325 results on '"Mirabella, F"'
Search Results
102. X-ray photoemission study of manganese thin films deposited on a layered semiconductor.
- Author
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Mirabella, F., Parkinson, B. A., and Ghijsen, J.
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- 2004
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103. Airway cells after swimming outdoors or in the sea in nonasthmatic athletes.
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Bonsignore MR, Morici G, Riccobono L, Profita M, Bonanno A, Paternò A, Di Giorgi R, Chimenti L, Abate P, Mirabella F, Vignola AM, and Bonsignore G
- Published
- 2003
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104. Effect of cilomilast (Ariflo) on TNF-alpha, IL-8, and GM-CSF release by airway cells of patients with COPD.
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Profita, M, Chiappara, G, Mirabella, F, Di Giorgi, R, Chimenti, L, Costanzo, G, Riccobono, L, Bellia, V, Bousquet, J, and Vignola, A M
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BRONCHODILATOR agents ,PHOSPHODIESTERASE inhibitors ,CARBOXYLIC acids ,CELL culture ,CELL physiology ,COMPARATIVE studies ,ENZYME-linked immunosorbent assay ,EPITHELIAL cells ,GRANULOCYTE-macrophage colony-stimulating factor ,INTERLEUKINS ,OBSTRUCTIVE lung diseases ,RESEARCH methodology ,MEDICAL cooperation ,ORGANIC compounds ,RESEARCH ,RESPIRATORY mucosa ,SPUTUM ,TUMOR necrosis factors ,CYTOMETRY ,EVALUATION research ,CARBOCYCLIC acids ,THERAPEUTICS - Abstract
Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated.Methods: Bronchial epithelial cells obtained by bronchial brushing and sputum cells isolated from induced sputum samples were cultured for 24 hours in the presence or absence of cilomilast (1 micro M). After incubation the supernatants were harvested and the levels of mediators measured by ELISA. Chemotactic activity in supernatants was also measured using a Boyden chamber.Results: TNF-alpha and IL-8 release by bronchial epithelial cells and sputum cells was higher in patients with COPD than in controls (p<0.0001) and smokers (p<0.0001). GM-CSF was only detectable in sputum cell supernatants and its level was higher in patients with COPD than in controls and smokers (p<0.0001, respectively). Cilomilast significantly reduced TNF-alpha release by bronchial epithelial cells and sputum cells (p=0.005) and GM-CSF release by sputum cells (p=0.003), whereas IL-8 release was not statistically inhibited. Supernatants of sputum cells and bronchial epithelial cells treated with cilomilast significantly decreased neutrophil chemotaxis (p<0.006 and p<0.008, respectively).Conclusions: Cilomilast inhibits the production of some neutrophil chemoattractants by airway cells. This drug may play a role in the resolution of neutrophilic inflammation associated with COPD and cigarette smoke. [ABSTRACT FROM AUTHOR]- Published
- 2003
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- View/download PDF
105. Airway Remodeling in Asthma.
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Vignola, A.M., Mirabella, F., Costanzo, G., Di Giorgi, R., Gjomarkaj, M., Bellia, V., and Bonsignore, G.
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ASTHMA , *AIRWAY (Anatomy) , *INFLAMMATION - Abstract
Chronic inflammation and remodeling may follow acute inflammation or may begin insidiously as a low-grade smoldering response, especially in the case of immune reactions. The histologic hallmarks of chronic inflammation and remodeling are as follows: (1) infiltration by macrophages and lymphocytes; (2) proliferation of fibroblasts that may take the form of myofibroblasts; (3) angiogenesis; (4) increased connective tissue (fibrosis); and (5) tissue destruction. It is clear that changes in the extracellular matrix, smooth muscle, and mucous glands have the capacity to influence airway function and reactivity in asthma patients. However, it is not known how each of the many structural changes that occur in the airway wall contributes to altered airway function in asthma. In asthma, remodeling is almost always present in biopsy specimens (eg, collagen deposition on basement membrane) but is not always clinically demonstrated. Destruction and subsequent remodeling of the normal bronchial architecture are manifested by an accelerated decline in FEV[sub 1] and bronchial hyperresponsiveness. This irreversible component of airway obstruction is more prominent in patients with severe disease and even persists after aggressive anti-inflammatory treatment. Airway remodeling appears to be of great importance for understanding the long-term follow-up of asthmatic patients, but there are major gaps in our knowledge. Physiologic correlations with pathology represent a major missing link that should be filled. More long-term studies are needed to appreciate the prevention and treatment of remodeling. Future research therefore should provide better methods for limiting airway remodeling in asthma patients. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
106. Internal Reflection Spectroscopy.
- Author
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Mirabella, F. M.
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- 1985
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- View/download PDF
107. Photoemission study of Sn1-xMnxSe2
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Mirabella, F., Ghijsen, J., Johnson, R. L., Golacki, Z., and Orlowski, B. A.
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- 2001
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108. ^1^2^9Xe n.m.r. spectroscopic characterization of multiphase polypropylene copolymers
- Author
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Mirabella, F. M. and McFaddin, D. C.
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- 1996
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109. Treatment of multilesion coronary artery disease with simultaneous drug-eluting and bare-metal stent implantation: Clinical follow up and angiographic mid-term results
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Mirabella, F., Francaviglia, B., Capodanno, D., Di Salvo, M. E., Galassi, A. R., Ussia, G. P., Piera Capranzano, Tamburino, C., Mirabella F., Francaviglia B., Capodanno D., Di Salvo M.E., Galassi A.R., Ussia G.P., Capranzano P., and Tamburino C.
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multilesion ,disease ,artery ,coronary - Abstract
OBJECTIVES: We sought to evaluate clinical and angiographic outcomes of percutaneous coronary intervention (PCI) in patients receiving both bare-metal stents (BMS) and drug-eluting stents (DES). BACKGROUND: Few data are available about the safety and efficacy of the practice namely called "hybrid PCI". METHODS: One hundred and eighty-six patients, 502 de novo lesions, received during PCI both BMS (n ≤ 266) and DES (316), with a mean of 3.1 ± 1.2 stents/patient. Cumulative major adverse cardiac events were analyzed at 24 ± 22 months. RESULTS: Clinical follow up was carried out in 100 of eligible patients. Angiographic follow up at 8.6 ± 4.4 months was achieved in 70.4 of patients, 71.6 of stents and 72.5 of lesions. Binary restenosis was 12.9 vs. 20.6 (p ≤ 0.034) in DES vs. BMS, respectively; late loss was significantly higher in BMS than in DES (0.67 ± 0.73 vs. 0.35 ± 0.71 mm; p < 0.001). DES showed less lumen loss and binary restenosis rates than BMS in B2/C lesions (p < 0.001 and 0.007, respectively), while any significant difference was detected in A/B1 lesions (p ≤ 0.27 and 0.76, respectively). CONCLUSIONS: The simultaneous use of DES and BMS is safe and provides similar results for the 2 stents only in simple lesions. In complex lesions, BMS offer restenosis and a target lesion revascularization rates significantly higher than with DES.
110. Insights on the seismogenic layer thickness from the upper crust structure of the Umbria-Marche Apennines (Central Italy),Un contributo strutturale all'individuazione dello spessore dello strato sismogenetico in Appennino Settentrionale
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Mirabella, F., Lupattelli, A., Massimiliano Rinaldo BARCHI, Stucchi, E., and Ciaccio, M. G.
111. Accessibility and quality to health social services in Italy for the patients with rare diseases: the opinion of associations | Accessibilità e qualita dei servizi socio-sanitari italiani per i pazienti con malattie rare: il parere delle associazioni
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Agazio, E., Salerno, P., Mirabella, F., Gnessi, F., Mastroiacovo, P., Morosini, P., Tarsitani, G., and Domenica Taruscio
112. Italian validation of the Frommelt Attitudes Toward Care of the Dying Scale form B (FACTOD form B-I) | Validazione Italiana del Frommelt Attitudes Toward Care of the Dying Scale form B (FACTOD form B-I)
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Mastroianni, C., Piredda, M., Frommelt, K. H. M., Mirabella, F., Taboga, C., Casale, G., and Maria Grazia De Marinis
113. Frommelt Attitudes Toward Care of the Dying Scale Form B: psychometric testing of the Italian version for students
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Mastroianni C, Piredda M, Taboga C, Mirabella F, Marfoli E, Casale G, Maria Matarese, Kh, Frommelt, and Mg, Marinis
114. Lithological and mechanical control on the base of the crustal seismogenic zone: A case-study from the Northern Apennines of Italy
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Massimiliano Rinaldo BARCHI, Collettini, C., Paola, N., Faulkner, D., Lupattelli, A., Mirabella, F., and Trippetta, F.
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anhydrites ,seismic reflection profiles ,laboratory tests ,seismogenic layer ,upper crust
115. Pressure ulcers in elderly palliative care patients.
- Author
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de Marinis, Maria Grazia, Piredda, Michela, Hendrichova, Ilona, Mastroianni, Chiara, Casale, Giuseppe, Esposito, Giuseppe, Castelli, M, Surdo, L, and Mirabella, F
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- 2010
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116. High-resolution photoelectron spectroscopy studies on WO3 films modified by Ag addition.
- Author
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Bittencourt, C., Felten, A., Mirabella, F., Ivanov, P., Llobet, E., Silva, M. A. P., Nunes, L. A. O., and Pireaux, J. J.
- Published
- 2005
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117. Interleukin-4 promotes airway remodeling in asthma: regulation of procollagen I (alpha1) gene by interleukin-4.
- Author
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Vignola AM, Mirabella F, Costanzo G, Di Giorgi R, Gjomarkaj M, Bellia V, Bonsignore G, Bergeron, Céline, Pagé, Nathalie, Barbeau, Benoit, and Chakir, Jamila
- Abstract
Chronic inflammation and remodeling may follow acute inflammation or may begin insidiously as a low-grade smoldering response, especially in the case of immune reactions. The histologic hallmarks of chronic inflammation and remodeling are as follows: (1) infiltration by macrophages and lymphocytes; (2) proliferation of fibroblasts that may take the form of myofibroblasts; (3) angiogenesis; (4) increased connective tissue (fibrosis); and (5) tissue destruction. It is clear that changes in the extracellular matrix, smooth muscle, and mucous glands have the capacity to influence airway function and reactivity in asthma patients. However, it is not known how each of the many structural changes that occur in the airway wall contributes to altered airway function in asthma. In asthma, remodeling is almost always present in biopsy specimens (eg, collagen deposition on basement membrane) but is not always clinically demonstrated. Destruction and subsequent remodeling of the normal bronchial architecture are manifested by an accelerated decline in FEV(1) and bronchial hyperresponsiveness. This irreversible component of airway obstruction is more prominent in patients with severe disease and even persists after aggressive anti-inflammatory treatment. Airway remodeling appears to be of great importance for understanding the long-term follow-up of asthmatic patients, but there are major gaps in our knowledge. Physiologic correlations with pathology represent a major missing link that should be filled. More long-term studies are needed to appreciate the prevention and treatment of remodeling. Future research therefore should provide better methods for limiting airway remodeling in asthma patients. [ABSTRACT FROM AUTHOR]
- Published
- 2003
118. Impact polypropylene copolymers: fractionation and structural characterization
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Mirabella, F. M.
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- 1993
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119. The enhancement of activity rescues the establishment of Mecp2 null neuronal phenotypes
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Massimiliano Pagani, Davide Pozzi, Linda Scaramuzza, M. De Simone, D. Genni, Filippo Mirabella, Fabio Benfenati, Fabrizia Cesca, Nicoletta Landsberger, G. De Rocco, C. G. Clementina, Martina Chiacchiaretta, Paola Conforti, Francesco Bedogni, Scaramuzza, L., De Rocco, G., Desiato, G., Cobolli Gigli, C., Chiacchiaretta, M., Mirabella, F., Pozzi, D., De Simone, M., Conforti, P., Pagani, M., Benfenati, F., Cesca, F., Bedogni, F., and Landsberger, N.
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0301 basic medicine ,Ampakine ,Medicine (General) ,congenital, hereditary, and neonatal diseases and abnormalities ,Offspring ,medicine.drug_class ,Methyl-CpG-Binding Protein 2 ,Rett syndrome ,Biology ,QH426-470 ,Article ,neuronal activity ,MECP2 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neurodevelopmental disorder ,R5-920 ,neuronal maturation ,In vivo ,Transcription (biology) ,medicine ,Genetics ,Premovement neuronal activity ,Animals ,Humans ,Gene ,Mecp2 ,030304 developmental biology ,Neurons ,0303 health sciences ,Brain ,Articles ,medicine.disease ,Phenotype ,3. Good health ,030104 developmental biology ,nervous system ,Molecular Medicine ,Female ,Genetics, Gene Therapy & Genetic Disease ,Neuroscience ,030217 neurology & neurosurgery - Abstract
MECP2 mutations cause Rett syndrome (RTT), a severe and progressive neurodevelopmental disorder mainly affecting females. Although RTT patients exhibit delayed onset of symptoms, several evidences demonstrate that MeCP2 deficiency alters early development of the brain. Indeed, during early maturation, Mecp2 null cortical neurons display widespread transcriptional changes, reduced activity, and defective morphology. It has been proposed that during brain development these elements are linked in a feed‐forward cycle where neuronal activity drives transcriptional and morphological changes that further increase network maturity. We hypothesized that the enhancement of neuronal activity during early maturation might prevent the onset of RTT‐typical molecular and cellular phenotypes. Accordingly, we show that the enhancement of excitability, obtained by adding to neuronal cultures Ampakine CX546, rescues transcription of several genes, neuronal morphology, and responsiveness to stimuli. Greater effects are achieved in response to earlier treatments. In vivo, short and early administration of CX546 to Mecp2 null mice prolongs lifespan, delays the disease progression, and rescues motor abilities and spatial memory, thus confirming the value for RTT of an early restoration of neuronal activity., Neuronal activity drives transcriptional and morphological changes that ensure maturation. Such mechanism is affected by Mecp2 absence. We show the rescue effects produced by enhancing Mecp2 null neurons activity and propose new therapeutic time windows for the treatment of Rett syndrome.
- Published
- 2021
120. Revealing the innermost nanostructure of sputtered NiCrO x solar absorber cermets.
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Gaouyat, L., He, Z., Colomer, J.-F., Lambin, Ph., Mirabella, F., Schryvers, D., and Deparis, O.
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NANOSTRUCTURED materials , *SPUTTERING (Physics) , *NICKEL-chromium alloys , *CHROMIUM oxide , *SOLAR energy , *SOLAR absorber-convertors , *CERAMIC metals , *ENERGY conversion - Abstract
Abstract: Conversion of solar energy into thermal energy helps reducing consumption of non-renewable energies. Cermets (ceramic–metal composites) are versatile materials suitable, amongst other applications, for solar selective absorbers. Although the presence of metallic Ni particles in the dielectric matrix is a prerequisite for efficient solar selective absorption in NiCrOx cermets, no clear evidence of such particles is reported so far. By combining comprehensive chemical and structural analyses, we reveal the presumed nanostructure which is at the origin of the remarkable optical properties of this cermet material. Using sputtered NiCrO x layers in a solar absorber multilayer stack on aluminium substrate allows us to achieve solar absorptance as high as α=96.1% while keeping thermal emissivity as low as ε=2.2%, both values being comparable to best values recorded so far. With the nanostructure of sputtered NiCrO x cermets eventually revealed, further optimization of solar absorbers can be anticipated and technological exploitation of cermet materials in other applications can be foreseen. [Copyright &y& Elsevier]
- Published
- 2014
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121. Optical properties of thermochromic VO2 thin films on stainless steel: Experimental and theoretical studies
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Lafort, A., Kebaili, H., Goumri-Said, S., Deparis, O., Cloots, R., De Coninck, J., Voué, M., Mirabella, F., Maseri, F., and Lucas, S.
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OPTICAL properties , *THIN films , *THERMOCHROMISM , *VANADIUM oxide , *STAINLESS steel , *EXPERIMENTAL design , *MAGNETRON sputtering , *SUBSTRATES (Materials science) , *ELLIPSOMETRY , *SPECTRAL reflectance , *THICKNESS measurement - Abstract
Abstract: Thermochromic films of VO2 were deposited by DC reactive magnetron sputtering on stainless steel substrate. Complex refractive indexes of VO2 were determined by ellipsometric spectroscopy (0.35–16.5μm) for different film thicknesses. Optical simulations were performed to model the spectral reflectance of the film/substrate system for a film thickness of 100nm and 200nm and to monitor the optical contrast of the thermochromic layers by comparing the spectral reflectance at 25°C and 100°C. The good agreement observed between experimental and theoretical spectra demonstrates the adequacy of the model for predicting the optical properties of the samples. [Copyright &y& Elsevier]
- Published
- 2011
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122. Surface and electronic structure of Ga0.92In0.08N thin film investigated by photoelectron spectroscopy
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Kowalski, B.J., Kowalik, I.A., Iwanowski, R.J., Sadowski, J., Kanski, J., Orlowski, B.A., Ghijsen, J., Mirabella, F., Lusakowska, E., Perlin, P., Porowski, S., Grzegory, I., and Leszczynski, M.
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SURFACES (Technology) , *ELECTRONIC structure , *PHOTOELECTRON spectroscopy , *PHOTOELECTRICITY - Abstract
Abstract: The surface and electronic structure of Ga0.92In0.08N layers grown by metal organic chemical vapor deposition (MOCVD) have been investigated by means of photoemission. Stability of chemical composition of the surface subjected to Ar+ ion sputtering was proven by means of X-ray photoemission spectroscopy. The analysis of the relative intensities of In 3d, Ga 3p, and N 1s peaks showed that argon ion bombardment does not change significantly the relative contents of the layer constituents. Simultaneous efficient removal of the main contaminants (O and C) was observed during the sputtering procedure, proving that argon sputtering can be used as a method for preparation of clean Ga1−x In x N surfaces. For a clean (0001)–(1×1) surface prepared by repeated cycles of Ar+ ion sputtering and annealing, electronic structure was investigated. The band structure was explored along the Γ–A direction of the Brillouin zone, measuring angle-resolved photoemission spectra along the surface normal. A similar set of data was also acquired for the same surface of GaN layer. Comparison of the collected data revealed an additional feature at the valence band edge, which can be ascribed to the presence of In in the layer. [Copyright &y& Elsevier]
- Published
- 2005
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123. X-ray and ultraviolet photoemission study of electronic structure of <f>Sn1−xMnx</f>Te MBE layers
- Author
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Orlowski, B.A., Mickevičius, S., Kowalski, B.J., Nadolny, A.J., Taliashvili, B., Ghijsen, J., Mirabella, F., and Johnson, R.L.
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ELECTRONIC structure , *MOLECULAR beam epitaxy - Abstract
X-ray photoelectron and ultraviolet resonant photoemission spectroscopy was used to study the
Sn0.96Mn0.04 Te MBE layers. The surface chemical composition of the samples after different treatment conditions was studied by means of XPS. Resonant photoemission spectroscopy with application of the synchrotron radiation was applied to investigate the electronic structure and the contribution of Mn 3d electrons to the valence band ofSn0.96Mn0.04 Te layers. The contribution of the Mn 3d electrons to the valence band electronic structure appears at the valence band with the maximum located at 4.0 eV below the valence band edge. [Copyright &y& Elsevier]- Published
- 2002
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124. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms
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Ramón García-Sanz, David Gonzalez, Lisa Murray, Norma C. Gutiérrez, David Bentley, Mark T. Ross, Jesús F. San Miguel, Martin Kaiser, Annamaria Brioli, Christopher P. Wardell, David W. Johnson, Faith E. Davies, Fabio Mirabella, Sean Humphray, Gareth J. Morgan, Brian A Walker, Lucía López-Corral, Lorenzo Melchor, Walker BA, Wardell CP, Melchor L, Brioli A, Johnson DC, Kaiser MF, Mirabella F, Lopez-Corral L, Humphray S, Murray L, Ross M, Bentley D, Gutiérrez NC, Garcia-Sanz R, San Miguel J, Davies FE, Gonzalez D, and Morgan GJ
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Cancer Research ,medicine.medical_specialty ,Pathology ,Biology ,Monoclonal Gammopathy of Undetermined Significance ,Article ,Translocation, Genetic ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Exome ,genome ,Multiple myeloma ,Plasma cell leukemia ,Hematology ,sequencing ,medicine.disease ,Lymphoma ,Leukemia ,myeloma ,Cell Transformation, Neoplastic ,Oncology ,Mutation ,Cancer research ,Disease Progression ,smoldering ,progression ,Clone (B-cell biology) ,Multiple Myeloma ,Monoclonal gammopathy of undetermined significance - Abstract
The mechanisms involved in the progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia (PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole-genome sequencing on a series of MGUS (n=4), high-risk (HR)SMM (n=4), MM (n=26) and PCL (n=2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors that drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease, the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage.
- Published
- 2013
125. Clinical and Biological Heterogeneity in Children with Moderate Asthma
- Author
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Stefania La Grutta, Giovanni Battista Pajno, Jean Bousquet, Giovanni Bonsignore, Rosalia Gagliardo, Franco Mirabella, Antonio M. Vignola, Vincenzo Bellia, La Grutta, S, Gagliardo, R, Mirabella, F, Pajno, G, Bonsignore, G, Bousquet, J, Bellia, V, and Vignola, A
- Subjects
Male ,Exacerbation ,Anti-Inflammatory Agents ,Critical Care and Intensive Care Medicine ,Synaptotagmins ,Medicine ,Child ,Salmeterol Xinafoate ,Calcium-Binding Protein ,Membrane Glycoproteins ,Respiratory disease ,NF-kappa B ,inflammatory markers ,Bronchodilator Agents ,Anti-Inflammatory Agent ,Synaptotagmin I ,Biomarker (medicine) ,Female ,Membrane Glycoprotein ,Androstadienes ,Leukocytes, Mononuclear ,Granulocyte-Macrophage Colony-Stimulating Factor ,Humans ,Albuterol ,Asthma ,Receptors, Cell Surface ,Nerve Tissue Proteins ,Nitric Oxide ,Calcium-Binding Proteins ,Interleukin-8 ,Adolescent ,Biological Markers ,medicine.symptom ,Human ,medicine.drug ,Pulmonary and Respiratory Medicine ,Inflammation ,Peripheral blood mononuclear cell ,Fluticasone propionate ,Bronchodilator Agent ,Androstadiene ,fluticasone propionate ,business.industry ,medicine.disease ,Synaptotagmin ,asthma ,Nerve Tissue Protein ,Biological Marker ,Exhaled nitric oxide ,Immunology ,Fluticasone ,business ,Biomarkers - Abstract
To evaluate the relationship between inflammatory markers and severity of asthma in children, the amount of interleukin-8 (IL-8) and granulocyte/macrophage colony-stimulating factor (GM-CSF) released by peripheral blood mononuclear cells, exhaled nitric oxide (FE NO) levels, p65 nuclear factor-kappaB subunit, and phosphorylated IkBalpha expression by peripheral blood mononuclear cells were assessed in six control subjects, 12 steroid-naives subjects with intermittent asthma, and 17 children with moderate asthma. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18-month follow-up period. We found that GM-CSF release was higher in moderate and intermittent asthmatics than in control subjects, whereas IL-8 release was higher in moderate than in intermittent asthmatics and control subjects. FE NO levels were similar among study groups. In moderate asthmatics, IL-8, GM-CSF, and FE NO significantly correlated with the exacerbation numbers. Moreover, p65 and phosphorylated IkBalpha levels were greater in moderate than in intermittent asthmatics and control subjects. According to GM-CSF, IL-8, and FE NO levels, two distinct subgroups of moderate asthmatics (low and high producers) were identified. High producers experienced more exacerbations than low producers. This study shows ongoing inflammation associated with biological and clinical heterogeneity in moderate asthmatics despite regular treatment and proposes that large prospective studies confirm the importance of biomarkers to assess inflammation and asthma control in children with asthma.
- Published
- 2003
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126. Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma
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Brian A Walker, Martin Kaiser, Lorenzo Melchor, Fabio Mirabella, Faith E. Davies, Gareth J. Morgan, Ping Wu, Christopher P. Wardell, David W. Johnson, Annamaria Brioli, Kaiser MF, Johnson DC, Wu P, Walker BA, Brioli A, Mirabella F, Wardell CP, Melchor L, Davies FE, and Morgan GJ
- Subjects
Adult ,Male ,Immunology ,Biology ,Decitabine ,Bioinformatics ,Biochemistry ,Epigenesis, Genetic ,Transforming Growth Factor beta1 ,MULTIPLE MYELOMA ,Gene expression ,medicine ,Humans ,Genes, Tumor Suppressor ,Osteonectin ,Gene ,Multiple myeloma ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,Regulation of gene expression ,Lymphoid Neoplasia ,Gene Expression Profiling ,Tumor Suppressor Proteins ,Cell Biology ,Hematology ,Methylation ,DNA Methylation ,Middle Aged ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Phenotype ,DNA methylation ,Azacitidine ,Disease Progression ,Cancer research ,Female ,TGFBI - Abstract
Outcome in multiple myeloma is highly variable and a better understanding of the factors that influence disease biology is essential to understand and predict behavior in individual patients. In the present study, we analyzed combined genomewide DNA methylation and gene expression data of patients treated in the Medical Research Council Myeloma IX trial. We used these data to identify epigenetically repressed tumor suppressor genes with prognostic relevance in myeloma. We identified 195 genes with changes in methylation status that were significantly associated with prognosis. Combining DNA methylation and gene expression data led to the identification of the epigenetically regulated tumor modulating genes GPX3, RBP1, SPARC, and TGFBI. Hypermethylation of these genes was associated with significantly shorter overall survival, independent of age, International Staging System score, and adverse cytogenetics. The 4 differentially methylated and expressed genes are known to mediate important tumor suppressive functions including response to chemotherapy (TGFBI), interaction with the microenvironment (SPARC), retinoic acid signaling (RBP1), and the response to oxidative stress (GPX3), which could explain the prognostic impact of their differential methylation. Assessment of the DNA methylation status of the identified genes could contribute to the molecular characterization of myeloma, which is prerequisite for an individualized treatment approach.
- Published
- 2013
127. Real world safety and efficacy of the Janus Tacrolimus-Eluting stent: long-term clinical outcome and angiographic findings from the Tacrolimus-Eluting STent (TEST) registry
- Author
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Damiana Fiscella, Davide Capodanno, Piera Capranzano, Francesca Mirabella, George Dangas, Rosario Parisi, Francesco Scardaci, Roxana Mehran, Maria Elena Di Salvo, Gianpaolo Ussia, Alfredo R. Galassi, Corrado Tamburino, Tamburino C., Di Silvo M.E., Capodanno D., Capranzano P., Parisi R., Mirabella F., Scardaci F., Ussia G., Galassi A.R., Fiscella D., Mehran R., and Dangas G.
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Population ,Myocardial Infarction ,Restenosi ,Kaplan-Meier Estimate ,Coronary Angiography ,Prosthesis Design ,Risk Assessment ,Tacrolimus ,Coronary Restenosis ,Restenosis ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Myocardial infarction ,Prospective Studies ,Registries ,Angioplasty, Balloon, Coronary ,education ,Aged ,education.field_of_study ,business.industry ,Coronary Stenosis ,Stent ,Percutaneous coronary intervention ,Tacrolimus eluting stent ,Cardiovascular Agents ,Drug-Eluting Stents ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Antiproliferative Agents ,Female ,Radiology ,Safety ,Cardiology and Cardiovascular Medicine ,business ,Mace - Abstract
Objectives: We sought to evaluate the safety and performance of the Janus Tacrolimus-Eluting stent (TES) in an unselected population of patients, without application of restrictive clinical or angiographic criteria. Background: Continued attention to the safety, efficacy, and deliverability of first-generation drug eluting stents has led to the development of new antiproliferative agents with alternative stent platforms and different drug carrier vehicles. Methods: The TEST (Tacrolimus Eluting STent) registry is a prospective, nonrandomized single-center registry in which 140 consecutive patients who underwent single- or multi-vessel percutaneous coronary intervention between February 2005 and August 2005 were enrolled. Results: The composite rate of major adverse cardiac events (MACE) at 22 months clinical follow-up was 40.9%. The rate of mortality, myocardial infarction, and target lesion revascularization (TLR) were 5.5%, 11%, and 31.5%, respectively. Angiographic follow-up at 8 months was achieved in 74% of patients; binary restenosis occurred in 39.4% of lesions. Most restenosis lesions (94.6%) had a diffuse pattern, while focal restenosis was observed in 5.4% of cases. Definite or probable stent thrombosis was observed in 2.4% of patients. Conclusions: The present prospective, nonrandomized, TEST registry indicated high MACE and restenosis rates, and thereby rather discouraging long-term outcomes with use of the Janus TES in an unselected “real world” population of patients who underwent single- or multi-vessel percutaneous coronary intervention. © 2009 Wiley-Liss, Inc.
- Published
- 2009
128. Airway cell composition at rest and after an all-out test in competitive rowers
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Franco Mirabella, Rossana Di Giorgi, Antonio M. Vignola, Giuseppe Amato, Giuseppe Morici, Laura Chimenti, Maria R. Bonsignore, Anna Bonanno, Giovanni Bonsignore, Mirella Profita, Alessandra Paternò, Loredana Riccobono, Vincenzo Bellia, Arcangelo Benigno, Daniele Zangla, MORICI G, BONSIGNORE MR, ZANGLA D, RICCOBONO L, PROFITA M, BONANNO A, PATERNO' A, DI GIORGI R, MIRABELLA F, CHIMENTI L, BENIGNO A, VIGNOLA AM, BELLIA V, AMATO G, and BONSIGNORE G
- Subjects
Male ,medicine.medical_specialty ,Molecular composition ,Adolescent ,Neutrophils ,Rest ,Rowing ,Physical Therapy, Sports Therapy and Rehabilitation ,Bronchi ,Cell Count ,Oxygen Consumption ,Internal medicine ,Albumins ,Macrophages, Alveolar ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Exercise ,Rest (music) ,business.industry ,Pulmonary Gas Exchange ,Sputum ,Mean age ,Epithelial Cells ,Bronchial Epithelial Cell ,Physical therapy ,Cardiology ,Breathing ,Female ,Airway ,business ,Leukocyte Elastase ,Cell Adhesion Molecules ,Sports - Abstract
Med Sci Sports Exerc. 2004 Oct;36(10):1723-9. Airway cell composition at rest and after an all-out test in competitive rowers. Morici G, Bonsignore MR, Zangla D, Riccobono L, Profita M, Bonanno A, Paternò A, Di Giorgi R, Mirabella F, Chimenti L, Benigno A, Vignola AM, Bellia V, Amato G, Bonsignore G. SourceDepartment of Experimental Medicine Italian National Research Council (CNR), Palermo, Italy. Abstract PURPOSES: This study was designed to assess: a) whether rowing affects airway cell composition, and b) the possible relationship between the degree of ventilation during exercise and airway cells. SUBJECTS AND METHODS: In nine young, nonasthmatic competitive rowers (mean age +/- SD: 16.2 +/- 1.0 yr), induced sputum samples were obtained at rest and shortly after an all-out rowing test over 1000 m (mean duration: 200 +/- 14 s), during which ventilatory and metabolic variables were recorded breath-by-breath (Cosmed K4b, Italy). RESULTS: At rest, induced sputum showed prevalence of neutrophils (60%) over macrophages (40%); after exercise, total cell and bronchial epithelial cell (BEC) counts tended to increase. In the last minute of exercise, mean VE was 158.0 +/- 41.5 L x min(-1), and VO2 x kg(-1) 62 +/- 11 mL x min(-1). Exercise VE correlated directly with postexercise total cell (Spearman rho: 0.75, P < 0.05) an dmacrophage (rho: 0.82, P < 0.05) counts. A similar trend was observed for exercise VE and changes in BEC counts from baseline to postexercise (rho: 0.64, P = 0.11). Exercise VE did not correlate with airway neutrophil counts at rest or after exercise. Expression of adhesion molecules by airway neutrophils, macrophages, and eosinophils decreased after the all-out test. CONCLUSION: Similar to endurance athletes, nonasthmatic competitive rowers showed increased neutrophils in induced sputum compared with values found in sedentary subjects. The trend toward increased BEC postexercise possibly reflected the effects of high airflows on airway epithelium. Airway macrophages postexercise were highest in rowers showing tile most intense exercise hyperpnea, suggesting early involvement of these cells during exercise. However, the low expression of adhesion molecules by all airway cell types suggests that intense short-lived exercise may be associated with a blunted response of airway cells in nonasthmatic well-trained rowers. PMID:15595293[PubMed - indexed for MEDLINE]
- Published
- 2004
129. Circulating hematopoietic progenitor cells in runners
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Lucia Cascio, Giuseppe Insalaco, Maria R. Bonsignore, Ugo Testa, Ignazio Majolino, Mirella Profita, James C. Hogg, Franco Mirabella, Alessandra Santoro, Pietro Abate, Gioia M, A. Maurizio Vignola, Giuseppe Morici, Maria Pagano, Anna Bonanno, Bonsignore, M., Morici, G., Santoro, A., Pagano, M., Cascio, L., Bonanno, A., Abate, P., Mirabella, F., Profita, M., Insalaco, G., Gioia, M., Vignola, A., Majolino, I., Testa, U., and Hogg, J.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Marathon ,Time Factors ,Hydrocortisone ,Physiology ,medicine.medical_treatment ,Physical Therapy, Sports Therapy and Rehabilitation ,Antigens, CD34 ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Settore BIO/09 - Fisiologia ,Running ,Endocrinology ,Reference Values ,Endurance training ,Physiology (medical) ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Orthopedics and Sports Medicine ,Progenitor cell ,Cytokine ,Blood Cells ,Physical Education and Training ,Hematopoietic cell ,Interleukin-6 ,business.industry ,Growth factor ,Membrane Proteins ,Middle Aged ,Hematopoietic Stem Cells ,Blood Cell Count ,medicine.anatomical_structure ,embryonic structures ,Immunology ,Physical Endurance ,Hematopoietic progenitor cells ,Bone marrow ,Cytokines ,Growth factors ,business ,human activities - Abstract
Because endurance exercise causes release of mediators and growth factors active on the bone marrow, we asked whether it might affect circulating hematopoietic progenitor cells (HPCs) in amateur runners [ n = 16, age: 41.8 ± 13.5 (SD) yr, training: 93.8 ± 31.8 km/wk] compared with sedentary controls ( n = 9, age: 39.4 ± 10.2 yr). HPCs, plasma cortisol, interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), and the growth factor fms-like tyrosine kinase-3 (flt3)-ligand were measured at rest and after a marathon (M; n = 8) or half-marathon (HM; n = 8). Circulating HPC counts (i.e., CD34+cells and their subpopulations) were three- to fourfold higher in runners than in controls at baseline. They were unaffected by HM or M acutely but decreased the morning postrace. Baseline cortisol, flt3-ligand, IL-6, and G-CSF levels were similar in runners and controls. IL-6 and G-CSF increased to higher levels after M compared with HM, whereas cortisol and flt3-ligand increased similarly postrace. Our data suggest that increased HPCs reflect an adaptation response to recurrent, exercise-associated release of neutrophils and stress and inflammatory mediators, indicating modulation of bone marrow activity by habitual running.
130. The screening accuracy of the Edinburgh Postnatal Depression Scale (EPDS) to detect perinatal depression with and without the self-harm item in pregnant and postpartum women.
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Stefana A, Mirabella F, Gigantesco A, and Camoni L
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- Humans, Female, Pregnancy, Adult, Sensitivity and Specificity, Psychometrics instrumentation, Psychometrics standards, Pregnancy Complications diagnosis, Pregnancy Complications psychology, Postpartum Period psychology, Young Adult, Reproducibility of Results, Depression, Postpartum diagnosis, Self-Injurious Behavior diagnosis, Psychiatric Status Rating Scales standards
- Abstract
Background: This study aims to examine whether the Edinburgh Postnatal Depression Scale (EPDS), excluding the self-harm item (EPDS-9), performs as effectively as the full EPDS in identifying depression among perinatal women., Methods: A total of 3571 pregnant women and 3850 postpartum women participated in this observational study. Participants who scored ≥ 9 on the EPDS underwent further diagnostic evaluations by a clinical psychologist and/or psychiatrist., Results: The EPDS-9 and full EPDS demonstrated a near-perfect correlation in both the antepartum ( r = 0.996) and postpartum ( r = 0.998) cohorts. EPDS-9 showed exceptional precision in identifying depression as screened by the full EPDS at cutoff points ranging 9-14, with areas under the curve ≥0.998. The sensitivity of EPDS-9 and full EPDS to detect depression that requires psychotropic medications was poor. The highest accuracy for both versions was at a cutoff score of 9: sensitivity of 0.579 for the full EPDS and 0.526 for the EPDS-9. At the cutoff point of 9, EPDS-9 performed adequately in predicting the response of the participants to the self-harm item., Conclusion: The EPDS-9 represents a solid and effective replacement for the full EPDS in clinical settings. If the presence of suicidal thoughts needs to be assessed, specialized scales should be used.
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- 2024
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131. Multiscale modeling uncovers 7q11.23 copy number variation-dependent changes in ribosomal biogenesis and neuronal maturation and excitability.
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Mihailovich M, Germain PL, Shyti R, Pozzi D, Noberini R, Liu Y, Aprile D, Tenderini E, Troglio F, Trattaro S, Fabris S, Ciptasari U, Rigoli MT, Caporale N, D'Agostino G, Mirabella F, Vitriolo A, Capocefalo D, Skaros A, Franchini AV, Ricciardi S, Biunno I, Neri A, Nadif Kasri N, Bonaldi T, Aebersold R, Matteoli M, and Testa G
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- Humans, Ribosomes metabolism, Ribosomes genetics, Neurogenesis genetics, Williams Syndrome genetics, Williams Syndrome metabolism, Williams Syndrome pathology, Williams Syndrome physiopathology, Ribosomal Protein S6 metabolism, Ribosomal Protein S6 genetics, TOR Serine-Threonine Kinases metabolism, TOR Serine-Threonine Kinases genetics, Male, Cell Differentiation, Female, DNA Copy Number Variations, Neurons metabolism, Neurons pathology, Chromosomes, Human, Pair 7 genetics
- Abstract
Copy number variation (CNV) at 7q11.23 causes Williams-Beuren syndrome (WBS) and 7q microduplication syndrome (7Dup), neurodevelopmental disorders (NDDs) featuring intellectual disability accompanied by symmetrically opposite neurocognitive features. Although significant progress has been made in understanding the molecular mechanisms underlying 7q11.23-related pathophysiology, the propagation of CNV dosage across gene expression layers and their interplay remains elusive. Here we uncovered 7q11.23 dosage-dependent symmetrically opposite dynamics in neuronal differentiation and intrinsic excitability. By integrating transcriptomics, translatomics, and proteomics of patient-derived and isogenic induced neurons, we found that genes related to neuronal transmission follow 7q11.23 dosage and are transcriptionally controlled, while translational factors and ribosomal genes are posttranscriptionally buffered. Consistently, we found phosphorylated RPS6 (p-RPS6) downregulated in WBS and upregulated in 7Dup. Surprisingly, p-4EBP was changed in the opposite direction, reflecting dosage-specific changes in total 4EBP levels. This highlights different dosage-sensitive dyregulations of the mTOR pathway as well as distinct roles of p-RPS6 and p-4EBP during neurogenesis. Our work demonstrates the importance of multiscale disease modeling across molecular and functional layers, uncovers the pathophysiological relevance of ribosomal biogenesis in a paradigmatic pair of NDDs, and uncouples the roles of p-RPS6 and p-4EBP as mechanistically actionable relays in NDDs.
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- 2024
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132. The diagnostic accuracy of the Edinburgh Postnatal Depression Scale without the self-harm item: Does culture matter?
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Stefana A, Cena L, Trainini A, Palumbo G, Gigantesco A, and Mirabella F
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- Humans, Female, Adult, Culture, Psychiatric Status Rating Scales standards, Depression, Postpartum diagnosis, Self-Injurious Behavior diagnosis
- Abstract
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report.
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- 2024
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133. Screening for antenatal maternal depression: comparative performance of the Edinburgh Postnatal Depression Scale and Patient Health Questionnaire-9.
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Stefana A, Cena L, Trainini A, Palumbo G, Gigantesco A, and Mirabella F
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- Humans, Female, Pregnancy, Adult, Cross-Sectional Studies, Depression diagnosis, Patient Health Questionnaire, Psychiatric Status Rating Scales, Depression, Postpartum diagnosis, Depression, Postpartum psychology, Italy, Young Adult, Surveys and Questionnaires, Reproducibility of Results, Mass Screening methods, Pregnancy Complications psychology, Pregnancy Complications diagnosis, Psychometrics
- Abstract
Background: Maternal antenatal depression affects 21-28% of expectants globally and negatively impacts both maternal and child health in the short and long term., Objective: To compare the psychometric properties and clinical utility of the Edinburgh Postnatal Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ-9) in pregnant individuals., Methods: In this cross-sectional study, 953 third-trimester pregnant Italian individuals completed both the EPDS and the PHQ-9., Results: Both scales demonstrated good internal consistency (EPDS ω=0.83, PHQ-9 ω=0.80) and a moderate correlation between their scores (r=0.59). Concordance at recommended cut-off points (≥14 for both) was moderate (k=0.55). Factor analyses indicated a bifactor solution for the EPDS (dimensions: "depression" and "anxiety") and for the PHQ-9 (dimensions: "depression", "pregnancy symptoms", "somatic"). Benchmarks for clinical change were also established., Conclusions: The EPDS and PHQ-9 capture distinct aspects of perinatal depressive symptomatology. Clinically, these findings recommend using both scales in obstetric and gynaecologic settings to minimize false positives and negatives.
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- 2024
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134. Prevalence of anxiety and depression risk during the prepartum period in the different groups of women and responses from the Italian National Health Service.
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Smorti M, Mirabella F, Calamandrei G, Gigantesco A, Mauri G, Brescianini S, Aceti F, Adulti I, Bagolan P, Barbano G, Bellomo A, Cattaneo M, Cengia E, Fabiano A, Fent A, Ferraro L, Giacchetti N, Grimaldi Capitello T, Grillo A, LA Barbera D, Marcheggiani A, Mazza M, Messina L, Niolu C, Picciano G, Pistillo M, Regonesi M, Riolo R, Sani G, Triggiani A, Tomasello D, and Camoni L
- Abstract
Background: Specific screening for anxiety and depression in pregnant women is important to identify those at risk and to provide timely intervention. The aims of the study were: 1) to compare the risk of anxiety and depression in four groups of pregnant women belonging to four types of healthcare centers distinguished by the level of risk: at low-risk; at high-risk for an obstetric reason; at high-risk for fetal anomalies; at high-risk for psychiatric conditions and 2) to identify the response that the National Health Service offers to women positively screened for anxiety and depression., Methods: A cross-sectional study was conducted on 2801 pregnant women, cared for by National Health Service, divided into four groups: 1) low-risk pregnancy (N.=1970); 2) high-risk pregnancy for an obstetric reason (N.=218); 3) high-risk for fetal anomalies (N.=505); and 4) high-risk for psychiatric conditions (N.=108). Participants were screened using the Edinburgh Postnatal Depression Scale, the General Anxiety Disorder, and sociodemographic, anamnestic, and clinic questionnaires., Results: 28.9% of participants obtained an EPDS Score ≥9 and 17.1% a GAD-7 Score ≥8. The group at high-risk for fetal anomalies presented the highest prevalence of anxiety (29.3%) and depression (49.1%) while the group at low risk presented the lowest prevalence of anxiety (13%) and depression (24.6%). The groups at risk for obstetric reasons presented an intermediate prevalence. Psychiatric conditions constituted a higher risk for anxiety than depression. Counselling is recommended for about 70% of women at risk for anxiety and depression. Moreover, about 15% of women positive for screening were initiated into psychotherapy and about 1.5% into pharmacotherapy. 15% of women positive for screening were referred to other specialists., Conclusions: This study underlined the relevance of a prompt response by the National Health Service to mental health needs, especially in the risk conditions related to obstetric and/or fetal anomalies and psychopathology.
- Published
- 2023
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135. Comparing the factor structures and reliabilities of the EPDS and the PHQ-9 for screening antepartum and postpartum depression: a multigroup confirmatory factor analysis.
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Stefana A, Langfus JA, Palumbo G, Cena L, Trainini A, Gigantesco A, and Mirabella F
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- Female, Humans, Patient Health Questionnaire, Reproducibility of Results, Mass Screening, Psychiatric Status Rating Scales, Postpartum Period, Factor Analysis, Statistical, Depression diagnosis, Depression, Postpartum diagnosis
- Abstract
To evaluate and compare the factor structure and reliability of EPDS and PHQ in antepartum and postpartum samples. Parallel analysis and exploratory factor analysis were conducted to determine the structure of both scales in the entire sample as well as in the antepartum and postpartum groups. McDonald's omega statistics examined the utility of treating items as a single scale versus multiple factors. Multigroup confirmatory factor analysis (MCFA) was utilized to test the measurement invariance between the antepartum and postpartum groups. Two-factor models fit best for the EPDS in both the antepartum and postpartum groups; however, the most reliable score variance was attributable to a general factor for each scale. MCFA provided evidence of weak invariance across groups regarding factor loadings and partial invariance regarding item thresholds. PHQ-9 showed a two-factor model in the antepartum group; however, the same model did not fit well in the postpartum group. EPDS should be preferred to PHQ-9 for measuring depressive symptoms in peripartum populations. Both scales should be used as a single-factor scale. Caution is required when comparing the antepartum and postpartum scores., (© 2023. The Author(s).)
- Published
- 2023
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136. SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.
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Roshandel D, Sanders EJ, Shakeshaft A, Panjwani N, Lin F, Collingwood A, Hall A, Keenan K, Deneubourg C, Mirabella F, Topp S, Zarubova J, Thomas RH, Talvik I, Syvertsen M, Striano P, Smith AB, Selmer KK, Rubboli G, Orsini A, Ng CC, Møller RS, Lim KS, Hamandi K, Greenberg DA, Gesche J, Gardella E, Fong CY, Beier CP, Andrade DM, Jungbluth H, Richardson MP, Pastore A, Fanto M, Pal DK, and Strug LJ
- Abstract
Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10
-9 ) and 10p11.21 (P = 3.6 × 10-8 ). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3 ). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3 ) and increased seizure-like events (P = 6.8 × 10-7 ). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3 ). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease., (© 2023. Springer Nature Limited and Centre of Excellence in Genomic Medicine Research, King Abdulaziz University.)- Published
- 2023
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137. Maternal immune activation leads to defective brain blood vessels and intracerebral hemorrhages in male offspring.
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Rasile M, Lauranzano E, Faggiani E, Ravanelli MM, Colombo FS, Mirabella F, Corradini I, Malosio ML, Borreca A, Focchi E, Pozzi D, Giorgino T, Barajon I, and Matteoli M
- Published
- 2023
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138. Epidemiology of perinatal depression in Italy: systematic review and meta-analysis.
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Camoni L, Gigantesco A, Guzzini G, Pellegrini E, and Mirabella F
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- Pregnancy, Female, Humans, Depression epidemiology, Prevalence, Italy epidemiology, Psychiatric Status Rating Scales, Depression, Postpartum epidemiology, Depressive Disorder epidemiology
- Abstract
Introduction: This review aims to synthesise the studies that have estimated the prevalence of perinatal depression in Italy, summarising the results of the existing literature based on their quality., Materials and Methods: Systematic searches were conducted in four major databases, and a random effect meta-analysis was performed to achieve the pooled variance of perinatal depression., Results: The pooled prepartum risk of depression prevalence was 20.2% (CI 95% 15.3-24.5) while the postpartum risk of depression prevalence was 27.5% (CI 95% 17.8-37.3) for an Edinburgh Postnatal Depression Scale (EPDS) cut-off score ≥9 and 11.1% (CI 95% 6.0-16.2) for an EPDS cut-off score ≥12. Significant publication bias was found and was determined by the presence of a small study with a low prevalence and a large study with a high prevalence., Conclusion: The prevalence of perinatal risk of depression is similar to that reported in other countries. The high prevalence of prepartum risk suggests the need to activate specific prevention actions during this period.
- Published
- 2023
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139. Graphene-on-gold surface plasmon resonance sensors resilient to high-temperature annealing.
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Jungnickel R, Mirabella F, Stockmann JM, Radnik J, and Balasubramanian K
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- Temperature, Gold chemistry, Adsorption, Surface Plasmon Resonance, Graphite chemistry
- Abstract
Gold films coated with a graphene sheet are being widely used as sensors for the detection of label-free binding interactions using surface plasmon resonance (SPR). During the preparation of such sensors, it is often essential to subject the sensor chips to a high-temperature treatment in order to ensure a clean graphene surface. However, sensor chips used currently, which often use chromium as an adhesion promoter, cannot be subjected to temperatures above 250 °C, because under such conditions, chromium is found to reorganize and diffuse to the surface, where it is easily oxidized, impairing the quality of SPR spectra. Here we present an optimized preparation strategy involving a three-cycle tempering coupled with chromium (oxide) etching, which allows the graphene-coated SPR chips to be annealed up to 500 °C with little deterioration of the surface morphology. In addition, the treatment delivers a surface that shows a clear enhancement in spectral response together with a good refractive index sensitivity. We demonstrate the applicability of our sensors by studying the kinetics of avidin-biotin binding at different pH repeatedly on the same chip. The possibility to anneal can be exploited to recover the original surface after sensing trials, which allowed us to reuse the sensor for at least six cycles of biomolecule adsorption., (© 2022. The Author(s).)
- Published
- 2023
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140. Reaction of the carbonate Sibillini Mountains Basal aquifer (Central Italy) to the extensional 2016-2017 seismic sequence.
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Cambi C, Mirabella F, Petitta M, Banzato F, Beddini G, Cardellini C, Fronzi D, Mastrorillo L, Tazioli A, and Valigi D
- Abstract
Hydrogeological perturbations in response to earthquakes are widely described worldwide. In carbonate aquifers, a post-seismic discharge increase is often attributed to an increase of bulk permeability due to co-seismic fracturing and the attention on the role of faults to explain the diversion of groundwater is increasing. We focus on the reaction of carbonate hydrogeological basins to extensional seismicity, taking as an example the effects of the Central Italy 2016-2017 seismic sequence, on the Basal aquifer of the Sibillini Mountains area. Geo-structural, seismological and ground deformation data were collected and merged with artificial tracer tests results and with a 4-years discharge and geochemical monitoring campaign. The main NNW-directed groundwater flow was diverted to the west and a discharge deficit was observed at the foot-wall of the activated fault system with a relevant discharge increase, accompanied by geochemical variations, at the fault system hanging-wall. The observed variations are consistent with the combined action of a permeability increase along the activated fault systems, which modified the predominant pre-seismic along-strike regional flow, and with hydraulic conductivity increase due to fracturing, determining a fast aquifers emptying. We show that the prevailing mechanism depends on the aquifer systems position with respect to the activated faults., (© 2022. The Author(s).)
- Published
- 2022
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141. Water Structures Reveal Local Hydrophobicity on the In 2 O 3 (111) Surface.
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Chen H, Blatnik MA, Ritterhoff CL, Sokolović I, Mirabella F, Franceschi G, Riva M, Schmid M, Čechal J, Meyer B, Diebold U, and Wagner M
- Abstract
Clean oxide surfaces are generally hydrophilic. Water molecules anchor at undercoordinated surface metal atoms that act as Lewis acid sites, and they are stabilized by H bonds to undercoordinated surface oxygens. The large unit cell of In
2 O3 (111) provides surface atoms in various configurations, which leads to chemical heterogeneity and a local deviation from this general rule. Experiments (TPD, XPS, nc-AFM) agree quantitatively with DFT calculations and show a series of distinct phases. The first three water molecules dissociate at one specific area of the unit cell and desorb above room temperature. The next three adsorb as molecules in the adjacent region. Three more water molecules rearrange this structure and an additional nine pile up above the OH groups. Despite offering undercoordinated In and O sites, the rest of the unit cell is unfavorable for adsorption and remains water-free. The first water layer thus shows ordering into nanoscopic 3D water clusters separated by hydrophobic pockets.- Published
- 2022
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142. Maternal immune activation leads to defective brain-blood vessels and intracerebral hemorrhages in male offspring.
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Rasile M, Lauranzano E, Faggiani E, Ravanelli MM, Colombo FS, Mirabella F, Corradini I, Malosio ML, Borreca A, Focchi E, Pozzi D, Giorgino T, Barajon I, and Matteoli M
- Subjects
- Animals, Female, Male, Mice, Pregnancy, Behavior, Animal, Brain blood supply, Brain pathology, Disease Models, Animal, Endothelial Cells metabolism, Poly I-C adverse effects, Transforming Growth Factor beta1 metabolism, Cerebral Hemorrhage pathology, Prenatal Exposure Delayed Effects pathology
- Abstract
Intracerebral hemorrhages are recognized risk factors for neurodevelopmental disorders and represent early biomarkers for cognitive dysfunction and mental disability, but the pathways leading to their occurrence are not well defined. We report that a single intrauterine exposure of the immunostimulant Poly I:C to pregnant mice at gestational day 9, which models a prenatal viral infection and the consequent maternal immune activation, induces the defective formation of brain vessels and causes intracerebral hemorrhagic events, specifically in male offspring. We demonstrate that maternal immune activation promotes the production of the TGF-β1 active form and the consequent enhancement of pSMAD1-5 in males' brain endothelial cells. TGF-β1, in combination with IL-1β, reduces the endothelial expression of CD146 and claudin-5, alters the endothelium-pericyte interplay resulting in low pericyte coverage, and increases hemorrhagic events in the adult offspring. By showing that exposure to Poly I:C at the beginning of fetal cerebral angiogenesis results in sex-specific alterations of brain vessels, we provide a mechanistic framework for the association between intragravidic infections and anomalies of the neural vasculature, which may contribute to neuropsychiatric disorders., (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
- Published
- 2022
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143. The Impact of the COVID-19 Pandemic on Women's Perinatal Mental Health: Preliminary Data on the Risk of Perinatal Depression/Anxiety from a National Survey in Italy.
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Camoni L, Mirabella F, Gigantesco A, Brescianini S, Ferri M, Palumbo G, Calamandrei G, and On Behalf Of The Perinatal Mental Health Network
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- Humans, Female, Pregnancy, Adolescent, Young Adult, Adult, Middle Aged, Prospective Studies, Depression epidemiology, Mental Health, Retrospective Studies, Preliminary Data, SARS-CoV-2, Anxiety Disorders epidemiology, Anxiety epidemiology, Anxiety diagnosis, Pandemics, COVID-19 epidemiology
- Abstract
Increasing evidence suggests that during the COVID-19 pandemic, anxiety and depression during the perinatal period increased. The aim of the study is to estimate the prevalence of risk for both maternal depression and anxiety among women attending 18 healthcare centres in Italy during the SARS-COV-2 pandemic and to investigate the psychosocial risks and protective factors associated. It was divided into a retrospective phase (2019, 2020, and the first nine months of 2021) and a prospective phase (which began in November 2021 and it is still ongoing), which screened 12,479 and 2349 women, respectively, for a total of 14,828 women in the perinatal period. To evaluate the risk of anxiety and depression, the General Anxiety Disorder-7 (GAD-7), the Edinburgh Postnatal Depression Scale (EPDS), and an ad hoc form were used to collect sociodemographic variables. In the prospective study, the average age of the women is 31 (range 18-52) years. Results showed that the percentage of women who had EPDS score ≥9 increased from 11.6% in 2019 to 25.5% in the period ranging from November 2021 to April 2022. In logistic regression models, the variables associated with the risk of depression at a level ≤0.01 include having economic problems (OR 2.16) and not being able to rely on support from relatives or friends (OR 2.36). Having the professional status of the housewife is a lower risk (OR 0.52). Those associated with the risk of anxiety include being Italian (OR 2.97), having an education below secondary school level (OR 0.47), having some or many economic problems (OR 2.87), being unable to rely on support from relatives or friends (OR 2.48), and not having attended an antenatal course (OR 1.41). The data from this survey could be useful to determine the impact of the SARS-COV-2 pandemic on women and to establish a screening program with common and uniformly applied criteria which are consistent with national and international women's mental health programs.
- Published
- 2022
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144. A Brief Depression Screening Tool for Perinatal Clinical Practice: The Performance of the PHQ-2 Compared with the PHQ-9.
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Gigantesco A, Palumbo G, Cena L, Camoni L, Trainini A, Stefana A, and Mirabella F
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- Female, Humans, Mass Screening, Postpartum Period, Pregnancy, Sensitivity and Specificity, Surveys and Questionnaires, Depression diagnosis, Patient Health Questionnaire
- Abstract
Introduction: There is ongoing interest in using brief screening instruments to identify perinatal depression in clinical practice. One ultra-brief screening instrument for depression is the Patient Health Questionnaire-2 (PHQ-2), but thus far its accuracy in perinatal clinical practice has been barely researched. In the present study, we aimed to assess the screening accuracy of the PHQ-2 against the Patient Health Questionnaire-9 (PHQ-9) in a large sample of perinatal women., Methods: A total of 1155 consecutive women attending 11 health care centers throughout Italy completed the PHQ-9 (which includes the PHQ-2) during pregnancy (27-40 weeks) or postpartum (1-13 weeks). Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio positive, likelihood ratio negative, and overall accuracy were calculated using cut points 3 or greater and 2 or greater., Results: During pregnancy, PHQ-2 greater than or equal to 3 revealed low sensitivity (38.4%-44.7%) but high specificity (97.8%-99.3%). In postpartum, it revealed moderate sensitivity (56.9%-70.6%), high specificity (95.8%-99.8%), and fair overall accuracy in pregnancy (70%). The alternative threshold greater than or equal to 2 revealed very high sensitivity (pregnancy: 92.1%-95.2%; postpartum: 87.1%-95.2%), moderate specificity (pregnancy: 78.1%-83.2%; postpartum: 68.8%-81.1%) and good overall accuracy, both during pregnancy (87%) and postpartum (84%)., Discussion: The PHQ-2 provided acceptable accuracy for screening for depression compared with the PHQ-9. In perinatal screening practice, a threshold of 2 or greater should be preferred as this ensures high sensitivity, missing only approximately 6% to 8% of cases, and a false-positive rate (percentage of women classified as affected with depressive symptoms when they are not) of 19% to 25%., (© 2022 by the American College of Nurse-Midwives.)
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- 2022
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145. Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies.
- Author
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Rasile M, Lauranzano E, Mirabella F, and Matteoli M
- Subjects
- Animals, Brain, Female, Humans, Pregnancy, COVID-19, Mental Disorders, Pregnancy Complications, Infectious, Prenatal Exposure Delayed Effects
- Abstract
Intragravidic and perinatal infections, acting through either direct viral effect or immune-mediated responses, are recognized causes of liability for neurodevelopmental disorders in the progeny. The large amounts of epidemiological data and the wealth of information deriving from animal models of gestational infections have contributed to delineate, in the last years, possible underpinning mechanisms for this phenomenon, including defects in neuronal migration, impaired spine and synaptic development, and altered activation of microglia. Recently, dysfunctions of the neurovascular unit and anomalies of the brain vasculature have unexpectedly emerged as potential causes at the origin of behavioral abnormalities and psychiatric disorders consequent to prenatal and perinatal infections. This review aims to discuss the up-to-date literature evidence pointing to the neurovascular unit and brain vasculature damages as the etiological mechanisms in neurodevelopmental syndromes. We focus on the inflammatory events consequent to intragravidic viral infections as well as on the direct viral effects as the potential primary triggers. These authors hope that a timely review of the literature will help to envision promising research directions, also relevant for the present and future COVID-19 longitudinal studies., (© 2021 Federation of European Biochemical Societies.)
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- 2022
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146. Poor social support is associated with preterm birth rather than maternal prenatal anxiety and depression: a retrospective case-control study.
- Author
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Cena L, Mirabella F, Palumbo G, Gigantesco A, Camoni L, Trainini A, and Stefana A
- Subjects
- Anxiety, Case-Control Studies, Depression, Female, Humans, Infant, Newborn, Pregnancy, Retrospective Studies, Social Support, Premature Birth
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- 2022
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147. PSYChosomatic Medicine in ONcologIc and Cardiac Disease (PSYCHONIC) Study-A Retrospective and Prospective Observational Research Protocol.
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Roncella A, Pristipino C, Di Carlo O, Ansuini M, Corbosiero A, Di Fusco SA, Palumbo G, Gigantesco A, Mirabella F, De Angelis R, Pasceri V, Cancellara L, Colivicchi F, Allan R, Mirri MA, and Speciale G
- Abstract
Psychosocial factors play an important role in non-communicable diseases (NCDs). This observational study is primarily aimed at assessing the relationship of psychological characteristics of patients with the outcomes of different NCDs, and to assess short-term psychotherapy (STP) efficacy in the real world. Methods : One hundred and forty patients with recent acute myocardial infarction, Takotsubo syndrome, or non-metastatic breast cancer and a control group of 140 age and sex-matched healthy subjects, will be enrolled. All subjects will be administered psychometric tests, quality of life tests, a specific body perception questionnaire, a dream questionnaire, and a projective test, the Six Drawing test at baseline and follow-up. All subjects with medical conditions will be asked to freely choose between an ontopsychological STP along with standard medical therapy and, whenever indicated, rehabilitation therapy or medical therapy plus rehabilitation alone. The study endpoints will be to evaluate: the relationship of the psychological characteristics of enrolled subjects with the outcomes of different NCDs, predictors of the choice of psychotherapy, and the efficacy of ontopsychological intervention on psychological and medical outcomes. Conclusion : This study will generate data on distinctive psychological characteristics of patients suffering from different CDs and their relationship with medical outcomes, as well as explore the efficacy of ontopsychological STP in these patients in the real world. (Number of registration: NCT03437642).
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- 2021
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148. Prevalence of comorbid anxiety and depressive symptomatology in the third trimester of pregnancy: Analysing its association with sociodemographic, obstetric, and mental health features.
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Cena L, Gigantesco A, Mirabella F, Palumbo G, Camoni L, Trainini A, and Stefana A
- Subjects
- Adult, Anxiety epidemiology, Cross-Sectional Studies, Depression, Female, Humans, Pregnancy, Pregnancy Trimester, Third, Prevalence, Risk Factors, Surveys and Questionnaires, Mental Health, Pregnancy Complications epidemiology
- Abstract
Background: Little is known about the prevalence of comorbid anxiety and depression (CAD) during pregnancy and its risk factors. The aims of this study are to determine the prevalence of CAD in the third trimester of pregnancy and analyse its association with socio-demographic, obstetric, and mental health features., Methods: In a sample of 934 Italian pregnant women, CAD was defined as having (1) a score of ≥ 10 on the EPDS - depression subscale and/or on the PHQ-9, and (2) a score of ≥ 40 on the State-Trait Anxiety Inventory State and/or a score of ≥ 6 on the EPDS - anxiety subscale. Logistic regression analyses were used to identify socio-demographic, obstetrics, and mental health risk factors of CAD., Results: The prevalence of CAD was 6.8%. Age between 30 and 35 years (OR=3.01, 95% CI: 1.22-7.45) compared to younger age, current sleep disorders (OR=7.88, 95% CI: 3.83-16.23), and preconception mood disorders (OR=2.76, 95% CI: 1.31-5.84) were associated with higher odds of CAD. Conversely, the presence of no or few economic problems (OR=0.21, 95% CI: 0.07-0.65; OR=0.26, 95% CI: 0.09-0.77) and the perception of enough or more than enough practical support from friends or relatives (OR=0.32, 95% CI: 0.13-0.80; OR=0.22, 95% CI: 0.09-0.53) were associated with lower odds of developing CAD., Limitations: The cross-sectional design; the use of self-report questionnaires., Conclusion: CAD is relatively common among third-trimester antepartum women. The provision of economic/practical support may reduce CAD prevalence and its direct and indirect costs., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2021
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149. The limited screening accuracy of the Patient Health Questionnaire-2 in detecting depression among perinatal women in Italy.
- Author
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Gigantesco A, Palumbo G, Cena L, Camoni L, Trainini A, Stefana A, and Mirabella F
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- Adolescent, Adult, Depression epidemiology, Depression, Postpartum epidemiology, Female, Humans, Italy epidemiology, Mass Screening, Patient Health Questionnaire, Perinatal Care, Postpartum Period, Predictive Value of Tests, Pregnancy, Pregnancy Complications epidemiology, Prognosis, Young Adult, Depression diagnosis, Depression, Postpartum diagnosis, Pregnancy Complications diagnosis
- Abstract
Background: The PHQ-2 was recently recommended by the International Consortium for Health Outcomes Measurement as a form of initial perinatal screening, followed by the EPDS only for women with positive PHQ-2 score. However, the accuracy of the PHQ-2 in perinatal clinical practice has been barely researched, to date. In the present study, we aim to assess the accuracy of the PHQ-2 against the EPDS in a large sample of perinatal women., Methods: A total of 1155 consecutive women attending eleven primary or secondary health care centres throughout Italy completed the EPDS and the PHQ-2 during pregnancy (27-40-weeks) or postpartum (1-13-weeks). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio, post-test probabilities and area under the curve (AUC) of the PHQ-2, using a cut-off of ≥ 3, were calculated., Main Findings: During pregnancy, PHQ-2 revealed low sensitivity (39.5%) and PPV (39.4%) but high specificity and NPV (97.5%). In postpartum, it revealed very low sensitivity (32.7%) and moderately high NPV (80.9%), but high specificity (99.3%) and PPV (94.4%). Given the low sensitivity despite the high specificity, the PHQ-2 demonstrated poor accuracy (AUC from 0.66 to 0.68)., Conclusion: Initial screening by means of PHQ-2 failed to identify an acceptable number of perinatal women at-risk of depression in Italian clinical practice. The PHQ-2 performance suggested that it has insufficient sensitivity and discriminatory power, and may be inadequate as a screening tool for maternal depression., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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150. Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring.
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Mirabella F, Desiato G, Mancinelli S, Fossati G, Rasile M, Morini R, Markicevic M, Grimm C, Amegandjin C, Termanini A, Peano C, Kunderfranco P, di Cristo G, Zerbi V, Menna E, Lodato S, Matteoli M, and Pozzi D
- Subjects
- Animals, Cytokines biosynthesis, Disease Models, Animal, Disease Susceptibility, Female, Hippocampus physiopathology, Inflammation Mediators metabolism, Mice, Pregnancy, Signal Transduction, Synaptic Transmission, Hippocampus metabolism, Interleukin-6 biosynthesis, Maternal Exposure, Neurons metabolism, Prenatal Exposure Delayed Effects, Synapses metabolism
- Abstract
Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
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