of "serious" by the Centers for Disease Control and Prevention. Two other major non-fermenting Gram-negative bacilli, Stenotrophomonas maltophilia and Burkholderia cepacia complex, while not as prevalent, have devastating effects on vulnerable populations, such as those with cystic fibrosis, as well as immunosuppressed or hospitalized patients...
January 9, 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29298737/a-feasible-model-for-early-intervention-for-high-risk-substance-use-in-the-emergency-department-setting
#3
Rebecca Howard, Stephanie Fry, Andrew Chan, Brigid Ryan, Yvonne Bonomo
Objective In response to escalating alcohol and other drug (AOD)-related emergency department (ED) presentations, a tertiary Melbourne hospital embedded experienced AOD clinical nurse consultants in the ED on weekends to trial a model for screening, assessment and brief intervention (BI). The aim of the present study was to evaluate the relative contributions of AOD to ED presentations and to pilot a BI model.Methods Using a customised AOD screening tool and a framework for proactive case finding, screened participants were offered a comprehensive AOD assessment and BI in the ED...
January 4, 2018: Australian Health Review: a Publication of the Australian Hospital Association
https://www.readbyqxmd.com/read/29279949/re-irradiation-with-curative-intent-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-a-national-survey-of-usual-practice-on-behalf-of-the-italian-association-of-radiation-oncology-airo
#4
Marta Maddalo, Pierluigi Bonomo, Liliana Belgioia, Almalina Bacigalupo, Vittorio Donato, Daniela Alterio, Ester Orlandi, Angela Argenone, Anna Merlotti, Daniela Musio, Marianna Trignani, Stefano Ursino, Stefano Arcangeli, Carlo Furlan, Mattia Falchetto Osti
OBJECTIVE: To report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck. METHODS: In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings...
December 26, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/29274468/molecular-characterization-of-carbapenem-resistant-enterobacter-cloacae-complex-in-colombia-blakpc-and-the-changing-landscape
#5
Elsa De La Cadena, Adriana Correa, Juan Sebastián Muñoz, Laura J Rojas, Cristhian Hernández-Gómez, Christian Pallares, Federico Perez, Robert A Bonomo, Maria V Villegas
OBJECTIVES: To examine the population structure of representative carbapenem resistant Enterobacter cloacae complex (CR-Ecl) isolates from 8 different Colombian regions and to characterize their asociated β-lactamases. METHODS: Twenty-eight CR-Ecl isolates collected in Colombia between 2009 and 2013 through the Colombian Nosocomial Network were included. Antimicrobial susceptibility testing was performed by broth microdilution. Molecular detection of carbapenemases and extended-spectrum β-lactamases (ESBL), and the presence of Tn4401 was evaluated by PCR and sequencing...
December 20, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29247871/simple-and-mixed-complexes-of-copper-ii-with-8-hydroxyquinoline-derivatives-and-amino-acids-characterization-in-solution-and-potential-biological-implications
#6
Carmelo Sgarlata, Giuseppe Arena, Raffaele P Bonomo, Alessandro Giuffrida, Giovanni Tabbì
Copper(II) complexes with 8-hydroxyquinoline (8-HQ) and two 8-HQ derivatives, namely clioquinol (CQ) and 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2), were investigated in organic and, where feasible, in aqueous solutions. This class of compounds is of particular interest in neurological disorders since they may act as metal-protein attenuating compounds and may help redistributing metal ions and restoring intracellular metal reserves, which are often perturbed in neurological patients. Several techniques, like potentiometry, UV-Vis absorption, electron paramagnetic resonance (EPR), cyclic voltammetry and electrospray ionisation-mass spectrometry (ESI-MS), were used to obtain information on both the formation of copper(II) complexes in solution as well as on the structure of their species...
December 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29239885/the-present-state-of-neurointensivist-training-in-the-united-states-a-comparison-to-other-critical-care-training-programs
#7
Evie G Marcolini, David B Seder, Jordan B Bonomo, Thomas P Bleck, J Claude Hemphill, Lori Shutter, Fred Rincon, Shelly D Timmons, Paul Nyquist
OBJECTIVE: This manuscript describes the state of neurocritical care fellowship training, compares its written standards to those of other critical care fellowship programs, and discusses how programmatic oversight by the United Council for Neurological Subspecialties should evolve to meet American College of Graduate Medical Education standards. This review is a work product of the Society of Critical Care Medicine Neuroscience section and was reviewed and approved by the Council of the Society of Critical Care Medicine...
December 12, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/29233788/day-case-laparoscopic-cholecystectomy-safety-and-feasibility-in-obese-patients-retrospective-cohort-study
#8
Matteo Gregori, Michelangelo Miccini, Daniele Biacchi, Jean-Charles deSchoutheete, Luca Bonomo, Antonio Manzelli
INTRODUCTION: Day-case laparoscopic cholecystectomy (DCLC) is not universally adopted and its use is limited to patients selected by non-standardized criteria. Since laparoscopic cholecystectomy is considered technically more difficult in obese patients, a high body mass index (BMI) is often considered an exclusion criterion for DCLC. The aim of this research is to define the feasibility and safety of day case laparoscopic cholecystectomy in obese patients. PRESENTATION OF CASE: Data from 730 consecutive patients preoperatively considered suitable for DCLC were analysed...
December 9, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/29230331/the-successful-treatment-of-a-case-of-linear-psoriasis-with-ixekizumab
#9
Sara Ghoneim, Alvaro J Ramos-Rodriguez, Fernando Vazquez de Lara, Lauren Bonomo
Linear psoriasis is an unusual clinical variation of psoriasis that manifests segmentally along the lines of Blaschko. A major differential diagnosis is inflammatory linear verrucous epidermal nevus (ILVEN). The treatment of linear psoriasis is often challenging, with inadequate response to biological agents reported in the literature. We report a case of a 25-year-old African-American female who presented with asymptomatic hyperkeratotic papules along the lines of Blaschko and was subsequently diagnosed with linear psoriasis...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/29229762/multiple-substitutions-lead-to-increased-loop-flexibility-and-expanded-specificity-in-acinetobacter-baumannii-carbapenemase-oxa-239
#10
Thomas M Harper, Cynthia M June, Magdalena A Taracila, Robert A Bonomo, Rachel A Powers, David A Leonard
OXA-239 is a class D carbapenemase isolated from an Acinetobacter baumannii strain found in Mexico.  This enzyme is a variant of OXA-23 with three amino acid substitutions in or near the active site.  These substitutions cause OXA-239 to hydrolyze late-generation cephalosporins and the monobactam aztreonam with greater efficiency than OXA-23.  OXA-239 activity against the carbapenems doripenem and imipenem is reduced approximately 3-fold and 20-fold respectively.  Further analysis demonstrated that two of the substitutions (P225S and D222N) are largely responsible for the observed alteration of kinetic parameters, while the third (S109L) may serve to stabilize the protein...
December 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29208480/robotic-stereotactic-retreatment-for-biochemical-control-in-previously-irradiated-patients-affected-by-recurrent-prostate-cancer
#11
M Loi, V Di Cataldo, G Simontacchi, B Detti, P Bonomo, L Masi, I Desideri, D Greto, G Francolini, V Carfora, D Pezzulla, M Perna, G A Carta, L Livi
AIMS: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. MATERIALS AND METHODS: Data from 50 patients were retrospectively reviewed...
December 2, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29201453/the-role-of-multimodal-treatment-in-patients-with-advanced-lung-neuroendocrine-tumors
#12
REVIEW
Nicola Fazio, Antonio Ungaro, Francesca Spada, Chiara Alessandra Cella, Eleonora Pisa, Massimo Barberis, Chiara Grana, Dario Zerini, Emilio Bertani, Dario Ribero, Luigi Funicelli, Guido Bonomo, Davide Ravizza, Juliana Guarize, Filippo De Marinis, Francesco Petrella, Ester Del Signore, Giuseppe Pelosi, Lorenzo Spaggiari
Lung neuroendocrine tumors (NETs) comprise typical (TC) and atypical carcinoids (AC). They represent the well differentiated (WD) or low/intermediate grade forms of lung neuroendocrine neoplasms (NENs). Unlike the lung poorly differentiated NENs, that are usually treated with chemotherapy, lung NETs can be managed with several different therapies, making a multidisciplinary interaction a key point. We critically discussed the multimodal clinical management of patients with advanced lung NETs. Provided that no therapeutic algorithm has been validate so far, each clinical case should be discussed within a NEN-dedicated multidisciplinary team...
November 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29198343/incidence-of-skin-toxicity-in-squamous-cell-carcinoma-of-the-head-and-neck-treated-with-radiotherapy-and-cetuximab-a-systematic-review
#13
REVIEW
Pierluigi Bonomo, Mauro Loi, Isacco Desideri, Emanuela Olmetto, Camilla Delli Paoli, Francesca Terziani, Daniela Greto, Monica Mangoni, Silvia Scoccianti, Gabriele Simontacchi, Giulio Francolini, Icro Meattini, Saverio Caini, Lorenzo Livi
PURPOSE: Radiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment. RESULTS: Forty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5-36.5) and 13.4% (SD: 11.5; 95% CI: 11...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29189372/multifunctional-assessment-of-non-small-cell-lung-cancer-perfusion-metabolic-correlation
#14
Lucio Calandriello, Anna Rita Larici, Lucia Leccisotti, Annemilia Del Ciello, Giuliano Sica, Amato Infante, Maria Teresa Congedo, Andrea Poscia, Alessandro Giordano, Lorenzo Bonomo
PURPOSE: The aim of this study was to investigate the relationship between whole-tumor CT perfusion and FDG PET/CT parameters in non-small cell lung cancer (NSCLC). METHODS: Twenty-five patients with NSCLC were prospectively included. CT perfusion parameters calculated were blood flow (BF), blood volume (BV), mean transit time, and peak enhancement intensity. SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated for PET/CT...
November 17, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29188018/atopic-dermatitis-patients-show-increases-in-serum-c-reactive-protein-levels-correlating-with-skin-disease-activity
#15
Anjali S Vekaria, Patrick M Brunner, Ahmad I Aleisa, Lauren Bonomo, Mark G Lebwohl, Ariel Israel, Emma Guttman-Yassky
Background: Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is evolving as a systemic disease, and associated systemic inflammation is possibly linked to increases in cardiovascular disease. Methods: We assessed levels of the inflammatory marker CRP in 59 patients with moderate-to-severe AD compared to matched healthy controls, and to determine correlation with skin disease severity. Clinical severity was measured using SCORing of Atopic Dermatitis (SCORAD) and body surface area (BSA)...
2017: F1000Research
https://www.readbyqxmd.com/read/29181422/carbapenem-resistant-enterobacteriaceae-infections-in-patients-on-renal-replacement-therapy
#16
Brandon Eilertson, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Yohei Doi, Keith S Kaye, Scott Evans, Vance G Fowler, Robert A Bonomo, Jack DeHovitz, Barry Kreiswirth, David van Duin
Background: Patients on chronic intermittent renal replacement therapy (RRT) are at risk for infection with carbapenem-resistant Enterobacteriaceae (CRE). However, the impact of RRT on outcomes after CRE infections remains to be defined. Here we perform a comparison of outcomes for CRE-infected patients with preserved renal function compared with CRE-infected patients on RRT. Methods: Cases and controls were defined from a prospective cohort of CRE-infected patients from the Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE)...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29168922/focused-ultrasound-tumor-ablation-and-its-potential-to-enhance-immunological-therapy-to-cancer
#17
Giovanni Mauri, Luca Nicosia, Zhen Xu, Salvatore Di Pietro, Lorenzo Monfardini, Guido Bonomo, Gianluca Maria Varano, Francesco Prada, Paolo Della Vigna, Franco Orsi
Various kind of image-guided techniques have been successfully applied in the last years for the treatment of tumours, as alternative to surgical resection. High Intensity focused ultrasound (HIFU) is a novel, totally non-invasive, image-guided technique that allow for achieving tissue destruction with the application of focused ultrasound at high intensity. This technique has been successfully applied for the treatment of a large variety of diseases, including oncological and non-oncological diseases. One of the most fascinating aspects of image-guided ablations, and particularly of HIFU, is the reported possibility of determining a sort of stimulation of the immune system, with an unexpected "systemic" response to treatments designed to be "local"...
November 23, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/29165604/carbapenemase-producing-organisms-a-global-scourge
#18
Robert A Bonomo, Eileen M Burd, John Conly, Brandi M Limbago, Laurent Poirel, Julie A Segre, Lars F Westblade
The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in health care environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort is needed to contain the risk of infection...
October 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29155481/peroxisome-proliferator-activated-receptor-gamma-stimulation-for-prevention-of-5-fluorouracil-induced-oral-mucositis-in-mice
#19
Mariangela Sottili, Monica Mangoni, Chiara Gerini, Giulia Salvatore, Francesca Castiglione, Isacco Desideri, Pierluigi Bonomo, Icro Meattini, Daniela Greto, Mauro Loi, Giulio Francolini, Marco Perna, Roberta Grassi, Giampaolo Biti, Lorenzo Livi
BACKGROUND: Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis. METHODS: C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected. RESULTS: The RGZ did not affect the 5-FU-induced decrease in mouse body weight...
November 20, 2017: Head & Neck
https://www.readbyqxmd.com/read/29144725/inhibition-of-acinetobacter-derived-cephalosporinase-adc-exploring-the-carboxylate-recognition-site-using-novel-%C3%AE-lactamase-inhibitors
#20
Emilia Caselli, Chiara Romagnoli, Rachel A Powers, Magdalena A Taracila, Alexandra A Bouza, Hollister C Swanson, Kali A Smolen, Francesco Fini, Bradley J Wallar, Robert A Bonomo, Fabio Prati
Boronic acids are attracting a lot of attention as -lactamase inhibitors, and in particular compound S02030 (Ki = 44 nM) proved to be a good lead compound against ADC-7 (Acinetobacter Derived Cephalosporinase), one of the most significant resistance determinants in A. baumannii. The atomic structure of the ADC-7/S02030 complex highlighted the importance of critical structural determinants for recognition of the boronic acids. Herein, to elucidate the role in recognition of the R2-carboxylate, which mimics the C3/C4 found in -lactams, we designed, synthesized, and characterized six derivatives of S02030 (3a)...
November 16, 2017: ACS Infectious Diseases
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