Colombo Dott.ssa Giulia

Pubblicazioni su PubMed

• The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica).
  Mol Biol Evol

  2022 Jun;39(6):. doi: msac113.
  
  Lombardo Gianluca, Rambaldi Migliore Nicola, Colombo Giulia, Capodiferro Marco Rosario, Formenti Giulio, Caprioli Manuela, Moroni Elisabetta, Caporali Leonardo, Lancioni Hovirag, Secomandi Simona, Gallo Guido Roberto, Costanzo Alessandra, Romano Andrea, Garofalo Maria, Cereda Cristina, Carelli Valerio, Gillespie Lauren, Liu Yang, Kiat Yosef, Marzal Alfonso, López-Calderón Cosme, Balbontín Javier, Mousseau Timothy A, Matyjasiak Piotr, Møller Anders Pape, Semino Ornella, Ambrosini Roberto, Bonisoli-Alquati Andrea, Rubolini Diego, Ferretti Luca, Achilli Alessandro, Gianfranceschi Luca, Olivieri Anna, Torroni Antonio
  
  Abstract
  
  The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51?kya, into the Americas, from where a relatively recent (
  © The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.
  
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• The ?2 nicotinic subunit linked to sleep-related epilepsy differently affects fast-spiking and regular spiking somatostatin-expressing neurons in murine prefrontal cortex.
  Prog Neurobiol

  2022 07;214():102279. doi: S0301-0082(22)00065-X.
  
  Meneghini Simone, Modena Debora, Colombo Giulia, Coatti Aurora, Milani Niccolò, Madaschi Laura, Amadeo Alida, Becchetti Andrea
  
  Abstract
  
  Mutant subunits of the neuronal nicotinic ACh receptor (nAChR) can cause Autosomal Dominant Sleep-related Hypermotor Epilepsy (ADSHE), characterized by frontal seizures during non-rapid eye movement (NREM) sleep. We studied the cellular bases of the pathogenesis in brain slices from mice conditionally expressing the ADSHE-linked ?2 nAChR subunit. ?2 mice displayed minor structural alterations, except for a ~10% decrease of prefrontal cortex thickness. However, they showed a substantial decrease of the excitatory input to layer V fast-spiking (FS) interneurons, despite a concomitant increase in the number of glutamatergic terminals around the cell soma. Hence, prefrontal hyperexcitability may depend on a permanent impairment of surround inhibition. The effect disappeared when ?2 was silenced until postnatal day 15th, suggesting that the transgene selectively affects the maturation of glutamatergic synapses on FS neurons. The other main population of interneurons in layer V was constituted by somatostatin-expressing regular spiking cells. When tested with 10 µM nicotine, these displayed larger somatic nicotinic currents in transgenic mice. Thus, during wakefulness, activation of ?2-containing nAChRs by the high cholinergic tone may counteract hyperexcitability by promoting local inhibition by somatostatin-expressing cells and decreasing the effect of glutamatergic deficit in FS neurons. This interpretation was tested in networks disinhibited by 2 ?M bicuculline. Slices expressing ?2 were more susceptible to develop synchronized activity in the absence of nicotine. Addition of the drug boosted excitability in the controls, but had little effect in ?2. Our findings suggest why NREM sleep favors ADSHE seizures and nicotine can be palliative in patients.
  
  Copyright © 2022 Elsevier Ltd. All rights reserved.
  
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• Overview of the Americas' First Peopling from a Patrilineal Perspective: New Evidence from the Southern Continent.
  Genes (Basel)

  2022 01;13(2):. doi: 220.
  
  Colombo Giulia, Traverso Luca, Mazzocchi Lucia, Grugni Viola, Rambaldi Migliore Nicola, Capodiferro Marco Rosario, Lombardo Gianluca, Flores Rodrigo, Karmin Monika, Rootsi Siiri, Ferretti Luca, Olivieri Anna, Torroni Antonio, Martiniano Rui, Achilli Alessandro, Raveane Alessandro, Semino Ornella
  
  Abstract
  
  Uniparental genetic systems are unique sex indicators and complement the study of autosomal diversity by providing landmarks of human migrations that repeatedly shaped the structure of extant populations. Our knowledge of the variation of the male-specific region of the Y chromosome in Native Americans is still rather scarce and scattered, but by merging sequence information from modern and ancient individuals, we here provide a comprehensive and updated phylogeny of the distinctive Native American branches of haplogroups C and Q. Our analyses confirm C-MPB373, C-P39, Q-Z780, Q-M848, and Q-Y4276 as the main founding haplogroups and identify traces of unsuccessful (pre-Q-F1096) or extinct (C-L1373*, Q-YP4010*) Y-chromosome lineages, indicating that haplogroup diversity of the founder populations that first entered the Americas was greater than that observed in the Indigenous component of modern populations. In addition, through a diachronic and phylogeographic dissection of newly identified Q-M848 branches, we provide the first Y-chromosome insights into the early peopling of the South American hinterland (Q-BY104773 and Q-BY15730) and on overlying inland migrations (Q-BY139813).
  
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• Weaving Mitochondrial DNA and Y-Chromosome Variation in the Panamanian Genetic Canvas.
  Genes (Basel)

  2021 11;12(12):. doi: 1921.
  
  Rambaldi Migliore Nicola, Colombo Giulia, Capodiferro Marco Rosario, Mazzocchi Lucia, Chero Osorio Ana Maria, Raveane Alessandro, Tribaldos Maribel, Perego Ugo Alessandro, Mendizábal Tomás, Montón Alejandro García, Lombardo Gianluca, Grugni Viola, Garofalo Maria, Ferretti Luca, Cereda Cristina, Gagliardi Stella, Cooke Richard, Smith-Guzmán Nicole, Olivieri Anna, Aram Bethany, Torroni Antonio, Motta Jorge, Semino Ornella, Achilli Alessandro
  
  Abstract
  
  The Isthmus of Panama was a crossroads between North and South America during the continent's first peopling (and subsequent movements) also playing a pivotal role during European colonization and the African slave trade. Previous analyses of uniparental systems revealed significant sex biases in the genetic history of Panamanians, as testified by the high proportions of Indigenous and sub-Saharan mitochondrial DNAs (mtDNAs) and by the prevalence of Western European/northern African Y chromosomes. Those studies were conducted on the general population without considering any self-reported ethnic affiliations. Here, we compared the mtDNA and Y-chromosome lineages of a new sample collection from 431 individuals (301 males and 130 females) belonging to either the general population, mixed groups, or one of five Indigenous groups currently living in Panama. We found different proportions of paternal and maternal lineages in the Indigenous groups testifying to pre-contact demographic events and genetic inputs (some dated to Pleistocene times) that created genetic structure. Then, while the local mitochondrial gene pool was marginally involved in post-contact admixtures, the Indigenous Y chromosomes were differentially replaced, mostly by lineages of western Eurasian origin. Finally, our new estimates of the sub-Saharan contribution, on a more accurately defined general population, reduce an apparent divergence between genetic and historical data.
  
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• Sources and clinical significance of aspartate aminotransferase increases in COVID-19.
  Clin Chim Acta

  2021 Nov;522():88-95. doi: S0009-8981(21)00290-4.
  
  Aloisio Elena, Colombo Giulia, Arrigo Claudia, Dolci Alberto, Panteghini Mauro
  
  Abstract
  
  BACKGROUND:
  Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk.
  
  METHODS:
  2054 hospitalized COVID-19 patients were studied. To identify sources of AST release, correlations between AST peak values and other biomarkers of tissue damage, i.e., alanine aminotransferase (ALT) for hepatocellular damage, creatine kinase (CK) for muscle damage, lactate dehydrogenase for multiorgan involvement, alkaline phosphatase and ?-glutamyltransferase for cholestatic injury, and C-reactive protein (CRP) for systemic inflammation, were performed and coefficients of determination estimated. The role of AST to predict death and intensive care unit admission during hospitalization was also evaluated. All measurements were performed using standardized assays.
  
  RESULTS:
  AST was increased in 69% of patients. Increases could be fully explained by summing the effects of hepatocellular injury [AST dependence from ALT, 66.8% [95% confidence interval (CI): 64.5-69.1)] and muscle damage [AST dependence from CK, 42.6% (CI: 39.3-45.8)]. We were unable to demonstrate an independent association of AST increases with worse outcomes.
  
  CONCLUSION:
  The mechanisms for abnormal AST in COVID-19 are likely multifactorial and a status related to tissue suffering could play a significant role. The clinical significance of AST elevations remains unclear.
  
  Copyright © 2021 Elsevier B.V. All rights reserved.
  
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• Early evidence of SARS-CoV-2 in Milan, Jan-Feb 2020.
  Ital J Pediatr

  2021 Jun;47(1):145. doi: 10.1186/s13052-021-01095-4.
  
  Milani Gregorio P, Casazza Giovanni, Corsello Antonio, Marchisio Paola, Rocchi Alessia, Colombo Giulia, Agostoni Carlo, Costantino Giorgio
  
  Abstract
  
  BACKGROUND:
  A few studies have suggested that the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was present in Northern Italy several weeks before its official detection on February 21, 2020. On the other hand, no clinical data have been provided so far to support such hypothesis. We investigated clinical-epidemiological evidence of SARS-CoV-2 infection among children and adults referring to emergency department (ED) in the main hospital of the center of Milan (Italy) before February 21, 2020.
  
  METHODS:
  A retrospective analysis of medical records of ED visits at the Fondazione Ca' Granda Policlinico, Milan between January 11 and February 15 in 2017, 2018, 2019 and in 2020 was performed. The number of subjects referring with fever, cough or dyspnea was compared between the studied period of 2020 and the previous 3 years, by calculating a standardized referral ratio (SRR, number of observed cases in 2020 divided by the number of expected cases according to 2017-2019) and the corresponding 95% confidence interval (CI).
  
  RESULTS:
  In the pediatric ED, 7709 (average 2570/year) and 2736 patients were visited during the period 2017-2019 and in the 2020, respectively. Among adults, 13,465 (average 4488/year) and 4787 were visited during the period 2017-2019 and in the 2020, respectively. The SRR was 1.16 (95% CI 1.10-1.23) in children and 1.25 (95% CI 1.16-1.35) in adults. The ratio for the two (children and adults) SRRs was 0.93 (0.84-1.02), suggesting a trend towards a higher frequency in adults compared to children.
  
  CONCLUSIONS:
  This study suggests that SARS-CoV-2 might have spread in Milan before February 21, 2020 with a minor trend among children.
  
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• Archaeogenomic distinctiveness of the Isthmo-Colombian area.
  Cell

  2021 04;184(7):1706-1723.e24. doi: S0092-8674(21)00229-4.
  
  Capodiferro Marco Rosario, Aram Bethany, Raveane Alessandro, Rambaldi Migliore Nicola, Colombo Giulia, Ongaro Linda, Rivera Javier, Mendizábal Tomás, Hernández-Mora Iosvany, Tribaldos Maribel, Perego Ugo Alessandro, Li Hongjie, Scheib Christiana Lyn, Modi Alessandra, Gòmez-Carballa Alberto, Grugni Viola, Lombardo Gianluca, Hellenthal Garrett, Pascale Juan Miguel, Bertolini Francesco, Grieco Gaetano Salvatore, Cereda Cristina, Lari Martina, Caramelli David, Pagani Luca, Metspalu Mait, Friedrich Ronny, Knipper Corina, Olivieri Anna, Salas Antonio, Cooke Richard, Montinaro Francesco, Motta Jorge, Torroni Antonio, Martín Juan Guillermo, Semino Ornella, Malhi Ripan Singh, Achilli Alessandro
  
  Abstract
  
  The recently enriched genomic history of Indigenous groups in the Americas is still meager concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic events contributed to the extensive genetic structure currently seen in the area, which is also characterized by a distinctive Isthmo-Colombian Indigenous component. This component drives these populations on a specific variability axis and derives from the local admixture of different ancestries of northern North American origin(s). Two of these ancestries were differentially associated to Pleistocene Indigenous groups that also moved into South America, leaving heterogenous genetic footprints. An additional Pleistocene ancestry was brought by a still unsampled population of the Isthmus (UPopI) that remained restricted to the Isthmian area, expanded locally during the early Holocene, and left genomic traces up to the present day.
  
  Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
  
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• Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology.
  Brain Sci

  2020 Nov;10(12):. doi: E907.
  
  Becchetti Andrea, Grandi Laura Clara, Colombo Giulia, Meneghini Simone, Amadeo Alida
  
  Abstract
  
  Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na-gated K channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns ?4 and ?2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant ?2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of ?2-containing (?2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have different effects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.
  
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• Clinical and pharmacological characteristics of elderly patients admitted for bleeding: impact on in-hospital mortality.
  Ann Med

  2020 11;52(7):413-422. doi: 10.1080/07853890.2020.1808238.
  
  Pani Arianna, Pastori Daniele, Senatore Michele, Romandini Alessandra, Colombo Giulia, Agnelli Francesca, Scaglione Francesco, Colombo Fabrizio
  
  Abstract
  
  INTRODUCTION:
  Clinical and pharmacological characteristics of elderly patients hospitalized for bleeding and in-hospital mortality according to bleeding type are barely described.
  
  METHODS:
  Retrospective cohort study of 13,496 consecutive patients admitted to internal medicine wards. Clinical characteristics, comorbidities and pharmacological treatments were collected for each patient. Predictors of in-hospital mortality were investigated.
  
  RESULTS:
  Overall, 531 (3.9%) patients were admitted for bleeding: 189 clinically relevant non-major bleeding, 106 cerebral and 236 major non-cerebral (95.8% gastrointestinal (GI)). Among 106 cerebral bleedings, 28.3% and 24.5% were typical and atypical intracranial, respectively, and 47.2% were subdural haemorrhages. Most of patients with GI bleeding presented with anaemia (90.7%). A similar rate of GI bleeding was found in aspirin-treated patients taking or not proton pump inhibitors (PPI). In-hospital mortality was 9.98%. Age ?80 years (odds ratio (OR) 2.513, =.005), cerebral bleeding (OR 5.373, <.001 egfr and copd were positively associated with mortality while ace inhibitors use was negatively>
  CONCLUSIONS:
  The most frequent type of major haemorrhage was GI bleeding, which was not modified by the use of PPI in patients taking aspirin. Cerebral bleeding increased all-cause death, which was lower in ACE inhibitors/ARBs users. KEY MESSAGE Gastrointestinal (GI) bleeding was the most common reason for hospital admission. The rate of GI bleeding was similar in patients on aspirin using or not PPI. Cerebral bleeding increased in-hospital mortality, which was lower in patients taking ACE inhibitors/ARBs.
  
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• Adult-Onset Still Disease After Human Herpesvirus 6 Infection in an Elderly Patient: A Case Report.
  J Clin Rheumatol

  2021 Dec;27(8S):S466-S468. doi: 10.1097/RHU.0000000000001225.
  
  Rossio Raffaella, Colombo Giulia, Piconi Stefania, Peyvandi Flora
  
  
  
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• Y-chromosome and Surname Analyses for Reconstructing Past Population Structures: The Sardinian Population as a Test Case.
  Int J Mol Sci

  2019 Nov;20(22):. doi: E5763.
  
  Grugni Viola, Raveane Alessandro, Colombo Giulia, Nici Carmen, Crobu Francesca, Ongaro Linda, Battaglia Vincenza, Sanna Daria, Al-Zahery Nadia, Fiorani Ornella, Lisa Antonella, Ferretti Luca, Achilli Alessandro, Olivieri Anna, Francalacci Paolo, Piazza Alberto, Torroni Antonio, Semino Ornella
  
  Abstract
  
  Many anthropological, linguistic, genetic and genomic analyses have been carried out to evaluate the potential impact that evolutionary forces had in shaping the present-day Sardinian gene pool, the main outlier in the genetic landscape of Europe. However, due to the homogenizing effect of internal movements, which have intensified over the past fifty years, only partial information has been obtained about the main demographic events. To overcome this limitation, we analyzed the male-specific region of the Y chromosome in three population samples obtained by reallocating a large number of Sardinian subjects to the place of origin of their monophyletic surnames, which are paternally transmitted through generations in most of the populations, much like the Y chromosome. Three Y-chromosome founding lineages, G2-L91, I2-M26 and R1b-V88, were identified as strongly contributing to the definition of the outlying position of Sardinians in the European genetic context and marking a significant differentiation within the island. The present distribution of these lineages does not always mirror that detected in ancient DNAs. Our results show that the analysis of the Y-chromosome gene pool coupled with a sampling method based on the origin of the family name, is an efficient approach to unravelling past heterogeneity, often hidden by recent movements, in the gene pool of modern populations. Furthermore, the reconstruction and comparison of past genetic isolates represent a starting point to better assess the genetic information deriving from the increasing number of available ancient DNA samples.
  
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• Combined leadless pacemaker and subcutaneous implantable cardioverter-defibrillator to manage recurrent transvenous system failures.
  J Electrocardiol

  ;54():43-46. doi: S0022-0736(18)30918-X.
  
  Baroni Matteo, Colombo Giulia, Testoni Alessio, Arupi Michele, Lunati Maurizio, Cattafi Giuseppe
  
  
  
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• and Nocturnal Frontal Lobe Epilepsy: Identification and Characterization of a Novel Loss of Function Mutation.
  Front Mol Neurosci

  2019 ;12():17. doi: 10.3389/fnmol.2019.00017.
  
  Villa Chiara, Colombo Giulia, Meneghini Simone, Gotti Cecilia, Moretti Milena, Ferini-Strambi Luigi, Chisci Elisa, Giovannoni Roberto, Becchetti Andrea, Combi Romina
  
  Abstract
  
  Mutations in genes coding for subunits of the neuronal nicotinic acetylcholine receptor (nAChR) have been involved in familial sleep-related hypermotor epilepsy (also named autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE). Most of these mutations reside in and genes, coding for the ?4 and ?2 nAChR subunits, respectively. Two mutations with contrasting functional effects were also identified in the gene coding for the ?2 subunit. Here, we report the third mutation in the , found in a patient showing ADNFLE. The patient was examined by scalp EEG, contrast-enhanced brain magnetic resonance imaging (MRI), and nocturnal video-polysomnographic recording. All exons and the exon-intron boundaries of , , , , were amplified and Sanger sequenced. In the proband, we found a c.754T>C (p.Tyr252His) missense mutation located in the N-terminal ligand-binding domain and inherited from the mother. Functional studies were performed by transient co-expression of ?2 and ?2 , with either ?2 or ?4, in human embryonic kidney (HEK293) cells. Equimolar amounts of subunits expression were obtained by using F2A-based multi-cistronic constructs encoding for the genes relative to the nAChR subunits of interest and for the enhanced green fluorescent protein. The mutation reduced the maximal currents by approximately 80% in response to saturating concentrations of nicotine in homo- and heterozygous form, in both the ?2?4 and ?2?2 nAChR subtypes. The effect was accompanied by a strong right-shift of the concentration-response to nicotine. Similar effects were observed using ACh. Negligible effects were produced by ?2 on the current reversal potential. Moreover, binding of (±)-[H]Epibatidine revealed an approximately 10-fold decrease of both K and B (bound ligand in saturating conditions), in cells expressing ?2. The reduced B and whole-cell currents were not caused by a decrease in mutant receptor expression, as minor effects were produced by ?2 on the level of transcripts and the membrane expression of ?2?4 nAChR. Overall, these results suggest that ?2 strongly reduced the number of channels bound to the agonist, without significantly altering the overall channel expression. We conclude that mutations in are more commonly linked to ADNFLE than previously thought, and may cause a loss-of-function phenotype.
  
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• Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas.
  BMC Biol

  2019 01;17(1):3. doi: 10.1186/s12915-018-0622-4.
  
  Grugni Viola, Raveane Alessandro, Ongaro Linda, Battaglia Vincenza, Trombetta Beniamino, Colombo Giulia, Capodiferro Marco Rosario, Olivieri Anna, Achilli Alessandro, Perego Ugo A, Motta Jorge, Tribaldos Maribel, Woodward Scott R, Ferretti Luca, Cruciani Fulvio, Torroni Antonio, Semino Ornella
  
  Abstract
  
  BACKGROUND:
  Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America.
  
  RESULTS:
  Our analyses of 1.5?Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe.
  
  CONCLUSIONS:
  We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples.
  
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• Use of oral anticoagulant drugs in older patients with atrial fibrillation in internal medicine wards.
  Eur J Intern Med

  2018 06;52():e12-e14. doi: S0953-6205(18)30143-2.
  
  Proietti Marco, Antoniazzi Stefania, Monzani Valter, Santalucia Paola, Franchi Carlotta, , Fenoglio Luigi M, Melchio Remo, Fabris Fabrizio, Sartori Maria Teresa, Manfredini Roberto, De Giorgi Alfredo, Fabbian Fabio, Biolo Gianni, Zanetti Michela, Altamura Nicola, Sabbà Carlo, Suppressa Patrizia, Bandiera Francesco, Usai Carlo, Murialdo Giovanni, Fezza Francesca, Marra Alessio, Castelli Francesca, Cattaneo Federico, Beccati Valentina, di Minno Giovanni, Tufano Antonella, Contaldi Paola, Lupattelli Graziana, Bianconi Vanessa, Cappellini Domenica, Hu Cinzia, Minonzio Francesca, Fargion Silvia, Burdick Larry, Francione Paolo, Peyvandi Flora, Rossio Raffaella, Colombo Giulia, Monzani Valter, Ceriani Giuliana, Lucchi Tiziano, Brignolo Barbara, Manfellotto Dario, Caridi Irene, Corazza Gino Roberto, Miceli Emanuela, Padula Donatella, Fraternale Giacomo, Guasti Luigina, Squizzato Alessandro, Maresca Andrea, Liberato Nicola Lucio, Tognin Tiziana, Rozzini Renzo, Bellucci Francesco Baffa, Muscaritoli Maurizio, Molfino Alessio, Petrillo Enrico, Dore Maurizio, Mete Francesca, Gino Miriam, Franceschi Francesco, Gabrielli Maurizio, Perticone Francesco, Perticone Maria, Bertolotti Marco, Mussi Chiara, Borghi Claudio, Strocchi Enrico, Durazzo Marilena, Fornengo Paolo, Dallegri Franco, Ottonello Luciano Carlo, Salam Kassem, Caserza Lara, Barbagallo Mario, Di Bella Giovanna, Annoni Giorgio, Bruni Adriana Antonella, Odetti Patrizio, Nencioni Alessio, Monacelli Fiammetta, Napolitano Armando, Brucato Antonio, Valenti Anna, Castellino Pietro, Zanoli Luca, Mazzeo Marco
  
  
  
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• Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up.
  Blood Press

  2018 02;27(1):32-40. doi: 10.1080/08037051.2017.1378069.
  
  Meani Paolo, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Giupponi Luca, Stucchi Miriam, Varrenti Marisa, Vallerio Paola, Facchetti Rita, Grassi Guido, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects.
  
  MATERIALS AND METHODS:
  We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75?±?0.53 years.
  
  RESULTS:
  At baseline the mean age was 54.5?±?12.6 years, SBP and DBP were 141.3?±?18.6 and 86.4?±?10.4?mmHg and PWV was 8.56?±?1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (?PWV 0.87?±?3.05 m/s). PWV and ?PWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ?PWV showed a greater increase as compared to patients with controlled BP (1.46?±?3.67 vs 0.62?±?2.61 m/s, p?.05). The independent predictors of ?PWV were age, baseline PWV, baseline SBP/MBP and ?SBP/MBP.
  
  CONCLUSIONS:
  the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.
  
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• K. pneumoniae liver abscess following deferoxamine subcutaneous self-injection.
  Am J Hematol

  2017 May;92(5):480-481. doi: 10.1002/ajh.24675.
  
  Furlan Ludovico, Graziadei Giovanna, Colombo Giulia, Forzenigo Laura Virginia, Solbiati Monica
  
  
  
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• Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
  High Blood Press Cardiovasc Prev

  2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
  
  Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
  
  AIM:
  We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
  
  METHODS:
  30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
  
  RESULTS:
  On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
  
  CONCLUSIONS:
  In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
  
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• Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease.
  Open Heart

  ;3(2):e000472.
  
  Morici Nuccia, Farioli Laura, Losappio Laura Michelina, Colombo Giulia, Nichelatti Michele, Preziosi Donatella, Micarelli Gianluigi, Oliva Fabrizio, Giannattasio Cristina, Klugmann Silvio, Pastorello Elide Anna
  
  Abstract
  
  OBJECTIVE:
  To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).
  
  METHODS:
  We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2?years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.
  
  RESULTS:
  Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p
  CONCLUSIONS:
  In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2?years, demonstrating a possible long-term prognostic role of this biomarker.
  
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• Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation.
  Heart Vessels

  2016 May;31(5):722-33. doi: 10.1007/s00380-015-0654-4.
  
  Ammirati Enrico, Oliva Fabrizio G, Colombo Tiziano, Russo Claudio F, Cipriani Manlio G, Garascia Andrea, Guida Valentina, Colombo Giulia, Verde Alessandro, Perna Enrico, Cannata Aldo, Paino Roberto, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.
  
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• Ultrasonography versus computed tomography for suspected nephrolithiasis.
  Intern Emerg Med

  2015 Jun;10(4):515-6. doi: 10.1007/s11739-015-1192-x.
  
  Colombo Giulia, Solbiati Monica,
  
  
  
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• Age-adjusted D-dimer cutoff levels and pulmonary embolism.
  JAMA

  2014 Aug;312(5):557. doi: 10.1001/jama.2014.7604.
  
  Colombo Giorgio, Furlan Ludovico, Colombo Giulia
  
  
  
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• Blood pressure control in Italian essential hypertensives treated by general practitioners.
  Am J Hypertens

  2012 Nov;25(11):1182-7. doi: 10.1038/ajh.2012.108.
  
  Giannattasio Cristina, Cairo Matteo, Cesana Francesca, Alloni Marta, Sormani Paola, Colombo Giulia, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Adequate control of blood pressure (BP) is limited worldwide. This has serious consequences for public health because in hypertensive patients, uncontrolled BP is associated with a higher incidence of cardiovascular events, particularly stroke. The aim of this study was to investigate BP control in a cohort of treated patients with diagnosed hypertension, who were under general practitioner care in Italy.
  
  METHODS:
  Data were collected by 2,643 physicians on 8,572 individual Italian patients. Office BP was measured 5 min after seating each patient and then 3-5 min later. For each patient, data such as medical history of patients, physical examination data, antihypertensive drug usage, and self-BP measurement frequency were obtained.
  
  RESULTS:
  Male prevalence was 48.4%, and mean age was 64.3 ± 10.5 years. Based on the second measurement, BP control (
  CONCLUSIONS:
  In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.
  
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• Simvastatin reduces MMP1 expression in human smooth muscle cells cultured on polymerized collagen by inhibiting Rac1 activation.
  Arterioscler Thromb Vasc Biol

  2007 May;27(5):1043-9.
  
  Ferri Nicola, Colombo Giulia, Ferrandi Corrado, Raines Elaine W, Levkau Bodo, Corsini Alberto
  
  Abstract
  
  OBJECTIVE:
  Activation of collagen receptors expressed by smooth muscle cells induces matrix metalloproteinase (MMP) expression. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to interfere with integrin signaling, but their effects on collagen receptor-mediated MMP expression have not been investigated.
  
  METHODS AND RESULTS:
  In the present study, we show that simvastatin (3 micromol/L) reduces MMP1 expression and secretion in human smooth muscle cells cultured on polymerized type I collagen by 39.9+/-11.2% and 36.0+/-2.3%, respectively. Reduced MMP1 protein levels correlate with a similar decrease in MMP1 promoter activity (-33.0+/-8.9%), MMP1 mRNA levels (-37.8+/-10.5%), and attenuation of smooth muscle cell collagen degradation (-34.2+/-6.1%). Mevalonate, and the isoprenoid derivative geranylgeraniol, precursors of geranylgeranylated proteins, completely prevent the inhibitory effect of simvastatin on MMP1. Moreover, the protein geranylgeranyltransferase inhibitor GGTI-286 significantly decreases MMP1 expression. Retroviral overexpression of dominant-negative mutants of geranylgeranylated Rac1 lead to a reduction of MMP1 protein (-50.4+/-5.4%) and mRNA levels (-97.9+/-1.0%), and knockdown of Rac1 by small interfering RNA downregulates MMP1 expression. Finally, simvastatin reduces GTP-bound Rac1 expression levels in smooth muscle cells cultured on polymerized collagen.
  
  CONCLUSIONS:
  These results demonstrate that simvastatin, by inhibiting Rac1 activity, reduces MMP1 expression and collagen degradation in human smooth muscle cells.
  
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• FSH and LH together in ovarian stimulation.
  Eur J Obstet Gynecol Reprod Biol

  2004 Jul;115 Suppl 1():S34-9.
  
  Levi-Setti Paolo E, Cavagna Mario, Baggiani Annamaria, Zannoni Elena, Colombo Giulia V, Liprandi Valeria
  
  Abstract
  
  The authors review the physiology of the ovulatory cycle and the role of the gonadotrophins in ovulation induction in patients with anovulatory disorders and in multifollicular development for assisted reproductive technologies. The use of gonadotrophins with luteinizing hormone (LH) activity and the use of recombinant LH associated with follicle stimulating hormone (FSH) are discussed. The authors point out that administration of gonadotrophins with LH activity is essential in hypogonadotropic hypogonadal anovulation, and data available in the medical literature allow the conclusion that recombinant LH may be added to all ovarian stimulation protocols because it is difficult to determine which patients will benefit from LH administration and there is no evidence that LH affects adversely the outcome of ovarian stimulation. The use of recombinant LH in addition to recombinant FSH may be particularly useful when a GnRH antagonist is associated with the ovarian stimulation regimen, by preventing the fall in estradiol and diminishing FSH requirements.
  
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