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https://www.readbyqxmd.com/read/28292646/follow-up-of-elderly-patients-with-urogenital-cancers-evaluation-of-geriatric-care-needs-and-related-actions
#1
Silvio Monfardini, Sara Morlino, Riccardo Valdagni, Mario Catanzaro, Ardit Tafa, Barbara Bortolato, Giovanni Petralia, Elisa Bonetto, Elisa Villa, Stefano Picozzi, Maria Cristina Locatelli, Giuseppe Galetti, Andrea Millul, Yasmin Albanese, Elisa Bianchi, Claudia Panzarino, Francesca Gerardi, Ettore Beghi
OBJECTIVES: To investigate a comprehensive geriatric assessment (CGA) with subsequent investigation of healthcare patterns in older patients with urological cancers undergoing initial surgery or radiotherapy, to verify the usefulness of the incorporation of geriatric principles in future care plans. MATERIAL AND METHODS: This is a prospective cohort study. From November 2011 to March 2015, CGA was offered to all patients aged 70+ years treated with radiotherapy or surgery at seven tertiary centers...
March 11, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28262605/impulsivity-as-a-moderator-of-the-associations-between-child-maltreatment-types-and-body-mass-index
#2
Shaquanna Brown, Tarrah B Mitchell, Paula J Fite, Marco Bortolato
Child maltreatment has emerged as an important risk factor for adult obesity (Danese & Tan, 2014; Hemmingsson et al., 2014). However, there is a need for research delineating the factors that play a role in this association. Impulsivity has been shown to be associated with both child maltreatment (Brodsky et al., 2001) and body mass index (BMI; Cortese et al., 2008; Thamotharan et al., 2013). Further, given previous research showing that adverse events interact with impulsivity to predict hazardous drinking behaviors (Fox et al...
March 2, 2017: Child Abuse & Neglect
https://www.readbyqxmd.com/read/28237575/modeling-tics-in-rodents-conceptual-challenges-and-paths-forward
#3
Marco Bortolato, Christopher Pittenger
BACKGROUND: Recent advances in our understanding of the neurobiology of tics have led to the development of novel rodent models capturing different pathophysiological and phenotypic aspects of Tourette syndrome. The proliferation of these models, however, raises vexing questions on what standards should be adopted to assess their theoretical validity and empirical utility. Assessing the homology of a rodent motoric burst with a tic remains problematic, due to our incomplete knowledge of the underpinnings of tics, their high phenotypic complexity and variability, limitations in our ability test key aspects of tic phenomenology (such as premonitory sensory phenomena) in animals, and between-species differences in neuroanatomy and behavioral repertoire...
February 22, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28183242/decoding-corticotropin-releasing-factor-receptor-type-1-crystal-structures
#4
Andrew S Doré, Andrea Bortolato, Kaspar Hollenstein, Robert K Y Cheng, Randy J Read, Fiona H Marshall
The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28131725/the-5-alpha-reductase-inhibitor-finasteride-reduces-dyskinesia-in-a-rat-model-of-parkinson-s-disease
#5
Roberto Frau, Paola Savoia, Silvia Fanni, Chiara Fiorentini, Camino Fidalgo, Elisabetta Tronci, Roberto Stancampiano, Mario Meloni, Antonino Cannas, Francesco Marrosu, Marco Bortolato, Paola Devoto, Cristina Missale, Manolo Carta
Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramidal symptoms...
January 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28102229/the-neurosteroidogenic-enzyme-5%C3%AE-reductase-mediates-psychotic-like-complications-of-sleep-deprivation
#6
Roberto Frau, Valentina Bini, Alessio Soggiu, Simona Scheggi, Alessandra Pardu, Silvia Fanni, Paola Roncada, Monica Puligheddu, Francesco Marrosu, Donatella Caruso, Paola Devoto, Marco Bortolato
Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28099872/assessment-of-gait-and-sensorimotor-deficits-in-the-d1ct-7-mouse-model-of-tourette-syndrome
#7
Stephen C Fowler, Laura J Mosher, Sean C Godar, Marco Bortolato
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and phonic tics. While TS patients have been also shown to exhibit subtle abnormalities of sensorimotor integration and gait, animal models of this disorder are seldom tested for these functions. To fill this gap, we assessed gait and sensorimotor integration in the D1CT-7 mouse, one of the best-validated animal models of TS. D1CT-7 mice exhibit spontaneous tic-like manifestations, which, in line with the clinical phenomenology of TS, are markedly exacerbated by environmental stress...
January 15, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/27939782/what-makes-you-tic-translational-approaches-to-study-the-role-of-stress-and-contextual-triggers-in-tourette-syndrome
#8
REVIEW
Sean C Godar, Marco Bortolato
Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple, recurring motor and phonic tics. Rich empirical evidence shows that the severity of tics and associated manifestations is increased by several stressors and contextual triggers; however, the neurobiological mechanisms responsible for symptom exacerbation in TS remain poorly understood. This conceptual gap partially reflects the high phenotypic variability in tics, as well as the existing difficulties in operationalizing and standardizing stress and its effects in a clinical setting...
December 8, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27936453/biological-mechanisms-of-depression-following-treatment-with-interferon-for-chronic-hepatitis-c-a-critical-systematic-review
#9
REVIEW
Myrela O Machado, Giovanni Oriolo, Beatrice Bortolato, Cristiano A Köhler, Michael Maes, Marco Solmi, Iria Grande, Rocío Martín-Santos, Eduard Vieta, André F Carvalho
BACKGROUND: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. METHODS: Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment...
February 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27894012/depression-in-cancer-the-many-biobehavioral-pathways-driving-tumor-progression
#10
REVIEW
Beatrice Bortolato, Thomas N Hyphantis, Sara Valpione, Giulia Perini, Michael Maes, Gerwyn Morris, Marta Kubera, Cristiano A Köhler, Brisa S Fernandes, Brendon Stubbs, Nicholas Pavlidis, André F Carvalho
Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote: (1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic-pituitaryadrenal axis...
January 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27889491/pramipexole-enhances-disadvantageous-decision-making-lack-of-relation-to-changes-in-phasic-dopamine-release
#11
Romina Pes, Sean C Godar, Andrew T Fox, Lauren M Burgeno, Hunter J Strathman, David P Jarmolowicz, Paola Devoto, Beth Levant, Paul E Phillips, Stephen C Fowler, Marco Bortolato
Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc)...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27750143/exploring-the-neural-mechanisms-of-finasteride-a-proteomic-analysis-in-the-nucleus-accumbens
#12
Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada
The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia...
December 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27643714/identification-of-ligand-binding-hot-spots-of-the-histamine-h1-receptor-following-structure-based-fragment-optimization
#13
Sebastiaan Kuhne, Albert J Kooistra, Reggie Bosma, Andrea Bortolato, Maikel Wijtmans, Henry F Vischer, Jonathan S Mason, Chris de Graaf, Iwan J P de Esch, Rob Leurs
Developments in G protein-coupled receptor (GPCR) structural biology provide insights into GPCR-ligand binding. Compound 1 (4-(2-benzylphenoxy)piperidine) with high ligand efficiency for the histamine H1 receptor (H1R) was used to design derivatives to investigate the roles of (i) the amine-binding region, (ii) the upper and lower aromatic region, and (iii) binding site solvation. SAR analysis showed that the amine-binding region serves as the primary binding hot spot, preferably binding small tertiary amines...
October 13, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27541463/superdeformed-and-triaxial-states-in-42-ca
#14
K Hadyńska-Klȩk, P J Napiorkowski, M Zielińska, J Srebrny, A Maj, F Azaiez, J J Valiente Dobón, M Kicińska-Habior, F Nowacki, H Naïdja, B Bounthong, T R Rodríguez, G de Angelis, T Abraham, G Anil Kumar, D Bazzacco, M Bellato, D Bortolato, P Bednarczyk, G Benzoni, L Berti, B Birkenbach, B Bruyneel, S Brambilla, F Camera, J Chavas, B Cederwall, L Charles, M Ciemała, P Cocconi, P Coleman-Smith, A Colombo, A Corsi, F C L Crespi, D M Cullen, A Czermak, P Désesquelles, D T Doherty, B Dulny, J Eberth, E Farnea, B Fornal, S Franchoo, A Gadea, A Giaz, A Gottardo, X Grave, J Grȩbosz, A Görgen, M Gulmini, T Habermann, H Hess, R Isocrate, J Iwanicki, G Jaworski, D S Judson, A Jungclaus, N Karkour, M Kmiecik, D Karpiński, M Kisieliński, N Kondratyev, A Korichi, M Komorowska, M Kowalczyk, W Korten, M Krzysiek, G Lehaut, S Leoni, J Ljungvall, A Lopez-Martens, S Lunardi, G Maron, K Mazurek, R Menegazzo, D Mengoni, E Merchán, W Mȩczyński, C Michelagnoli, J Mierzejewski, B Million, S Myalski, D R Napoli, R Nicolini, M Niikura, A Obertelli, S F Özmen, M Palacz, L Próchniak, A Pullia, B Quintana, G Rampazzo, F Recchia, N Redon, P Reiter, D Rosso, K Rusek, E Sahin, M-D Salsac, P-A Söderström, I Stefan, O Stézowski, J Styczeń, Ch Theisen, N Toniolo, C A Ur, V Vandone, R Wadsworth, B Wasilewska, A Wiens, J L Wood, K Wrzosek-Lipska, M Ziȩbliński
Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in ^{42}Ca were determined from E2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 0_{2}^{+} has been obtained and the role of triaxiality in the A∼40 mass region is discussed...
August 5, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27458023/manic-symptom-severity-correlates-with-comt-activity-in-the-striatum-a-post-mortem-study
#15
Marco Bortolato, Consuelo Walss-Bass, Peter M Thompson, Jackob Moskovitz
OBJECTIVES: The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity...
July 26, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27312113/controlling-the-dissociation-of-ligands-from-the-adenosine-a2a-receptor-through-modulation-of-salt-bridge-strength
#16
Elena Segala, Dong Guo, Robert K Y Cheng, Andrea Bortolato, Francesca Deflorian, Andrew S Doré, James C Errey, Laura H Heitman, Adriaan P IJzerman, Fiona H Marshall, Robert M Cooke
The association and dissociation kinetics of ligands binding to proteins vary considerably, but the mechanisms behind this variability are poorly understood, limiting their utilization for drug discovery. This is particularly so for G protein-coupled receptors (GPCRs) where high resolution structural information is only beginning to emerge. Engineering the human A2A adenosine receptor has allowed structures to be solved in complex with the reference compound ZM241385 and four related ligands at high resolution...
July 14, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27111510/extra-helical-binding-site-of-a-glucagon-receptor-antagonist
#17
Ali Jazayeri, Andrew S Doré, Daniel Lamb, Harini Krishnamurthy, Stacey M Southall, Asma H Baig, Andrea Bortolato, Markus Koglin, Nathan J Robertson, James C Errey, Stephen P Andrews, Iryna Teobald, Alastair J H Brown, Robert M Cooke, Malcolm Weir, Fiona H Marshall
Glucagon is a 29-amino-acid peptide released from the α-cells of the islet of Langerhans, which has a key role in glucose homeostasis. Glucagon action is transduced by the class B G-protein-coupled glucagon receptor (GCGR), which is located on liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart and pancreas cells, and this receptor has been considered an important drug target in the treatment of diabetes. Administration of recently identified small-molecule GCGR antagonists in patients with type 2 diabetes results in a substantial reduction of fasting and postprandial glucose concentrations...
May 12, 2016: Nature
https://www.readbyqxmd.com/read/26958710/gpcr-bench-a-benchmarking-set-and-practitioners-guide-for-g-protein-coupled-receptor-docking
#18
Dahlia R Weiss, Andrea Bortolato, Benjamin Tehan, Jonathan S Mason
Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a publically available docking benchmarking set in the spirit of the DUD and DUD-E reference data sets for validation studies, containing 25 nonredundant high-resolution GPCR costructures with an accompanying set of diverse ligands and computational decoy molecules for each target...
April 25, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/26852938/altruistic-metadynamics-multisystem-biased-simulation
#19
Petr Hošek, Daniela Toulcová, Andrea Bortolato, Vojtěch Spiwok
We present a new simple extension of multiple walker metadynamics which makes it possible to simulate simultaneously multiple different molecular systems and to predict their free energy surfaces, named Altruistic metadynamics. Similarly to basic metadynamics, it uses a bias potential in the form of hills summed over the simulation. Each system adds a big hill to its "own" bias potential and smaller hills to bias potentials of other systems, hence, each system enhances sampling of other systems. This makes it possible to achieve either faster reaching of the stationary point or higher accuracy of the calculated free energy surfaces...
March 10, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/26812920/fibromyalgia-and-bipolar-disorder-emerging-epidemiological-associations-and-shared-pathophysiology
#20
REVIEW
B Bortolato, M Berk, M Maes, R S McIntyre, A F Carvalho
Fibromyalgia (FM) is a prevalent disorder defined by the presence of chronic widespread pain in association with fatigue, sleep disturbances and cognitive dysfunction. Recent studies indicate that bipolar spectrum disorders frequently co-occur in individuals with FM. Furthermore, shared pathophysiological mechanisms anticipate remarkable phenomenological similarities between FM and BD. A comprehensive search of the English literature was carried out in the Pubmed/MEDLINE database through May 10th, 2015 to identify unique references pertaining to the epidemiology and shared pathophysiology between FM and bipolar disorder (BD)...
2016: Current Molecular Medicine
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