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https://www.readbyqxmd.com/read/28078726/dissecting-the-cytochrome-p450-1a2-and-3a4-mediated-metabolism-of-aflatoxin-b1-in-ligand-and-protein-contributions
#1
Lars Olsen, Flemming S Jørgensen, Silvia Bonomo
Aflatoxin B1 (AFB1) is a chemically intriguing compound because it has several potential sites of metabolism (SOMs) while only some of them are observed experimentally. Cytochrome P450 (CYP) 3A4 and 1A2 are the major isoforms involved in its metabolism. Here, we systematically investigate reactivity and accessibility of all possible SOMs in these two CYPs to elucidate AFB1 metabolism. Density functional theory (DFT) calculations were used to determine activation energies for each possible reaction. Aliphatic hydroxylation on position 9A and 3α are energetically favored, whereas position 9 is the preferred site for epoxidation...
January 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28062685/development-and-validation-of-the-increment-esbl-predictive-score-for-mortality-in-patients-with-bloodstream-infections-due-to-extended-spectrum-%C3%AE-lactamase-producing-enterobacteriaceae
#2
Zaira Raquel Palacios-Baena, Belén Gutiérrez-Gutiérrez, Marina De Cueto, Pierluigi Viale, Mario Venditti, Alicia Hernández-Torres, Antonio Oliver, Luis Martínez-Martínez, Esther Calbo, Vicente Pintado, Oriol Gasch, Benito Almirante, José Antonio Lepe, Johann Pitout, Murat Akova, Carmen Peña-Miralles, Mitchell J Schwaber, Mario Tumbarello, Evelina Tacconelli, Julia Origüen, Nuria Prim, German Bou, Helen Giamarellou, Joaquín Bermejo, Axel Hamprecht, Federico Pérez, Manuel Almela, Warren Lowman, Po-Ren Hsueh, Carolina Navarro-San Francisco, Julián Torre-Cisneros, Yehuda Carmeli, Robert A Bonomo, David L Paterson, Álvaro Pascual, Jesús Rodríguez-Baño
BACKGROUND: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. METHODS: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC)...
January 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28024724/a-ppar-gamma-agonist-protects-against-oral-mucositis-induced-by-irradiation-in-a-murine-model
#3
Monica Mangoni, Mariangela Sottili, Chiara Gerini, Isacco Desideri, Cinzia Bastida, Stefania Pallotta, Francesca Castiglione, Pierluigi Bonomo, Icro Meattini, Daniela Greto, Emanuela Olmetto, Francesca Terziani, Carlotta Becherini, Camilla Delli Paoli, Laura Trombetta, Mauro Loi, Giampaolo Biti, Lorenzo Livi
BACKGROUND: Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis. MATERIAL AND METHODS: Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis...
January 2017: Oral Oncology
https://www.readbyqxmd.com/read/27998771/deficiency-in-ubiquitin-like-protein-ubl4a-impairs-migration-of-fibroblasts-and-macrophages
#4
Yu Zhao, Huaiyuan Zhang, Carlos Affonso, Raiza Bonomo, Adriana Mañas, Jialing Xiang
Ubiquitin-like protein Ubl4A is a small, multi-functional protein with no ubiquitination activity. We have previously demonstrated that Ubl4A directly interacts with actin-related protein 2/3 complex (Arp2/3) and promotes Arp2/3-dependent actin branching, thereby accelerating plasma membrane translocation of protein kinase Akt upon insulin stimulation. Here, we show that Ubl4A is critical for plasma membrane protrusion and cell migration. Ubl4A, F-actin and Arp2/3 are co-localized at the cell leading edges during wound closure...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27997706/exploring-the-potential-of-boronic-acids-as-inhibitors-of-oxa-24-40-%C3%AE-lactamase
#5
Josephine P Werner, Joshua M Mitchell, Magdalena A Taracila, Robert A Bonomo, Rachel A Powers
β-lactam antibiotics are crucial to the management of bacterial infections in the medical community. Due to overuse and misuse, clinically significant bacteria are now resistant to many commercially available antibiotics. The most widespread resistance mechanism to β-lactams is the expression of β-lactamase enzymes. To overcome β-lactamase mediated resistance, inhibitors were designed to inactivate these enzymes. However, current inhibitors (clavulanic acid, tazobactam, and sulbactam) for β-lactamases also contain the characteristic β-lactam ring, making them susceptible to resistance mechanisms employed by bacteria...
December 20, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27986347/subgroup-analysis-according-to-human-papillomavirus-status-and-tumor-site-of-a-randomized-phase-ii-trial-comparing-cetuximab-and-cisplatin-combined-with-radiation-therapy-for-locally-advanced-head-and-neck-cancer
#6
Michela Buglione, Marta Maddalo, Renzo Corvò, Luigi Pirtoli, Fabiola Paiar, Luciana Lastrucci, Marco Stefanacci, Liliana Belgioia, Monica Crociani, Stefania Vecchio, Pierluigi Bonomo, Silvia Bertocci, Paolo Borghetti, Nadia Pasinetti, Luca Triggiani, Loredana Costa, Sandro Tonoli, Salvatore Grisanti, Stefano Maria Magrini
PURPOSE: We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer. METHODS AND MATERIALS: The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites...
October 20, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27980781/critical-influence-of-the-thymus-on-peripheral-t-cell-homeostasis
#7
Pedro Henrique Oliveira Vianna, Fábio B Canto, Jeane S Nogueira, Caroline Fraga Cabral Gomes Nunes, Adriana César Bonomo, Rita Fucs
INTRODUCTION: A tight balance between regulatory CD4(+)Foxp3(+) (Treg) and conventional CD4(+)Foxp3(-) (Tconv) T cell subsets in the peripheral compartment, maintained stable throughout most of lifetime, is essential for preserving self-tolerance along with efficient immune responses. An excess of Treg cells, described for aged individuals, may critically contribute to their reported immunodeficiency. In this work, we investigated if quantitative changes in thymus emigration may alter the Treg/Tconv homeostasis regardless of the aging status of the peripheral compartment...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27974412/clinical-and-pathophysiological-overview-of-acinetobacter-infections-a-century-of-challenges
#8
REVIEW
Darren Wong, Travis B Nielsen, Robert A Bonomo, Paul Pantapalangkoor, Brian Luna, Brad Spellberg
SUMMARYAcinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity...
January 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/27965456/comprehensive-genome-analysis-of-carbapenemase-producing-enterobacter-spp-new-insights-into-phylogeny-population-structure-and-resistance-mechanisms
#9
Kalyan D Chavda, Liang Chen, Derrick E Fouts, Granger Sutton, Lauren Brinkac, Stephen G Jenkins, Robert A Bonomo, Mark D Adams, Barry N Kreiswirth
: Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1 Twenty-three isolates were carbapenem susceptible...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27957505/bacterial-colonization-and-antibiotic-resistance-in-a-prospective-cohort-of-newborn-infants-during-the-first-year-of-life
#10
Sharon B Meropol, Kurt C Stange, Michael R Jacobs, Judith K Weiss, Saralee Bajaksouzian, Robert A Bonomo
BACKGROUND: Infants are virtually sterile at birth and frequently use antibiotics; our objective was to (1) characterize the longitudinal colonization with bacterial pathogens and associated antibiotic resistance in a cohort of community-dwelling infants in Northeast Ohio and (2) describe longitudinal concurrent antibiotic and daycare exposures. METHODS: For 35 newborns, nasopharyngeal swabs were cultured for Streptococcus pneumoniae, anterior nasal for Staphylococcus aureus, and perirectal for extended-spectrum beta-lactamase (ESBL)-producing Gram-negative enteric bacteria, at 3-month intervals for 12 months...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27940944/colistin-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-laboratory-detection-and-impact-on-mortality
#11
Laura J Rojas, Madiha Salim, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Steve Marshall, Susan D Rudin, T Nicholas Domitrovic, Andrea M Hujer, Kristine M Hujer, Yohei Doi, Keith S Kaye, Scott Evans, Vance G Fowler, Robert A Bonomo, David van Duin
BACKGROUND: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. METHODS: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014...
December 10, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27931834/treatments-for-colorectal-liver-metastases-a-new-focus-on-a-familiar-concept
#12
REVIEW
M G Zampino, E Magni, P S Ravenda, C A Cella, G Bonomo, P Della Vigna, S Galdy, F Spada, G M Varano, G Mauri, N Fazio, F Orsi
A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27882934/macrophage-dependent-il-1%C3%AE-production-induces-cardiac-arrhythmias-in-diabetic-mice
#13
Gustavo Monnerat, Micaela L Alarcón, Luiz R Vasconcellos, Camila Hochman-Mendez, Guilherme Brasil, Rosana A Bassani, Oscar Casis, Daniela Malan, Leonardo H Travassos, Marisa Sepúlveda, Juan Ignacio Burgos, Martin Vila-Petroff, Fabiano F Dutra, Marcelo T Bozza, Claudia N Paiva, Adriana Bastos Carvalho, Adriana Bonomo, Bernd K Fleischmann, Antonio Carlos Campos de Carvalho, Emiliano Medei
Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27874958/diagnostic-accuracy-of-mdct-in-the-evaluation-of-patients-with-peritoneal-carcinomatosis-from-ovarian-cancer-is-delayed-enhanced-phase-really-effective
#14
E Rodolfino, E Devicienti, M Miccò, A Del Ciello, S E Di Giovanni, M Giuliani, C Conte, B Gui, A L Valentini, L Bonomo
OBJECTIVE: To assess the diagnostic accuracy of delayed enhanced phase in addition to portal enhanced phase in MDCT imaging for depicting peritoneal carcinomatosis (PC) implants in patients with ovarian cancer. PATIENTS AND METHODS: We retrospectively reviewed double-phase, portal enhanced phase (PEP) and delayed enhanced phase (DEP), MDCT-examinations of 40 patients with clinical suspicion of recurrent PC from histopathologically-proven ovarian cancer, previously treated with both cytoreductive surgery and adjuvant/neoadjuvant chemotherapy...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27874943/mr-enterography-with-diffusion-weighted-imaging-adc-values-in-normal-and-pathological-bowel-loops-a-possible-threshold-adc-value-to-differentiate-active-from-inactive-crohn-s-disease
#15
V Ninivaggi, M Missere, G Restaino, E Gangemi, M Di Matteo, A Pierro, G Sallustio, L Bonomo
OBJECTIVE: The aim of our study was to compare the apparent diffusion coefficient (ADC) values of pathological bowel loops wall (pADC) with the ADC values of normal appearing ones (naADC) and to determine a discriminating threshold. PATIENTS AND METHODS: 60 patients were studied at our Institution through a MR-enterography that included free-breathing axial Diffusion Weighted Imaging (DWI) with two b (0 and 800 s/mm2) after histological diagnosis of active Crohn's disease (CD)...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27872073/exploring-the-role-of-the-%C3%AE-loop-in-the-evolution-of-ceftazidime-resistance-in-the-pena-%C3%AE-lactamase-from-burkholderia-multivorans-an-important-cystic-fibrosis-pathogen
#16
Krisztina M Papp-Wallace, Scott A Becka, Magdalena A Taracila, Elise T Zeiser, Julian A Gatta, John J LiPuma, Robert A Bonomo
The unwelcome evolution of resistance to the advanced generation cephalosporin antibiotic, ceftazidime is hindering the effective therapy of Burkholderia cepacia complex (Bcc) infections. Regrettably, Bcc are highly resistant to most antibiotics, including polymyxins; ceftazidime and trimethoprim-sulfamethoxazole are the most effective treatment options. Unfortunately, resistance to ceftazidime is increasing and posing a health threat to populations susceptible to Bcc infection. We found that up to 36% of 146 tested Bcc clinical isolates were non-susceptible to ceftazidime...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27845566/the-potential-predictive-value-of-mri-and-pet-ct-in-mucinous-and-nonmucinous-rectal-cancer-to-identify-patients-at-high-risk-of-metastatic-disease
#17
Brunella Barbaro, Lucia Leccisotti, Fabio M Vecchio, Marialuisa Di Matteo, Teresa Serra, Marco Salsano, Andrea Poscia, Claudio Coco, Roberto Persiani, Sergio Alfieri, Maria Antonietta Gambacorta, Vincenzo Valentini, Alessandro Giordano, Lorenzo Bonomo
OBJECTIVE: To correlate imaging parameters from baseline MRI diffusion-weighted imaging (DWI) and fludeoxyglucose (FDG) positron emission tomography (PET)-CT with synchronous and metachronous metastases in mucinous carcinoma (MC) and non-mucinous carcinoma (NMC) rectal cancer. METHODS: 111 patients with extraperitoneal locally advanced rectal cancer, who underwent pelvic MRI, DWI and FDG PET-CT, were stratified into MC (n = 23) and NMC (n = 88). We correlated adverse morphologic features on MRI [mT4, mesorectal fascia involvement, extramural venous invasion (mEMVI), mN2] and quantitative imaging parameters [minimum apparent diffusion coefficient (ADCmin), maximum standardized uptake value, total lesion glycolysis, metabolic tumour volume, T2 weighted and DWI tumour volumes] with the presence of metastatic disease...
January 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/27844027/prosthetic-valve-endocarditis-caused-by-bartonella-henselae-a-case-report-of-molecular-diagnostics-informing-nonsurgical-management
#18
Patricia Bartley, Emmanouil Angelakis, Didier Raoult, Rangarajan Sampath, Robert A Bonomo, Robin L P Jump
Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27831654/unenhanced-breast-magnetic-resonance-imaging-detection-of-breast-cancer
#19
P Belli, E Bufi, A Bonatesta, F Patrolecco, F Padovano, M Giuliani, P Rinaldi, L Bonomo
OBJECTIVE: To evaluate the diagnostic performance of unenhanced MRI (UE-MRI) for malignant breast lesions and its reproducibility. PATIENTS AND METHODS: We retrospectively included 118 patients who had breast MRI. DWI and STIR images were read in combination and referred to as UE-MRI; the presence or absence of the malignant lesion was noted by two observers. Their results were compared with those of final histopathology or with a two-year negative follow-up for diagnostic performance assessment; ROC curves were built...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27809741/medicinal-cannabis-in-australia-the-missing-links
#20
Jennifer H Martin, Yvonne Bonomo
No abstract text is available yet for this article.
November 7, 2016: Medical Journal of Australia
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