373 results on '"Sali, M."'
Search Results
2. ScRNAbox: empowering single-cell RNA sequencing on high performance computing systems
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Thomas, Rhalena A., Fiorini, Michael R., Amiri, Saeid, Fon, Edward A., and Farhan, Sali M. K.
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- 2024
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3. Secrets and lies of host–microbial interactions: MHC restriction and trans-regulation of T cell trafficking conceal the role of microbial agents on the edge between health and multifactorial/complex diseases
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Ria, F., Delogu, G., Ingrosso, L., Sali, M., and Di Sante, G.
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- 2024
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4. Tri-Rotor Propeller Design Concept, Optimization and Analysis of the Lift Efficiency During Hovering
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Piancastelli, L. and Sali, M.
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- 2023
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5. Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function
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Steering Committee, Landi, Francesco, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field investigators, Gastroenterology team, Porcari, Serena, Settanni, Carlo Romano, Geriatric team, Benvenuto, Francesca, Bramato, Giulia, Brandi, Vincenzo, Carfì, Angelo, Ciciarello, Francesca, Fabrizi, Sofia, Galluzzo, Vincenzo, Lo Monaco, Maria Rita, Martone, Anna Maria, Marzetti, Emanuele, Napolitano, Carmen, Pagano, Francesco Cosimo, Pais, Cristina, Rocchi, Sara, Rota, Elisabetta, Salerno, Andrea, Tosato, Matteo, Tritto, Marcello, Zazzara, Maria Beatrice, Calvani, Riccardo, Catalano, Lucio, Picca, Anna, Savera, Giulia, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, Giovanni, Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, Federica, Cacciatore, Stefano, Infectious disease team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, A., Di Gianbenedetto, Simona, Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine team, Stella, Leonardo, Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Gertrude, Zocco, M.A., Microbiology team, Sanguinetti, Maurizio, Cattani, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, G., Cozzupoli, G.M., Culiersi, C., Otolaryngology team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Y., Tricarico, L., Santantonio, M., Pediatric team, Buonsenso, Danilo, Valentini, P., Pata, D., Sinatti, D., De Rose, C., Pneumology team, Richeldi, Luca, Lombardi, Francesco, Calabrese, A., Leone, Paolo Maria, Calvello, Maria Rosaria, Intini, Enrica, Montemurro, Giuliano, Psychiatric team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., odica, M., Radiology team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology team, Paglionico, Annamaria, Petricca, Luca, Gigante, Luca, Natalello, G., Fedele, A.L., Lizzio, M.M., Tolusso, B., Di Mario, Clara, Alivernini, S., Vascular team, Santoliquido, Angelo, Santoro, Luca, Di Giorgio, Angela, Nesci, Antonio, and Popolla, V.
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- 2022
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6. Action video games normalise the phonemic awareness in pre-readers at risk for developmental dyslexia
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Bertoni, S, Andreola, C, Mascheretti, S, Franceschini, S, Ruffino, M, Trezzi, V, Molteni, M, Sali, M, Salandi, A, Gaggi, O, Palazzi, C, Gori, S, Facoetti, A, Bertoni S., Andreola C., Mascheretti S., Franceschini S., Ruffino M., Trezzi V., Molteni M., Sali M. E., Salandi A., Gaggi O., Palazzi C., Gori S., Facoetti A., Bertoni, S, Andreola, C, Mascheretti, S, Franceschini, S, Ruffino, M, Trezzi, V, Molteni, M, Sali, M, Salandi, A, Gaggi, O, Palazzi, C, Gori, S, Facoetti, A, Bertoni S., Andreola C., Mascheretti S., Franceschini S., Ruffino M., Trezzi V., Molteni M., Sali M. E., Salandi A., Gaggi O., Palazzi C., Gori S., and Facoetti A.
- Abstract
Action video-games (AVGs) could improve reading efficiency, enhancing not only visual attention but also phonological processing. Here we tested the AVG effects upon three consolidated language-based predictors of reading development in a sample of 79 pre-readers at-risk and 41 non-at-risk for developmental dyslexia. At-risk children were impaired in either phonemic awareness (i.e., phoneme discrimination task), phonological working memory (i.e., pseudoword repetition task) or rapid automatized naming (i.e., RAN of colours task). At-risk children were assigned to different groups by using an unequal allocation randomization: (1) AVG (n = 43), (2) Serious Non-Action Video Game (n = 11), (3) treatment-as-usual (i.e., speech therapy, n = 11), and (4) waiting list (n = 14). Pre- and post-training comparisons show that only phonemic awareness has a significantly higher improvement in the AVG group compared to the waiting list, the non-AVG, and the treatment-as-usual groups, as well as the combined active groups (n = 22). This cross-modal plastic change: (i) leads to a recovery in phonemic awareness when compared to the not-at-risk pre-readers; (ii) is present in more than 80% of AVG at-risk pre-readers, and; (iii) is maintained at a 6-months follow-up. The present findings indicate that this specific multisensory attentional training positively affects how phonemic awareness develops in pre-readers at risk for developmental dyslexia, paving the way for innovative prevention programs.
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- 2024
7. Enhancing variant of uncertain significance (VUS) interpretation in neurogenetics: collaborative experiences from a tertiary care centre.
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Horowitz, Kayla, Fotopoulos, Nellie H., Mistry, Alana J., Simo, Justin, Medeiros, Miranda, Bucco, Isabela D., Ginsberg, Mia, Dwosh, Emily, La Piana, Roberta, Rouleau, Guy A., Dilliott, Allison A., and Farhan, Sali M. K.
- Abstract
Background The findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes of multidisciplinary VUS Rounds, implemented at a neurological disease tertiary care centre, which aid in interpreting and communicating VUS identified in our neurogenetics patient population. Methods VUS Rounds brought together genetic counsellors, molecular geneticists and scientists to evaluate VUS against genomic and phenotypic evidence and assign an internal temperature classification of 'VUS Hot', 'True VUS' or 'VUS Cold', corresponding to potential pathogenicity. Biweekly meetings were held among the committee to deliberate variant classifications, determine additional clinical management actions and discuss nuances of VUS result communication. Results In total, 143 VUS identified in 72 individuals with neurological disease were curated between October 2022 and December 2023. Of these, 12.6% were classified as VUS Hot, carried by 22.2% of the individuals, allowing for prioritisation of additional evaluation to determine potential pathogenicity of the variants, such as clinical follow-up or segregation analysis. In contrast, 45.4% of VUS were Cold and could be eliminated from further consideration in the carrier's care. We thoroughly evaluated the various evidence that contributed to our VUS classifications and resulting clinical actions. Conclusions The assessment of VUS leveraging multidisciplinary collaboration allowed us to delineate required follow-up analyses for our neurology patient population. Integration of VUS Rounds into healthcare practices ensures equitable knowledge dissemination among HCPs and effective incorporation of uncertain genetic results into patient care. [ABSTRACT FROM AUTHOR]
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- 2025
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8. Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3′UTR protect against ALS
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Eitan, Chen, Siany, Aviad, Barkan, Elad, Olender, Tsviya, van Eijk, Kristel R., Moisse, Matthieu, Farhan, Sali M. K., Danino, Yehuda M., Yanowski, Eran, Marmor-Kollet, Hagai, Rivkin, Natalia, Yacovzada, Nancy Sarah, Hung, Shu-Ting, Cooper-Knock, Johnathan, Yu, Chien-Hsiung, Louis, Cynthia, Masters, Seth L., Kenna, Kevin P., van der Spek, Rick A. A., Sproviero, William, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Jones, Ashley R., Elbaz-Alon, Yael, Cohen, Yahel, Chapnik, Elik, Rothschild, Daphna, Weissbrod, Omer, Beck, Gilad, Ainbinder, Elena, Ben-Dor, Shifra, Werneburg, Sebastian, Schafer, Dorothy P., Brown, Jr, Robert H., Shaw, Pamela J., Van Damme, Philip, van den Berg, Leonard H., Phatnani, Hemali, Segal, Eran, Ichida, Justin K., Al-Chalabi, Ammar, Veldink, Jan H., and Hornstein, Eran
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- 2022
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9. Targeting Tau Mitigates Mitochondrial Fragmentation and Oxidative Stress in Amyotrophic Lateral Sclerosis
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Petrozziello, Tiziana, Bordt, Evan A., Mills, Alexandra N., Kim, Spencer E., Sapp, Ellen, Devlin, Benjamin A., Obeng-Marnu, Abigail A., Farhan, Sali M. K., Amaral, Ana C., Dujardin, Simon, Dooley, Patrick M., Henstridge, Christopher, Oakley, Derek H., Neueder, Andreas, Hyman, Bradley T., Spires-Jones, Tara L., Bilbo, Staci D., Vakili, Khashayar, Cudkowicz, Merit E., Berry, James D., DiFiglia, Marian, Silva, M. Catarina, Haggarty, Stephen J., and Sadri-Vakili, Ghazaleh
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- 2022
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10. MTSviewer: A database to visualize mitochondrial targeting sequences, cleavage sites, and mutations on protein structures
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Andrew N. Bayne, Jing Dong, Saeid Amiri, Sali M. K. Farhan, and Jean-François Trempe
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Medicine ,Science - Abstract
Mitochondrial dysfunction is implicated in a wide array of human diseases ranging from neurodegenerative disorders to cardiovascular defects. The coordinated localization and import of proteins into mitochondria are essential processes that ensure mitochondrial homeostasis. The localization and import of most mitochondrial proteins are driven by N-terminal mitochondrial targeting sequences (MTS’s), which interact with import machinery and are removed by the mitochondrial processing peptidase (MPP). The recent discovery of internal MTS’s—those which are distributed throughout a protein and act as import regulators or secondary MPP cleavage sites–has expanded the role of both MTS’s and MPP beyond conventional N-terminal regulatory pathways. Still, the global mutational landscape of MTS’s remains poorly characterized, both from genetic and structural perspectives. To this end, we have integrated a variety of tools into one harmonized R/Shiny database called MTSviewer (https://neurobioinfo.github.io/MTSvieweR/), which combines MTS predictions, cleavage sites, genetic variants, pathogenicity predictions, and N-terminomics data with structural visualization using AlphaFold models of human and yeast mitochondrial proteomes. Using MTSviewer, we profiled all MTS-containing proteins across human and yeast mitochondrial proteomes and provide multiple case studies to highlight the utility of this database.
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- 2023
11. Sex-stratified RNA-seq analysis reveals traumatic brain injury-induced transcriptional changes in the female hippocampus conducive to dementia
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Michael R. Fiorini, Allison A. Dilliott, and Sali M. K. Farhan
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traumatic brain injury ,dementia ,RNA sequencing ,transcriptome ,hippocampus ,sex ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
IntroductionTraumatic brain injury (TBI), resulting from a violent force that causes functional changes in the brain, is the foremost environmental risk factor for developing dementia. While previous studies have identified specific candidate genes that may instigate worse outcomes following TBI when mutated, TBI-induced changes in gene expression conducive to dementia are critically understudied. Additionally, biological sex seemingly influences TBI outcomes, but the discrepancies in post-TBI gene expression leading to progressive neurodegeneration between the sexes have yet to be investigated.MethodsWe conducted a whole-genome RNA sequencing analysis of post-mortem brain tissue from the parietal neocortex, temporal neocortex, frontal white matter, and hippocampus of 107 donors characterized by the Aging, Dementia, and Traumatic Brain Injury Project. Our analysis was sex-stratified and compared gene expression patterns between TBI donors and controls, a subset of which presented with dementia.ResultsWe report three candidate gene modules from the female hippocampus whose expression correlated with dementia in female TBI donors. Enrichment analyses revealed that the candidate modules were notably enriched in cardiac processes and the immune-inflammatory response, among other biological processes. In addition, multiple candidate module genes showed a significant positive correlation with hippocampal concentrations of monocyte chemoattractant protein-1 in females with post-TBI dementia, which has been previously described as a potential biomarker for TBI and susceptibility to post-injury dementia. We concurrently examined the expression profiles of these candidate modules in the hippocampus of males with TBI and found no apparent indicator that the identified candidate modules contribute to post-TBI dementia in males.DiscussionHerein, we present the first sex-stratified RNA sequencing analysis of TBI-induced changes within the transcriptome that may be conducive to dementia. This work contributes to our current understanding of the pathophysiological link between TBI and dementia and emphasizes the growing interest in sex as a biological variable affecting TBI outcomes.
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- 2022
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12. Contribution of rare variant associations to neurodegenerative disease presentation
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Allison A. Dilliott, Abdalla Abdelhady, Kelly M. Sunderland, Sali M. K. Farhan, Agessandro Abrahao, Malcolm A. Binns, Sandra E. Black, Michael Borrie, Leanne K. Casaubon, Dar Dowlatshahi, Elizabeth Finger, Corinne E. Fischer, Andrew Frank, Morris Freedman, David Grimes, Ayman Hassan, Mandar Jog, Sanjeev Kumar, Donna Kwan, Anthony E. Lang, Jennifer Mandzia, Mario Masellis, Adam D. McIntyre, Stephen H. Pasternak, Bruce G. Pollock, Tarek K. Rajji, Ekaterina Rogaeva, Demetrios J. Sahlas, Gustavo Saposnik, Christine Sato, Dallas Seitz, Christen Shoesmith, Thomas D. L. Steeves, Richard H. Swartz, Brian Tan, David F. Tang-Wai, Maria C. Tartaglia, John Turnbull, Lorne Zinman, ONDRI Investigators, and Robert A. Hegele
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Medicine ,Genetics ,QH426-470 - Abstract
Abstract Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson’s disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.
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- 2021
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13. Evidence of synergism among three genetic variants in a patient with LMNA-related lipodystrophy and amyotrophic lateral sclerosis leading to a remarkable nuclear phenotype
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Volkening, Kathryn, Farhan, Sali M. K., Kao, Jessica, Leystra-Lantz, Cheryl, Ang, Lee Cyn, McIntyre, Adam, Wang, Jian, Hegele, Robert A., and Strong, Michael J.
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- 2021
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14. Multiple antimicrobial and immune-modulating activities of cysteamine in infectious diseases
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Alonzi, T., Aiello, Antimo, Sali, Michela, Delogu, Giovanni, Villella, V. R., Raia, V., Nicastri, E., Piacentini, M., Goletti, Delia, Aiello A., Sali M. (ORCID:0000-0003-3609-2990), Delogu G. (ORCID:0000-0003-0182-8267), Goletti D., Alonzi, T., Aiello, Antimo, Sali, Michela, Delogu, Giovanni, Villella, V. R., Raia, V., Nicastri, E., Piacentini, M., Goletti, Delia, Aiello A., Sali M. (ORCID:0000-0003-3609-2990), Delogu G. (ORCID:0000-0003-0182-8267), and Goletti D.
- Abstract
Infectious diseases are a major threat to global health and cause millions of deaths every year, particularly in developing countries. The emergence of multidrug resistance challenges current antimicrobial treatments, inducing uncertainty in therapeutic protocols. New compounds are therefore necessary. A drug repurposing approach could play a critical role in developing new treatments used either alone or in combination with standard therapy regimens. Herein, we focused on cysteamine, an aminothiol endogenously synthesized by human cells during the degradation of coenzyme-A, which is a drug approved for the treatment of nephropathic cystinosis. Cysteamine influences many biological processes due to the presence of the highly reactive thiol group. This review provides an overview of cysteamine-mediated effects on different viruses, bacteria and parasites, with a particular focus on infections caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), and Pseudomonas aeruginosa. Evidences for a potential use of cysteamine as a direct antimicrobial agent and/or a host-directed therapy, either alone or in combination with other antimicrobial drugs, are described.
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- 2024
15. Secrets and lies of host-microbial interactions: MHC restriction and trans-regulation of T cell trafficking conceal the role of microbial agents on the edge between health and multifactorial/complex diseases
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Ria, Francesco, Delogu, Giovanni, Ingrosso, L, Sali, Michela, Di Sante, Gabriele, Ria, F (ORCID:0000-0002-8444-0307), Delogu, G (ORCID:0000-0003-0182-8267), Sali, M (ORCID:0000-0003-3609-2990), Di Sante, G (ORCID:0000-0001-6608-3388), Ria, Francesco, Delogu, Giovanni, Ingrosso, L, Sali, Michela, Di Sante, Gabriele, Ria, F (ORCID:0000-0002-8444-0307), Delogu, G (ORCID:0000-0003-0182-8267), Sali, M (ORCID:0000-0003-3609-2990), and Di Sante, G (ORCID:0000-0001-6608-3388)
- Abstract
Here we critically discuss data supporting the view that microbial agents (pathogens, pathobionts or commensals alike) play a relevant role in the pathogenesis of multifactorial diseases, but their role is concealed by the rules presiding over T cell antigen recognition and trafficking. These rules make it difficult to associate univocally infectious agents to diseases' pathogenesis using the paradigm developed for canonical infectious diseases. (Cross-)recognition of a variable repertoire of epitopes leads to the possibility that distinct infectious agents can determine the same disease(s). There can be the need for sequential infection/colonization by two or more microorganisms to develop a given disease. Altered spreading of infectious agents can determine an unwanted activation of T cells towards a pro-inflammatory and trafficking phenotype, due to differences in the local microenvironment. Finally, trans-regulation of T cell trafficking allows infectious agents unrelated to the specificity of T cell to modify their homing to target organs, thereby driving flares of disease. The relevant role of microbial agents in largely prevalent diseases provides a conceptual basis for the evaluation of more specific therapeutic approaches, targeted to prevent (vaccine) or cure (antibiotics and/or Biologic Response Modifiers) multifactorial diseases.
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- 2024
16. Autism spectrum disorder prevalence in Italy: a nationwide study promoted by the Ministry of Health
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Scattoni, M, Fatta, L, Micai, M, Sali, M, Bellomo, M, Salvitti, T, Fulceri, F, Castellano, A, Molteni, M, Gambino, G, Posada, M, Romano, G, Puopolo, M, Scattoni M. L., Fatta L. M., Micai M., Sali M. E., Bellomo M., Salvitti T., Fulceri F., Castellano A., Molteni M., Gambino G., Posada M., Romano G., Puopolo M., Scattoni, M, Fatta, L, Micai, M, Sali, M, Bellomo, M, Salvitti, T, Fulceri, F, Castellano, A, Molteni, M, Gambino, G, Posada, M, Romano, G, Puopolo, M, Scattoni M. L., Fatta L. M., Micai M., Sali M. E., Bellomo M., Salvitti T., Fulceri F., Castellano A., Molteni M., Gambino G., Posada M., Romano G., and Puopolo M.
- Abstract
Background: This nationwide study aimed to estimate Autism Spectrum Disorder (ASD) prevalence in 7–9-year-old Italian children. Promoted by Italy's Ministry of Health and coordinated by the National Observatory for Autism at the National Institute of Health, it covered schools in northern (Lecco and Monza-Brianza), central (Rome and its province), and southern (Palermo and its province) regions from February 24, 2016, to February 23, 2018, using a multi-stage approach defined by the European Union's ASD network. Methods: Phase one identified ASD-diagnosed children in mainstream schools through local Ministry of Education (MoE) disability registries. Phase two had a subset of schools screen 7–9-year-olds using the Social Communication Questionnaire-Life version (SCQ-L). Those with SCQ-L scores of 15 + underwent clinical consultation for ASD symptoms, cognitive abilities, and life skills. To counter potential false negatives, 20% scoring 11–14 were randomly assessed via Autism Diagnostic Interview-Revised (ADI-R). Results: MoE data revealed 9.8 per 1000 certified ASD children in the north, 12.2 in the central, and 10.3 in the south. In phase two, 35,823 SCQ-L questionnaires were distributed across 198 schools (northern: 11,190 in 49 schools, central: 13,628 in 87 schools, southern: 11,005 in 62 schools). Of SCQ-L respondents, 2.4% (n = 390) scored above the 15 cutoff. Among these, 100 had ASD diagnoses, and 50 had other diagnoses. Among 115 families assessed, 16.5% (n = 19) received ASD diagnoses. Conclusions: The estimated prevalence of ASD in Italy was 13.4 (11.3–16.0) per 1,000 children aged 7–9 years, with a male-to-female ratio of 4.4:1. It will guide national policies in enhancing services tailored to the specific needs of autistic children.
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- 2023
17. Myasthenia Gravis and Pregnancy: A Case Report
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Jamaleddine, A., primary, Sali, M., additional, Trabelsi, M., additional, Asmouki, H., additional, Aboulfallah, A., additional, Fakhir, B., additional, Bassir, A., additional, Harou, K., additional, Boukhani, L., additional, and Soummani, A., additional
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- 2024
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18. Regulatory interactions between daptomycin‐ and bacitracin‐responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis.
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Morris, Sali M., Wiens, Laura, Rose, Olivia, Fritz, Georg, Rogers, Tim, and Gebhard, Susanne
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ENTEROCOCCUS faecalis , *DRUG resistance in bacteria , *ENTEROCOCCUS , *ENTEROCOCCAL infections , *ATP-binding cassette transporters , *BACITRACIN - Abstract
Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope‐acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two‐component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP‐resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS‐target genes under dual control, where expression is directly controlled by SapRS, which itself is up‐regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion
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Rossella Spataro, Maria Kousi, Sali M. K. Farhan, Jason R. Willer, Jay P. Ross, Patrick A. Dion, Guy A. Rouleau, Mark J. Daly, Benjamin M. Neale, Vincenzo La Bella, and Nicholas Katsanis
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Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases. Results We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Starting with the index case, a consanguineous family of Italian origin, we performed whole-exome sequencing and identified candidate pathogenic mutations in 35 genes, 27 of which were homozygous. We next parsed all candidates against a cohort of 3641 ALS cases; only ATP13A2 was found to harbor recessive changes, in a patient with juvenile-onset ALS, similar to the index case. In vivo complementation of ATP13A2 using a zebrafish surrogate model that focused on the assessment of motor neuron morphology and cerebellar integrity confirmed the role of this gene in central and peripheral nervous system maintenance and corroborated the damaging direction of effect of the change detected in the index case of this study. Conclusions We here expand the phenotypic spectrum associated with genetic variants in ATP13A2 that previously comprised Kufor-Rakeb syndrome, spastic paraplegia 78, and neuronal ceroid lipofuscinosis type 12 (CLN12), to also include juvenile-onset ALS, as supported by both genetic and functional data. Our findings highlight the importance of establishing a complete genetic profile towards obtaining an accurate clinical diagnosis.
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- 2019
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20. Evaluating the Utility of REVEL and CADD for Interpreting Variants in Amyotrophic Lateral Sclerosis Genes
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Fiorini, Michael R., primary, Dilliott, Allison A., additional, and Farhan, Sali M. K., additional
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- 2023
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21. Identification of gene fusions associated with amyotrophic lateral sclerosis.
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Raghav, Yogindra, Dilliott, Allison A., Petrozziello, Tiziana, Kim, Spencer E., Berry, James D., Cudkowicz, Merit E., Vakili, Khashayar, Fraenkel, Ernest, Farhan, Sali M. K., and Sadri‐Vakili, Ghazaleh
- Abstract
Introduction/Aims: Genetics is an important risk factor for amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Recent findings demonstrate that in addition to specific genetic mutations, structural variants caused by genetic instability can also play a causative role in ALS. Genomic instability can lead to deletions, duplications, insertions, inversions, and translocations in the genome, and these changes can sometimes lead to fusion of distinct genes into a single transcript. Gene fusion events have been studied extensively in cancer; however, they have not been thoroughly investigated in ALS. The aim of this study was to determine whether gene fusions are present in ALS. Methods: Gene fusions were identified using STAR Fusion v1.10.0 software in bulk RNA‐Seq data from human postmortem samples from publicly available data sets from Target ALS and the New York Genome Center ALS Consortium. Results: We report the presence of gene fusion events in several brain regions as well as in spinal cord samples in ALS. Although most gene fusions were intra‐chromosomal events between neighboring genes and present in both ALS and control samples, there was a significantly greater number of unique gene fusions in ALS compared to controls. Lastly, we identified specific gene fusions with a significant burden in ALS, that were absent from both control samples and known cancer gene fusion databases. Discussion: Collectively, our findings reveal an enrichment of gene fusions in ALS and suggest that these events may be an additional genetic cause linked to ALS pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2024
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22. KCTD7‐related progressive myoclonic epilepsy: Report of 42 cases and review of literature.
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Yoganathan, Sangeetha, Whitney, Robyn, Thomas, Maya, Danda, Sumita, Chettali, Akbar Mohamed, Prasad, Asuri N., Farhan, Sali M. K., AlSowat, Daad, Abukhaled, Musaad, Aldhalaan, Hesham, Gowda, Vykuntaraju K., Kinhal, Uddhava V., Bylappa, Arun Y., Konanki, Ramesh, Lingappa, Lokesh, Parchuri, Bindu Madhavi, Appendino, Juan P., Scantlebury, Morris H., Cunningham, Jessie, and Hadjinicolaou, Aristides
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EPILEPSY ,OPSOCLONUS-Myoclonus syndrome ,NEURONAL ceroid-lipofuscinosis ,NATURAL history ,MYOCLONUS - Abstract
Objective: KCTD7‐related progressive myoclonic epilepsy (PME) is a rare autosomal‐recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort. Methods: Families with molecularly confirmed diagnoses of KCTD7‐related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging‐related variables were collected and summarized. Results: Forty‐two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75–22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty‐one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5–21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7‐related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3–18 years). Significance: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7‐related disorders. Early onset drug‐resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials. [ABSTRACT FROM AUTHOR]
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- 2024
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23. The two‐component system CroRS acts as a master regulator of cell envelope homeostasis to confer antimicrobial tolerance in the bacterial pathogen Enterococcus faecalis
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Todd Rose, Francesca O., primary, Darnell, Rachel L., additional, Morris, Sali M., additional, Rose, Olivia E., additional, Paxie, Olivia, additional, Campbell, Georgia, additional, Cook, Gregory M., additional, and Gebhard, Susanne, additional
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- 2023
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24. Characterizing proteomic and transcriptomic features of missense variants in amyotrophic lateral sclerosis genes
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Dilliott, Allison A, primary, Kwon, Seulki, additional, Rouleau, Guy A, additional, Iqbal, Sumaiya, additional, and Farhan, Sali M K, additional
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- 2023
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25. Rare neurovascular genetic and imaging markers across neurodegenerative diseases
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Dilliott, Allison A, Berberian, Stephanie A, Sunderland, Kelly M, Binns, Malcolm A, Zimmer, Julia, Ozzoude, Miracle, Scott, Christopher J M, Gao, Fuqiang, Lang, Anthony E, Breen, David P, Tartaglia, Maria C, Tan, Brian, Swartz, Richard H, Rogaeva, Ekaterina, Borrie, Michael, Finger, Elizabeth, Fischer, Corinne E, Frank, Andrew, Freedman, Morris, Kumar, Sanjeev, Pasternak, Stephen, Pollock, Bruce G, Rajji, Tarek K, Tang-Wai, David F, Abrahao, Agessandro, Turnbull, John, Zinman, Lorne, Casaubon, Leanne, Dowlatshahi, Dar, Hassan, Ayman, Mandzia, Jennifer, Sahlas, Demetrios, Saposnik, Gustavo, Grimes, David, Marras, Connie, Steeves, Thomas, Masellis, Mario, Farhan, Sali M K, Bartha, Robert, Symons, Sean, Hegele, Robert A, Black, Sandra E, and Ramirez, Joel
- Abstract
INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status.METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1).RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood.DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.
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- 2023
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26. Clinical testing panels for ALS : global distribution, consistency, and challenges
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Dilliott, Allison A., Al Nasser, Ahmad, Elnagheeb, Marwa, Fifita, Jennifer, Henden, Lyndal, Keseler, Ingrid M., Lenz, Steven, Marriott, Heather, Mccann, Emily, Mesaros, Maysen, Opie-Martin, Sarah, Owens, Emma, Palus, Brooke, Ross, Justyne, Wang, Zhanjun, White, Hannah, Al-Chalabi, Ammar, Andersen, Peter M., Benatar, Michael, Blair, Ian, Cooper-Knock, Johnathan, Harrington, Elizabeth A., Heckmann, Jeannine, Landers, John, Moreno, Cristiane, Nel, Melissa, Rampersaud, Evadnie, Roggenbuck, Jennifer, Rouleau, Guy, Traynor, Bryan, Van Blitterswijk, Marka, Van Rheenen, Wouter, Veldink, Jan, Weishaupt, Jochen, Drury, Luke, Harms, Matthew B., Farhan, Sali M. K., Dilliott, Allison A., Al Nasser, Ahmad, Elnagheeb, Marwa, Fifita, Jennifer, Henden, Lyndal, Keseler, Ingrid M., Lenz, Steven, Marriott, Heather, Mccann, Emily, Mesaros, Maysen, Opie-Martin, Sarah, Owens, Emma, Palus, Brooke, Ross, Justyne, Wang, Zhanjun, White, Hannah, Al-Chalabi, Ammar, Andersen, Peter M., Benatar, Michael, Blair, Ian, Cooper-Knock, Johnathan, Harrington, Elizabeth A., Heckmann, Jeannine, Landers, John, Moreno, Cristiane, Nel, Melissa, Rampersaud, Evadnie, Roggenbuck, Jennifer, Rouleau, Guy, Traynor, Bryan, Van Blitterswijk, Marka, Van Rheenen, Wouter, Veldink, Jan, Weishaupt, Jochen, Drury, Luke, Harms, Matthew B., and Farhan, Sali M. K.
- Abstract
Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.
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- 2023
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27. Graphene–Curcumin Coatings Resistant to SARS-CoV-2 and Mycobacteria for the Production of Personal Protective Equipment
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De Maio, Flavio, Santarelli, Giulia, Palmieri, V., Perini, Giordano, Salustri, Alessandro, Palucci, Ivana, Delli Carpini, Giovanni, Augello, A., Sanguinetti, Maurizio, De Spirito, Marco, Sali, Michela, Delogu, Giovanni, Papi, Massimiliano, De Maio F., Santarelli G., Perini G. (ORCID:0000-0001-9452-8479), Salustri A., Palucci I., Delli Carpini G., Sanguinetti M. (ORCID:0000-0002-9780-7059), De Spirito M. (ORCID:0000-0003-4260-5107), Sali M. (ORCID:0000-0003-3609-2990), Delogu G. (ORCID:0000-0003-0182-8267), Papi M. (ORCID:0000-0002-0029-1309), De Maio, Flavio, Santarelli, Giulia, Palmieri, V., Perini, Giordano, Salustri, Alessandro, Palucci, Ivana, Delli Carpini, Giovanni, Augello, A., Sanguinetti, Maurizio, De Spirito, Marco, Sali, Michela, Delogu, Giovanni, Papi, Massimiliano, De Maio F., Santarelli G., Perini G. (ORCID:0000-0001-9452-8479), Salustri A., Palucci I., Delli Carpini G., Sanguinetti M. (ORCID:0000-0002-9780-7059), De Spirito M. (ORCID:0000-0003-4260-5107), Sali M. (ORCID:0000-0003-3609-2990), Delogu G. (ORCID:0000-0003-0182-8267), and Papi M. (ORCID:0000-0002-0029-1309)
- Abstract
Respiratory tract infections represent the main cause of death from infectious diseases worldwide. SARS-CoV-2 infection (i.e. COVID-19) added to the existing global burden of respiratory tract infections, including tuberculosis. Among nanomaterials for fabric functionalization, graphene, in combination with hydrophobic molecules such as phytochemicals, represents a promising low-cost alternative to antibiotics. In this work, we used graphene and curcumin to create fabric coatings on cotton and polyester for the production of personal protective equipment resistant to infective agents. These coatings ensure the trapping of microorganisms via interaction with SARS-CoV-2 or mycobacteria surface and inhibit microbial infections.
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- 2023
28. IL CARICO SOCIO-SANITARIO DELLA DEPRESSIONE MAGGIORE NEGLI ADULTI
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ANTONAZZO, IPPAZIO COSIMO, Sali, M, MAZZAGLIA, GIAMPIERO, SALI, MARIA ENRICA, ANTONAZZO, IPPAZIO COSIMO, Sali, M, MAZZAGLIA, GIAMPIERO, and SALI, MARIA ENRICA
- Abstract
Introduzione: il Disturbo Depressivo Maggiore è la seconda causa che determina anni vissuti con disabilità nel mondo, con un elevato carico economico e sociale. Il presente studio si propone di valutare in dettaglio il burden socio-economico complessivo della della Depressione maggiore in età adulta in Italia. Metodi: è stato condotto uno studio osservazionale, multicentrico e longitudinale sul costo della malattia su pazienti di età compresa tra 18 e 65 anni con diagnosi di Depressione maggiore che iniziavano o apportavano modifiche alla propria terapia antidepressiva. I sintomi depressivi sono stati valutati con scale cliniche specifiche ed è stata rilevata anche la qualità della vita correlata alla salute. Sono stati raccolti i dati relativi al consumo di risorse sanitarie e la perdita di produttività per stimare i costi della Depressione maggiore. Risultati: La gravità della Depressione maggiore era maggiore durante le visite di arruolamento e diminuiva durante il periodo di osservazione, come riportato da tutte le scale cliniche. È stato anche osservato un miglioramento significativo dei punteggi sulla qualità di vita. Le spese mediche dirette aumentavano nei primi 3 mesi e diminuivano nel tempo (0-3° mese: € 155,9 per paziente-mese, 3°-6° mese: € 144,7 e 6°-12° mese: € 108,9). Anche i costi indiretti hanno mostrato un andamento simile con € 386,3 per paziente-mese per i primi 3 mesi dopo l'arruolamento e € 179,9 negli ultimi 6 mesi di osservazione. Limitazioni: la dimensione del campione era piccola e nello studio non era presente alcun gruppo di controllo; non da escludere la possibilità della presenza di bias di selezione. Conclusione: i risultati suggeriscono che la Depressione maggiore è un problema di salute mentale associato a un maggiore carico socio-economico che varia al variare della gravità dei sintomi. Questi risultati forniscono informazioni sulla complessità e sul burden della Depressione maggiore, e permettono di porre attenzione, Background: Major Depressive Disorder (MDD) is the second main cause of years lived with disabilities in the world, with high economic and social burden. This study aims to assess in detail the overall socio-economic burden of adult MDD in Italy. Methods: An observational, multicenter, longitudinal cost of illness study was conducted on patients aged 18-65 years with a diagnosis of MDD starting antidepressant therapy. Depressive symptoms were assessed with specific clinical scales and Health Related Quality of Life (HRQoL) was also detected. The healthcare resources consumption and productivity loss were also collected to estimate the costs of MDD. Results: The MDD severity was higher during the enrolment visits and decrease during the observational period, as reported by all clinical scales. A significant improvement in HRQoL scores was also observed. Direct medical costs were higher in the first 3 months and decrease over time (0-3rd months: € 155.9 per patient-month, 3 rd -6 th months: € 144.7, and 6 th -12 th months: € 108.9). Indirect costs also showed a similar trend with € 386.3 per patient-month for the first 3 months after enrollment and € 179.9 in the last 6 months of observation. Limitations: The sample size was small and no control group was present in the study; furthermore there may be a selection bias. Conclusion: Results suggest that MDD is a mental health problem associated with higher socio- economic burden that varies with severity of symptoms. These results provide information on complexity and burden of MDD, emphasizing the importance of including Depressive disorders as a public-health priority.
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- 2023
29. MTSviewer: A database to visualize mitochondrial targeting sequences, cleavage sites, and mutations on protein structures
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Bayne, Andrew N., primary, Dong, Jing, additional, Amiri, Saeid, additional, Farhan, Sali M. K., additional, and Trempe, Jean-François, additional
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- 2023
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30. Sex-stratified RNA-seq analysis reveals traumatic brain injury-induced transcriptional changes in the female hippocampus conducive to dementia
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Fiorini, Michael R., primary, Dilliott, Allison A., additional, and Farhan, Sali M. K., additional
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- 2022
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31. Novel regulatory logic in the antibiotic resistance response ofEnterococcus faecalisagainst cell envelope targeting antibiotics
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Sali M. Morris, Georg Fritz, Tim Rogers, and Susanne Gebhard
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SummaryEnterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope-acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two-component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. We here explored the interplay between these two regulatory pathways. Our results show the regulation by SapR of an additional resistance operon,dltXABCD, and show that LiaFSR regulates the expression ofsapRS, placing SapRS target genes under dual control:dltXABCDexpression depends on both antibiotic-induced cellular damage (LiaFSR)andthe presence of a substrate drug for the sensory transporter (SapAB). We further show that this network protectsE. faecalisfrom antimicrobials produced by potential competitor bacteria, providing a potential rationale for the evolution of this regulatory strategy. The network structure described here can explain why clinical DAP resistance often emerges via mutations in regulatory components, which may ultimately lead to the discovery of new therapeutic targets.Graphical abstract
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- 2022
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32. Novel regulatory logic in the antibiotic resistance response ofEnterococcus faecalisagainst cell envelope targeting antibiotics
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Morris, Sali M., primary, Fritz, Georg, additional, Rogers, Tim, additional, and Gebhard, Susanne, additional
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- 2022
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33. Cover Image, Volume 177B, Number 1, January 2018
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Farhan, Sali M. K., Gendron, Tania F., Petrucelli, Leonard, Hegele, Robert A., and Strong, Michael J.
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- 2018
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34. OPTN p.Met468Arg and ATXN2 intermediate length polyQ extension in families with C9orf72 mediated amyotrophic lateral sclerosis and frontotemporal dementia
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Farhan, Sali M. K., Gendron, Tania F., Petrucelli, Leonard, Hegele, Robert A., and Strong, Michael J.
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- 2018
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35. Exome sequencing identifies NFS1 deficiency in a novel Fe‐S cluster disease, infantile mitochondrial complex II/III deficiency
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Sali M. K. Farhan, Jian Wang, John F. Robinson, Piya Lahiry, Victoria M. Siu, Chitra Prasad, Jonathan B. Kronick, David A. Ramsay, C. Anthony Rupar, and Robert A. Hegele
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Autozygosity mapping ,Fe‐S proteins ,mitochondrial complex deficiency ,NFS1 ,whole‐exome sequencing. ,Genetics ,QH426-470 - Abstract
Abstract Iron‐sulfur (Fe‐S) clusters are a class of highly conserved and ubiquitous prosthetic groups with unique chemical properties that allow the proteins that contain them, Fe‐S proteins, to assist in various key biochemical pathways. Mutations in Fe‐S proteins often disrupt Fe‐S cluster assembly leading to a spectrum of severe disorders such as Friedreich's ataxia or iron‐sulfur cluster assembly enzyme (ISCU) myopathy. Herein, we describe infantile mitochondrial complex II/III deficiency, a novel autosomal recessive mitochondrial disease characterized by lactic acidemia, hypotonia, respiratory chain complex II and III deficiency, multisystem organ failure and abnormal mitochondria. Through autozygosity mapping, exome sequencing, in silico analyses, population studies and functional tests, we identified c.215G>A, p.Arg72Gln in NFS1 as the likely causative mutation. We describe the first disease in man likely caused by deficiency in NFS1, a cysteine desulfurase that is implicated in respiratory chain function and iron maintenance by initiating Fe‐S cluster biosynthesis. Our results further demonstrate the importance of sufficient NFS1 expression in human physiology.
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- 2014
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36. Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy
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Farhan, Sali M K, Nixon, Kevin C J, Everest, Michelle, Edwards, Tara N, Long, Shirley, Segal, Dmitri, Knip, Maria J, Arts, Heleen H, Chakrabarti, Rana, Wang, Jian, Robinson, John F, Lee, Donald, Mirsattari, Seyed M, Rupar, C Anthony, Siu, Victoria M, Poulter, Michael O, Hegele, Robert A, and Kramer, Jamie M
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- 2017
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37. Questioning the association of the STMN2 dinucleotide repeat with ALS
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Jay P. Ross, Fulya Akcimen, Calwing Liao, Dan Spiegelman, Ben Weisburd, Nicolas Dupré, Patrick A. Dion, Guy A. Rouleau, and Sali M. K. Farhan
- Abstract
Lowered expression of STMN2 is associated with TDP-43 pathology in amyotrophic lateral sclerosis (ALS). Recently, the number of dinucleotide CA repeats in an intron of the STMN2 gene was reported to be associated with increased risk for ALS. Here, we used a case-control cohort of whole genome sequencing (WGS) as well as WGS from populations in the gnomAD cohort to attempt to replicate this proposed association. We find that repeats well above the previously reported pathogenic threshold of 19 are commonly observed in unaffected individuals across different populations. Further, we did not observe an association between longer STMN2 CA repeats and ALS phenotype. In summary, our results do not support a role of STMN2 CA repeats towards ALS risk.DisclosuresNone to disclose
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- 2022
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38. Two-Period Study Results from a Large Italian Hospital Laboratory Attesting SARS-CoV-2 Variant PCR Assay Evolution
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Liotti, Flora Marzia, De Maio, Flavio, Ippoliti, Chiara, Santarelli, Giulia, Monzo, F. R., Sali, Michela, Santangelo, Rosaria, Ceccherini-Silberstein, F., Sanguinetti, Maurizio, Posteraro, Brunella, Liotti F. M., De Maio F., Ippoliti C., Santarelli G., Sali M. (ORCID:0000-0003-3609-2990), Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Posteraro B. (ORCID:0000-0002-1663-7546), Liotti, Flora Marzia, De Maio, Flavio, Ippoliti, Chiara, Santarelli, Giulia, Monzo, F. R., Sali, Michela, Santangelo, Rosaria, Ceccherini-Silberstein, F., Sanguinetti, Maurizio, Posteraro, Brunella, Liotti F. M., De Maio F., Ippoliti C., Santarelli G., Sali M. (ORCID:0000-0003-3609-2990), Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), and Posteraro B. (ORCID:0000-0002-1663-7546)
- Abstract
In keeping with the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 causative agent, PCR assays have been developed to rapidly detect SARS-CoV-2 variants, which have emerged since the first (Alpha) variant was identified. Based on specific assortment of SARS-CoV-2 spike-protein mutations (DH69/V70, E484K, N501Y, W152C, L452R, K417N, and K417T) among the major variants known to date, Seegene Allplex SARS-CoV-2 Variants I and Variants II assays have been available since a few months before the last (Omicron) variant became predominant. Using S gene next-generation sequencing (NGS) as the SARS-CoV-2 variant identification reference method, we assessed the results of SARS-CoV-2-positive nasopharyngeal swab samples from two testing periods, before (n = 288, using only Variants I) and after (n = 77, using both Variants I and Variants II) the appearance of Omicron. The Variants I assay allowed correct identification for Alpha (37/37), Beta/Gamma (28/ 30), or Delta (220/221) variant-positive samples. The combination of the Variants I and Variants II assays allowed correct identification for 61/77 Omicron variant-positive samples. While 16 samples had the K417N mutation undetected with the Variants II assay, 74/77 samples had both DH69/V70 and N501Y mutations detected with the Variants I assay. If considering only the results by the Variants I assay, 6 (2 Beta variant positive, 1 Delta variant positive, and 3 Omicron variant positive) of 365 samples tested in total provided incorrect identification. We showed that the Variants I assay alone might be more suitable than both the Variants I and Variants II assays to identify currently circulating SARS-CoV-2 variants. Inclusion of additional variant-specific mutations should be expected in the development of future assays.
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- 2022
39. Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function
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Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B. (ORCID:0000-0001-9155-3388), Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), Popolla V., Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B. (ORCID:0000-0001-9155-3388), Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), and Popolla V.
- Abstract
Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at
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- 2022
40. Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children
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Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Tredicine, Maria, Pereyra Boza, Maria Del Carmen, Camponeschi, C., Morello, Rosa, Zampino, Giuseppe, Brooks, A. E. S., Rende, M., Ria, Francesco, Sanguinetti, Maurizio, Delogu, Giovanni, Sali, Michela, Di Sante, Gabriele, Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), De Rose C., Tredicine M., Pereyra Boza M. D. C., Morello R., Zampino G. (ORCID:0000-0003-3865-3253), Ria F. (ORCID:0000-0002-8444-0307), Sanguinetti M. (ORCID:0000-0002-9780-7059), Delogu G. (ORCID:0000-0003-0182-8267), Sali M. (ORCID:0000-0003-3609-2990), Di Sante G. (ORCID:0000-0001-6608-3388), Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Tredicine, Maria, Pereyra Boza, Maria Del Carmen, Camponeschi, C., Morello, Rosa, Zampino, Giuseppe, Brooks, A. E. S., Rende, M., Ria, Francesco, Sanguinetti, Maurizio, Delogu, Giovanni, Sali, Michela, Di Sante, Gabriele, Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), De Rose C., Tredicine M., Pereyra Boza M. D. C., Morello R., Zampino G. (ORCID:0000-0003-3865-3253), Ria F. (ORCID:0000-0002-8444-0307), Sanguinetti M. (ORCID:0000-0002-9780-7059), Delogu G. (ORCID:0000-0003-0182-8267), Sali M. (ORCID:0000-0003-3609-2990), and Di Sante G. (ORCID:0000-0001-6608-3388)
- Abstract
Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to s
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- 2022
41. Anti CD20-based immunochemotherapy abolishes antibody response to Covid-19 mRNA vaccine in lymphoma patients vaccinated during active first line treatment
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Bellesi, Silvia, Sali, Michela, Maiolo, Maria Elisa, Pereyra Boza, Maria Del Carmen, Alma, Eleonora, Palucci, Ivana, Fatone, Federica, De Maio, Flavio, Viscovo, Marcello, D'Alo', Francesco, De Stefano, Valerio, Hohaus, Stefan, Sanguinetti, Maurizio, Bellesi S., Sali M. (ORCID:0000-0003-3609-2990), Maiolo E., Pereyra Boza M. D. C., Alma E., Palucci I., Fatone F., De Maio F., Viscovo M., D'Alo F. (ORCID:0000-0003-3576-8522), De Stefano V. (ORCID:0000-0002-5178-5827), Hohaus S. (ORCID:0000-0002-5534-7197), Sanguinetti M. (ORCID:0000-0002-9780-7059), Bellesi, Silvia, Sali, Michela, Maiolo, Maria Elisa, Pereyra Boza, Maria Del Carmen, Alma, Eleonora, Palucci, Ivana, Fatone, Federica, De Maio, Flavio, Viscovo, Marcello, D'Alo', Francesco, De Stefano, Valerio, Hohaus, Stefan, Sanguinetti, Maurizio, Bellesi S., Sali M. (ORCID:0000-0003-3609-2990), Maiolo E., Pereyra Boza M. D. C., Alma E., Palucci I., Fatone F., De Maio F., Viscovo M., D'Alo F. (ORCID:0000-0003-3576-8522), De Stefano V. (ORCID:0000-0002-5178-5827), Hohaus S. (ORCID:0000-0002-5534-7197), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
- Abstract
N/A
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- 2022
42. Short- and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 in utero or during the perinatal period: preliminary findings
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Buonsenso, Danilo, Costa, Simonetta, Giordano, Lucia, Priolo, Francesca, Colonna, A. T., Morini, S., Sbarbati, Martina, Pata, D., Acampora, Anna, Conti, Guido, Crudo, Fabrizio, Cantiani, Alessandro, Martina, Bianca Maria, Amorelli, Giulia Maria, Orazi, Lorenzo, Petrianni, Maria, Ricci, Daniela, Lanzone, Antonio, Sanguinetti, Maurizio, Cattani Franchi, Paola, Sali, Michela, Romeo, Domenico Marco Maurizio, Zampino, Giuseppe, Vento, Giovanni, Valentini, Piero, Buonsenso D., Costa S., Giordano L., Priolo F., Sbarbati M., Acampora A., Conti G. (ORCID:0000-0003-2565-4206), Crudo F., Cantiani A., Martina B. M., Amorelli G. M., Orazi L., Petrianni M., Ricci D., Lanzone A. (ORCID:0000-0003-4119-414X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Sali M. (ORCID:0000-0003-3609-2990), Romeo D. (ORCID:0000-0002-6229-1208), Zampino G. (ORCID:0000-0003-3865-3253), Vento G. (ORCID:0000-0002-8132-5127), Valentini P. (ORCID:0000-0001-6095-9510), Buonsenso, Danilo, Costa, Simonetta, Giordano, Lucia, Priolo, Francesca, Colonna, A. T., Morini, S., Sbarbati, Martina, Pata, D., Acampora, Anna, Conti, Guido, Crudo, Fabrizio, Cantiani, Alessandro, Martina, Bianca Maria, Amorelli, Giulia Maria, Orazi, Lorenzo, Petrianni, Maria, Ricci, Daniela, Lanzone, Antonio, Sanguinetti, Maurizio, Cattani Franchi, Paola, Sali, Michela, Romeo, Domenico Marco Maurizio, Zampino, Giuseppe, Vento, Giovanni, Valentini, Piero, Buonsenso D., Costa S., Giordano L., Priolo F., Sbarbati M., Acampora A., Conti G. (ORCID:0000-0003-2565-4206), Crudo F., Cantiani A., Martina B. M., Amorelli G. M., Orazi L., Petrianni M., Ricci D., Lanzone A. (ORCID:0000-0003-4119-414X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Sali M. (ORCID:0000-0003-3609-2990), Romeo D. (ORCID:0000-0002-6229-1208), Zampino G. (ORCID:0000-0003-3865-3253), Vento G. (ORCID:0000-0002-8132-5127), and Valentini P. (ORCID:0000-0001-6095-9510)
- Abstract
The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48–72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48–72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). Conclusions: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of
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- 2022
43. Comparative Fecal Microbiota Analysis of Infants With Acute Bronchiolitis Caused or Not Caused by Respiratory Syncytial Virus
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De Maio, Flavio, Buonsenso, Danilo, Bianco, D. M., Giaimo, M., Fosso, B., Monzo, F. R., Sali, Michela, Posteraro, Brunella, Valentini, Piero, Sanguinetti, Maurizio, De Maio F., Buonsenso D., Sali M. (ORCID:0000-0003-3609-2990), Posteraro B. (ORCID:0000-0002-1663-7546), Valentini P. (ORCID:0000-0001-6095-9510), Sanguinetti M. (ORCID:0000-0002-9780-7059), De Maio, Flavio, Buonsenso, Danilo, Bianco, D. M., Giaimo, M., Fosso, B., Monzo, F. R., Sali, Michela, Posteraro, Brunella, Valentini, Piero, Sanguinetti, Maurizio, De Maio F., Buonsenso D., Sali M. (ORCID:0000-0003-3609-2990), Posteraro B. (ORCID:0000-0002-1663-7546), Valentini P. (ORCID:0000-0001-6095-9510), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
- Abstract
Bronchiolitis due to respiratory syncytial virus (RSV) or non-RSV agents is a health-menacing lower respiratory tract (LRT) disease of infants. Whereas RSV causes more severe disease than other viral agents may, genus-dominant fecal microbiota profiles have been identified in US hospitalized infants with bronchiolitis. We investigated the fecal microbiota composition of infants admitted to an Italian hospital with acute RSV (25/37 [67.6%]; group I) or non-RSV (12/37 [32.4%]; group II) bronchiolitis, and the relationship of fecal microbiota characteristics with the clinical characteristics of infants. Group I and group II infants differed significantly (24/25 [96.0%] versus 5/12 [41.7%]; P = 0.001) regarding 90% oxygen saturation (SpO2), which is an increased respiratory effort hallmark. Accordingly, impaired feeding in infants from group I was significantly more frequent than in infants from group II (19/25 [76.0%] versus 4/12 [33.3%]; P = 0.04). Conversely, the median (IQR) length of stay was not significantly different between the two groups (seven [3–14] for group I versus five [5–10] for group II; P = 0.11). The 16S ribosomal RNA V3–V4 region amplification of infants’ fecal samples resulted in 299 annotated amplicon sequence variants. Based on alpha- and beta-diversity microbiota downstream analyses, group I and group II infants had similar bacterial communities in their samples. Additionally, comparing infants having <90% SpO2 (n = 29) with infants having ≥90% SpO2 (n = 8) showed that well-known dominant genera (Bacteroides, Bifidobacterium, Escherichia/Shigella, and Enterobacter/Veillonella) were differently, but not significantly (P = 0.44, P = 0.71, P = 0.98, and P = 0.41, respectively) abundant between the two subgroups. Overall, we showed that, regardless of RSV or non-RSV bronchiolitis etiology, no fecal microbiota-composing bacteria could be associated with the severity of acute bronchiolitis in infants. Larger and longitudinally conducted studies wil
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- 2022
44. 3D-printed graphene polylactic acid devices resistant to SARS-CoV-2: Sunlight-mediated sterilization of additive manufactured objects
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De Maio, Flavio, Rosa, Enrico, Perini, Giordano, Augello, A, Niccolini, Benedetta, Ciaiola, F, Santarelli, Giulia, Sciandra, Francesca, Bozzi, Manuela, Sanguinetti, Maurizio, Sali, Michela, De Spirito, Marco, Delogu, Giovanni, Palmieri, Valentina, Papi, Massimiliano, De Maio F, Rosa E, Perini G (ORCID:0000-0001-9452-8479), Niccolini B, Santarelli G, Sciandra F, Bozzi M (ORCID:0000-0002-2656-5849), Sanguinetti M (ORCID:0000-0002-9780-7059), Sali M (ORCID:0000-0003-3609-2990), De Spirito M (ORCID:0000-0003-4260-5107), Delogu G (ORCID:0000-0003-0182-8267), Palmieri V, Papi M (ORCID:0000-0002-0029-1309), De Maio, Flavio, Rosa, Enrico, Perini, Giordano, Augello, A, Niccolini, Benedetta, Ciaiola, F, Santarelli, Giulia, Sciandra, Francesca, Bozzi, Manuela, Sanguinetti, Maurizio, Sali, Michela, De Spirito, Marco, Delogu, Giovanni, Palmieri, Valentina, Papi, Massimiliano, De Maio F, Rosa E, Perini G (ORCID:0000-0001-9452-8479), Niccolini B, Santarelli G, Sciandra F, Bozzi M (ORCID:0000-0002-2656-5849), Sanguinetti M (ORCID:0000-0002-9780-7059), Sali M (ORCID:0000-0003-3609-2990), De Spirito M (ORCID:0000-0003-4260-5107), Delogu G (ORCID:0000-0003-0182-8267), Palmieri V, and Papi M (ORCID:0000-0002-0029-1309)
- Abstract
Additive manufacturing has played a crucial role in the COVID-19 global emergency allowing for rapid production of medical devices, indispensable tools for hospitals, or personal protection equipment. However, medical devices, especially in nosocomial environments, represent high touch surfaces prone to viral infection and currently used filaments for 3D printing can't inhibit transmission of virus [1]. Graphene-family materials are capable of reinforcing mechanical, optical and thermal properties of 3D printed constructs. In particular, graphene can adsorb near-infrared light with high efficiency. Here we demonstrate that the addition of graphene nanoplatelets to PLA filaments (PLA-G) allows the creation of 3D-printed devices that can be sterilized by near-infrared light exposure at power density analog to sunlight. This method has been used to kill SARS-CoV-2 viral particles on the surface of 3D printed PLA-G by 3 min of exposure. 3D-printed PLA-G is highly biocompatible and can represent the ideal material for the production of sterilizable personal protective equipment and daily life objects intended for multiple users.
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- 2022
45. Tsukamurella tyrosinosolvens and Rhizobium radiobacter sepsis presenting with septic pulmonary emboli
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Romano, L., Spanu, T., Calista, F., Zappacosta, B., Mignogna, S., Sali, M., Fiori, B., and Fadda, G.
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- 2011
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46. Questioning the association of the STMN2 dinucleotide repeat with ALS
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Ross, Jay P., primary, Akcimen, Fulya, additional, Liao, Calwing, additional, Spiegelman, Dan, additional, Weisburd, Ben, additional, Dupré, Nicolas, additional, Dion, Patrick A., additional, Rouleau, Guy A., additional, and Farhan, Sali M. K., additional
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- 2022
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47. DnaJC7 in Amyotrophic Lateral Sclerosis
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Dilliott, Allison A., primary, Andary, Catherine M., additional, Stoltz, Meaghan, additional, Petropavlovskiy, Andrey A., additional, Farhan, Sali M. K., additional, and Duennwald, Martin L., additional
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- 2022
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48. Questioning the Association of the
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Jay P, Ross, Fulya, Akçimen, Calwing, Liao, Dan, Spiegelman, Ben, Weisburd, Nicolas, Dupré, Patrick A, Dion, Guy A, Rouleau, and Sali M K, Farhan
- Abstract
Recently, the number of dinucleotide CA repeats in an intron of theHere, we used whole-genome sequencing and tested theWe find that repeats well above the previously reported pathogenic threshold of 19 are commonly observed in unaffected individuals across different populations. Furthermore, we did not observe an association between longerIn summary, our results do not support a role of
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- 2022
49. KMT2D p.Gln3575His segregating in a family with autosomal dominant choanal atresia strengthens the Kabuki/CHARGE connection
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Badalato, Lauren, Farhan, Sali M. K., Dilliott, Allison A., Bulman, Dennis E., Hegele, Robert A., and Goobie, Sharan L.
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- 2017
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50. Exome Sequencing: New Insights into Lipoprotein Disorders
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Farhan, Sali M. K. and Hegele, Robert A.
- Published
- 2014
- Full Text
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