156 results on '"Bruno, Claudio"'
Search Results
2. Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study.
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Chiriboga, Claudia A., Bruno, Claudio, Duong, Tina, Fischer, Dirk, Mercuri, Eugenio, Kirschner, Janbernd, Kostera-Pruszczyk, Anna, Jaber, Birgit, Gorni, Ksenija, Kletzl, Heidemarie, Carruthers, Imogen, Martin, Carmen, Warren, Francis, Scalco, Renata S., Wagner, Kathryn R., and Muntoni, Francesco
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SPINAL muscular atrophy , *RESPIRATORY infections - Abstract
Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Microlitiasi alveolare polmonare.
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Oliboni, Giancarlo, Bruno, Claudio, Giulianelli, Giacomo, and Nizzetto, Manuele
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Pulmonary Alveolar Microlithiasis (PAM) is a rare disease characterized by the intra-alveolar accumulation of calcium phosphate crystals. Currently, mutations in the SLC34A2 gene, encoding a sodium-dependent protein responsible for the transportation of phosphate ions from the alveolar space into alveolar type II cells, are believed to be the leading cause. We present a case of a 76-years old male with history of cough and recurrent bronchitis, initially treated with bronchodilator inhalers. After a chest X-ray done for a left basal pneumonia, a reticulonodular interstitial pattern emerged. This has been later described by chest CTs as a possible alveolar lithiasis. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases.
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Ardissone, Anna, Bruno, Claudio, Diodato, Daria, Donati, Alice, Ghezzi, Daniele, Lamantea, Eleonora, Lamperti, Costanza, Mancuso, Michelangelo, Martinelli, Diego, Primiano, Guido, Procopio, Elena, Rubegni, Anna, Santorelli, Filippo, Schiaffino, Maria Cristina, Servidei, Serenella, Tubili, Flavia, Bertini, Enrico, and Moroni, Isabella
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MITOCHONDRIA , *PROGNOSIS , *CENTRAL nervous system , *MITOCHONDRIAL pathology , *OXIDATIVE phosphorylation , *PROTEINS , *RESEARCH , *GENETIC mutation , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *RESEARCH funding , *LEIGH disease , *MEMBRANE proteins - Abstract
Background: Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database.Results: Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date.Conclusion: We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup. [ABSTRACT FROM AUTHOR]- Published
- 2021
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5. Novel compound heterozygous pathogenic variants in nucleotide-binding protein like protein (NUBPL) cause leukoencephalopathy with multi-systemic involvement.
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Protasoni, Margherita, Bruno, Claudio, Donati, Maria Alice, Mohamoud, Khadra, Severino, Mariasavina, Allegri, Anna, Robinson, Alan J., Reyes, Aurelio, Zeviani, Massimo, and Garone, Caterina
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SHORT stature , *PROTEINS , *DEVELOPMENTAL delay , *MITOCHONDRIAL DNA , *ANTISENSE DNA , *ALPHA 1-antitrypsin , *MITOCHONDRIAL pathology - Abstract
NUBPL (Nucleotide-binding protein like) protein encodes a member of the Mrp/NBP35 ATP-binding proteins family, deemed to be involved in mammalian complex I (CI) assembly process. Exome sequencing of a patient presenting with infantile-onset hepatopathy, renal tubular acidosis, developmental delay, short stature, leukoencephalopathy with minimal cerebellar involvement and multiple OXPHOS deficiencies revealed the presence of two novel pathogenic compound heterozygous variants in NUBPL (p.Phe242Leu/p.Leu104Pro). We investigated patient's and control immortalised fibroblasts and demonstrated that both the peripheral and the membrane arms of complex I are undetectable in mutant NUBPL cells, resulting in virtually absent CI holocomplex and loss of enzyme activity. In addition, complex III stability was moderately affected as well. Lentiviral-mediated expression of the wild-type NUBPL cDNA rescued both CI and CIII assembly defects, confirming the pathogenicity of the variants. In conclusion, this is the first report describing a complex multisystemic disorder due to NUBPL defect. In addition, we confirmed the role of NUBPL in Complex I assembly associated with secondary effect on Complex III stability and we demonstrated a defect of mtDNA-related translation which suggests a potential additional role of NUBPL in mtDNA expression. [ABSTRACT FROM AUTHOR]
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- 2020
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6. The chemosensitizing agent lubeluzole binds calmodulin and inhibits Ca2+/calmodulin-dependent kinase II.
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Bruno, Claudio, Cavalluzzi, Maria Maddalena, Rusciano, Maria Rosaria, Lovece, Angelo, Carrieri, Antonio, Pracella, Riccardo, Giannuzzi, Giulia, Polimeno, Lorenzo, Viale, Maurizio, Illario, Maddalena, Franchini, Carlo, and Lentini, Giovanni
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CALMODULIN , *CHEMORECEPTORS , *CAPILLARY electrophoresis , *METHYL aspartate receptors , *NEUROPROTECTIVE agents , *ANTINEOPLASTIC agents - Abstract
An affinity capillary electrophoresis (ACE) method to estimate apparent dissociation constants between bovine brain calmodulin (CaM) and non-peptidic ligands was developed. The method was validated reproducing the dissociation constants of a number of well-known CaM ligands. In particular, the potent antagonist 125-C9 was ad hoc synthesized through an improved synthetic procedure. The ACE method was successfully applied to verify CaM affinity for lubeluzole, a well-known neuroprotective agent recently proved useful to potentiate the activity of anti-cancer drugs. Lubeluzole was slightly less potent than 125-C9 ( K d = 2.9 ± 0.7 and 0.47 ± 0.06 μM, respectively) and displayed Ca 2+ /calmodulin-dependent kinase II (CaMKII) inhibition (IC 50 = 40 ± 1 μM). Possible binding modes of lubeluzole to CaM were explored by docking studies based on the X-ray crystal structures of several trifluoperazine-CaM complexes. An estimated dissociation constant in good agreement with the experimental one was found and the main aminoacidic residues and interactions contributing to complex formation were highlighted. The possibility that interference with Ca 2+ pathways may contribute to the previously observed chemosensitizing effects of lubeluzole on human ovarian adenocarcinoma and lung carcinoma cells are discussed. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Impact of multi-component diffusion in turbulent combustion using direct numerical simulations.
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Bruno, Claudio, Sankaran, Vaidyanathan, Kolla, Hemanth, and Chen, Jacqueline H.
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DIFFUSION , *TURBULENCE , *COMBUSTION , *COMPUTER simulation , *ATMOSPHERIC pressure , *FLAME - Abstract
This paper presents the results of DNS of a partially premixed turbulent syngas/air flame at atmospheric pressure. The objective was to assess the importance and possible effects of molecular transport on flame behavior and structure. To this purpose DNS were performed at with two proprietary DNS codes and with three different molecular diffusion transport models: fully multi-component, mixture averaged, and imposing the Lewis number of all species to be unity. Results indicate that 1. At the Reynolds numbers of the simulations ( Re turb = 600, Re = 8000) choice of molecular diffusion models affects significantly the temperature and concentration fields; 2. Assuming Le = 1 for all species predicts temperatures up to 250 K higher than the physically realistic multi-component model; 3. Faster molecular transport of lighter species changes the local concentration field and affects reaction pathways and chemical kinetics. A possible explanation for these observations is provided in terms of species diffusion velocity that is a strong function of gradients: thus, at sufficiently large Reynolds numbers, gradients and their effects tend to be large. The preliminary conclusion from these simulations seems to indicate molecular diffusion as the third important mechanism active in flames besides convective transport and kinetics. If confirmed by further DNS and measurements, molecular transport in high intensity turbulent flames will have to be realistically modeled to accurately predict emissions (gaseous and particulates) and other combustor performance metrics. [ABSTRACT FROM AUTHOR]
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- 2015
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8. Vaccination recommendations for patients with neuromuscular disease.
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Esposito, Susanna, Bruno, Claudio, Berardinelli, Angela, Filosto, Massimiliano, Mongini, Tiziana, Morandi, Lucia, Musumeci, Olimpia, Pegoraro, Elena, Siciliano, Gabriele, Tonin, Paola, Marrosu, Gianni, Minetti, Carlo, Servida, Maura, Fiorillo, Chiara, Conforti, Giorgio, Scapolan, Silvia, Ansaldi, Filippo, Vianello, Andrea, Castaldi, Silvana, and Principi, Nicola
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NEUROMUSCULAR diseases , *VACCINATION , *INFECTION prevention , *PREVENTIVE medicine , *VACCINE effectiveness , *DRUG tolerance , *IMMUNOCOMPROMISED patients , *PATIENTS - Abstract
Neuromuscular diseases (NMDs) encompass a broad spectrum of conditions. Because infections may be relevant to the final prognosis of most NMDs, vaccination appears to be the simplest and most effective solution for protecting NMD patients from vaccine-preventable infections. However, very few studies have evaluated the immunogenicity, safety, tolerability, and efficacy of different vaccines in NMD patients; therefore, detailed vaccination recommendations for NMD patients are not available. Here, we present vaccination recommendations from a group of Italian Scientific Societies for optimal disease prevention in NMD patients that maintain high safety levels. We found that NMD patients can be classified into two groups according to immune function: patients with normal immunity and patients who are immunocompromised, including those who intermittently or continuously take immunosuppressive therapy. Patients with normal immunity and do not take immunosuppressive therapy can be vaccinated as healthy subjects. In contrast, immunocompromised patients, including those who take immunosuppressive therapy, should receive all inactivated vaccines as well as influenza and pneumococcal vaccines; these patients should not be administered live attenuated vaccines. In all cases, the efficacy and long-term persistence of immunity from vaccination in NMD patients can be lower than in normal subjects. Household contacts of immunocompromised NMD patients should also be vaccinated appropriately. [ABSTRACT FROM AUTHOR]
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- 2014
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9. MRI in the diagnosis and surgical management of abnormal placentation.
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PALACIOS‐JARAQUEMADA, JOSÉ MIGUEL, BRUNO, CLAUDIO HERNÁN, and MARTÍN, EDUARDO
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PLACENTA abnormalities , *OPERATIVE surgery , *MAGNETIC resonance imaging , *FOLLOW-up studies (Medicine) , *HEALTH outcome assessment , *DIAGNOSIS - Abstract
Objective. To determine the usefulness of placental magnetic resonance imaging (MRI) in the diagnosis and surgical management of abnormal placentation. Design. Retrospective follow-up. Setting. Buenos Aires, Argentina. Population. 547 pregnant women. Methods. In all cases, a direct and reliable description of abnormal placentation features was obtained by the operating surgeon. Placental MRI was analyzed according to: (1) primary description, (2) invasion topography, (3) modification required to the surgical tactics or techniques and (4) by positive and negative predictive values. Main outcome measures. Ultrasound and MRI findings were compared with surgical results, which were considered a final diagnosis in relation to primary diagnostic indications. Results. Placental MRI was obtained because of diagnostic doubt in 78 cases, for deep invasion diagnosis in 148 cases and to define the invasion area in 346 cases. Placental MRI allowed accurate demarcation and assessment of the degree of placental invasion, parametrial involvement and cervico-trigonal vascular hyperplasia, permitting changes in the surgical tactical approach. Ultrasound and MRI differences were associated with placenta previa, uterine scar thinning and use of different criteria for placental invasion through definitions or terminology. Six cases of false-negative and 11 of false-positive findings were reported. Conclusion. Placental MRI provides excellent characterization of the degree and extension of placental invasion. Its usefulness in cases of adherent placentation is directly associated to the therapeutic measures, especially where dissection maneuvers are needed. Diagnostic differences between ultrasound and MRI related to the presence or not of placenta previa and uterine scar thinning. [ABSTRACT FROM AUTHOR]
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- 2013
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10. Microwave-Assisted Synthesis of (±)-Mandelic Acid-d5, Optical Resolution, and Absolute Configuration Determination.
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Bruno, Claudio, Lentini, Giovanni, Lovece, Angelo, Cavalluzzi, Maria Maddalena, Carocci, Alessia, Catalano, Alessia, and Franchini, Carlo
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CHEMICAL synthesis , *HYDROXY acids , *MICROWAVES , *RESOLUTION (Chemistry) , *SALT , *RACEMIC mixtures , *ELECTROPHORESIS , *CIRCULAR dichroism - Abstract
An efficient microwave-assisted synthesis of (±)-mandelic acid-d5 was developed. The racemic mixture was resolved by diastereomeric salt formation using 1-phenylethylamine enantiomers as resolving agents. At each step, the resolution process was checked by determining mandelic acid-d5 enantiomer ee values directly on fractional crystallized diastereomeric salts by chiral capillary electrophoresis analysis. Highly enriched (-)- and (+)-mandelic acid-d5 (95% and 90% ee, resp.) were obtained and their absolute configurations--R and S, respectively--were determined by correlation of the (-)-mandelic acid-d5 circular dichroism spectrum to the (R)-mandelic acid one. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII)
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Musumeci, Olimpia, Bruno, Claudio, Mongini, Tiziana, Rodolico, Carmelo, Aguennouz, M’hammed, Barca, Emanuele, Amati, Angela, Cassandrini, Denise, Serlenga, Luigi, Vita, Giuseppe, and Toscano, Antonio
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MUSCLE enzymes , *PHOSPHOFRUCTOKINASES , *GLYCOGEN storage disease type VII , *ENZYME deficiency , *MUSCLE cramps , *MYOGLOBINURIA , *MOLECULAR biology - Abstract
Abstract: Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen metabolism also known as glycogen storage disease type VII (GSDVII), is characterized by exercise intolerance, myalgias, cramps and episodic myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We studied five patients with PFKM deficiency coming from different Italian regions. All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria. One patient had a mild hypertrophic cardiomyopathy. Biochemical studies revealed residual PFK activity ranging from 1 to 5%. Molecular genetic analysis identified four novel mutations in the PFKM gene. In our series of patients, clinical and laboratory features were similar in all but one patient, who had an unusual phenotype characterized by 25years disease history, high CK levels, hypertrophic cardiomyopathy with paroxysmal atrial fibrillation without fixed muscle weakness. [Copyright &y& Elsevier]
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- 2012
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12. Mitochondrial myopathy in a child with a muscle-restricted mutation in the mitochondrial transfer RNAAsn gene
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Bruno, Claudio, Cassandrini, Denise, Fattori, Fabiana, Pedemonte, Marina, Fiorillo, Chiara, Brigati, Giorgia, Brisca, Giacomo, Minetti, Carlo, and Santorelli, Filippo M.
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MITOCHONDRIAL pathology , *GENETIC mutation , *TRANSFER RNA , *MUSCLE diseases , *HISTOCHEMISTRY , *DIFFERENTIAL diagnosis , *EXERCISE for children - Abstract
Abstract: We report an 11-year-old boy with exercise-related myopathy, and a novel mutation m.5669G>A in the mitochondrial tRNA Asparagine gene (mt-tRNAAsn, MTTN). Muscle biopsy studies showed COX-negative, SDH-positive fibers at histochemistry and biochemical defects of oxidative metabolism. The m.5669G>A mutation was present only in patient’s muscle resulting in the first muscle-specific MTTN mutation. Mt-tRNAAsn steady-state levels and in silico predictions supported the pathogenicity of this mutation. A mitochondrial myopathy should be considered in the differential diagnosis of exercise intolerance in children. [Copyright &y& Elsevier]
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- 2011
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13. Investigation of nuclear electric powered interstellar precursor missions
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Simone, Domenico, Bruno, Claudio, and Czysz, Paul A.
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ELECTRIC propulsion , *ASTROPHYSICS , *INTERPLANETARY medium , *ROCKET payloads , *MASS budget (Geophysics) - Abstract
Abstract: Nuclear Electric Propulsion (NEP) is a technology conceptually proposed since the 1940s by E. Stuhlinger in Germany. The JIMO mission originally planned by NASA in the early 2000s produced at least two designs of ion thrusters fed by a 20–30kW nuclear powerplant. When compared to conventional (chemical) propulsion, the major advantage of NEP in the JIMO context was recognized to be the much higher I sp (lab-tested at up to 15,000s) and the capability for sustained power generation, up to 8–10 years when derated to I sp about 8000s. The goal of this paper is to show that current or near term NEP technology enables missions far beyond our immediate interplanetary backyard. In fact, by extending the semi-analytical approach used by Stuhlinger, with reasonable ratios α≡power/mass of the propulsion system (i.e., 0.1– 0.4kW/kg), missions to the Kuiper Belt (40AU and beyond) and even the so-called FOCAL mission (at 540AU) become feasible with an attractive payload fraction and in times of order 10–15 years. Further results regarding missions to Sedna’s perihelion/aphelion, and to Oort’s cloud will also be presented, showing the constraints affecting their feasibility and mass budget. [Copyright &y& Elsevier]
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- 2011
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14. Physics and Regimes of Supersonic Combustion.
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Ingenito, Antonella and Bruno, Claudio
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COMBUSTION , *ULTRASONICS , *ENGINES , *EDDIES , *SCRAMJET engines - Abstract
Understanding the physics of supersonic combustion is the key to design a performing engine for scramjetpowered vehicles. Despite studies on supersonic combustion dating back to the 1950s, there are still numerous uncertainties and misunderstandings on this topic. The following questions need to be answered: How does compressibility affect mixing, flame anchoring, and combustion efficiency? How long must a combustor be to ensure complete mixing and combustion while avoiding prohibitive performance losses? How can reacting turbulent and compressible flows be modeled? Experimental results in the past have shown that supersonic combustion of hydrogen and air is feasible and takes place in a reasonable distance, which is a necessary requirement in actual hypersonic vehicles powered by supersonic combustion ramjets. These results are explained bused on a theoretical analysis of the physical mechanisms driving mixing and combustion in supersonic airstreams, where they are found to be different from those in the incompressible regime. In particular, the classic Kolmogorov scaling is shown to be no longer strictly valid, and the flame regime is predicted to be significantly affected by compressibility and different from that of subsonic flames. This analysis is also supported by the results of the numerical simulations presented, showing that by generating sufficiently intense turbulence, a supersonic combustion flame is short and can indeed anchor within a small distance from fuel injectors, with the flame typically burning in the so-called flamelets-ineddies regime. [ABSTRACT FROM AUTHOR]
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- 2010
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15. One-step synthesis of homochiral O-aryl and O-heteroaryl mandelic acids and their use as efficient 1H NMR chiral solvating agents
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Cavalluzzi, Maria Maddalena, Bruno, Claudio, Lentini, Giovanni, Lovece, Angelo, Catalano, Alessia, Carocci, Alessia, and Franchini, Carlo
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CHIRALITY , *CARBOXYLIC acids , *NUCLEAR magnetic resonance spectroscopy , *ARYLATION , *HYDROXYL group , *COPPER , *BENZENE , *AMINES - Abstract
Abstract: Job and Buchwald’s one-step copper-promoted arylation of hydroxyl groups was explored and modified so that it could be applied to the coupling of mandelic acid with several halobenzenes and haloheteroarenes. A number of new homochiral O-aryl and O-heteroaryl mandelic acids, generally presenting high enantiomeric purities, were obtained. Although yields were moderate at the best, ranging from 9% to 41%, the reaction was convenient enough to prepare new mandelic acid derivatives, some of which performed as efficient chiral solvating agents (CSAs) for the direct 1H NMR ee value determination of several clinically and pharmacologically relevant amines. [Copyright &y& Elsevier]
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- 2009
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16. Unclassified polysaccharidosis of the heart and skeletal muscle in siblings
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Schoser, Benedikt, Bruno, Claudio, Schneider, Hans-Christian, Shin, Yoon S., Podskarbi, Teodor, Goldfarb, Lev, Müller-Felber, Wolfgang, and Müller-Höcker, Josef
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CARDIAC catheterization , *CARDIOGRAPHY , *ELECTROCARDIOGRAPHY , *ELECTROKYMOGRAPHY - Abstract
Abstract: We describe a 15-year-old boy and his 19-year-old sister with progressive dilated cardiomyopathy and mild non-progressive proximal lower limb myopathy, secondary to the accumulation of amylopectin-like fibrillar glycogen, (polyglucosan) bodies, in heart and skeletal muscle. Evidence of idiopathic amylopectinosis or polysaccharidosis was demonstrated in heart and skeletal muscle tissue by histology, electron microscopy, biochemical, and genetic analysis. In both siblings the heart muscle stored PAS-positive, proteinase-k resistant and partly diastase resistant granulo-filamentous material, simulating polyglucosan bodies. Glycogen branching enzyme activity, and phosphofructokinase enzyme activity, measured in skeletal muscle tissue and explanted heart tissue were all within the normal limits, however glycogen content was elevated. Furthermore, GBE1, PRKAG2, desmin, αβ-crystallin, ZASP, myotilin, and LAMP-2 gene sequencing revealed no mutation, excluding e.g. glycogen storage disease type 4 and desmin-related myofibrillar cardiomyopathies. In both patients the diagnosis of an idiopathic polysaccharidosis with progressive dilated cardiomyopathy was made, requiring heart transplantation at age 13 and 14, respectively. Both patients belong to an autosomal recessive group of biochemically and genetically unclassified severe vacuolar glycogen storage disease of the heart and skeletal muscle. Up to now unidentified glycogen synthesis or glycogen degradation pathways are supposed to contribute to this idiopathic glycogen storage disease. [Copyright &y& Elsevier]
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- 2008
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17. Clinical and genetic characterization of Chanarin–Dorfman syndrome
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Bruno, Claudio, Bertini, Enrico, Di Rocco, Maja, Cassandrini, Denise, Ruffa, Giuseppe, De Toni, Teresa, Seri, Marco, Spada, Marco, Li Volti, Giovanni, D’Amico, Adele, Trucco, Federica, Arca, Marcello, Casali, Carlo, Angelini, Corrado, DiMauro, Salvatore, and Minetti, Carlo
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GENETIC mutation , *BIOLOGICAL variation , *GENETICS , *MUSCLE diseases - Abstract
Abstract: We describe the clinical features, muscle pathology features, and molecular studies of seven patients with Chanarin–Dorfman syndrome (CDS) or neutral lipid storage disease and ichthyosis (NLSDI), a multisystem triglyceride storage disease with massive accumulation of lipid droplets in muscle fibers. All patients presented with congenital ichthyosiform erythroderma, cytoplasmic lipid droplets in blood cells, mild to severe hepatomegaly, and increased serum CK levels and liver enzymes. Three patients showed muscle symptoms and three had steathorrea. Molecular analysis identified five mutations, three of which are novel. These findings expand the clinical and mutational spectrum and underline the genetic heterogeneity of this disease. [Copyright &y& Elsevier]
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- 2008
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18. Adult polyglucosan body disease: Proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene.
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Massa, Roberto, Bruno, Claudio, Martorana, Alessandro, de Stefano, Nicola, van Diggelen, Otto P., and Federico, Antonio
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Adult polyglucosan body disease (APBD) is characterized by the accumulation of insoluble glucose polymers within the central and peripheral nervous systems. A common missense mutation in the glycogen branching enzyme ( GBE1) gene has been identified in Ashkenazi patients with APBD. We report on a non-Jewish patient with APBD on whom we performed proton magnetic resonance spectroscopic imaging of the brain. GBE activity in fibroblasts was markedly reduced, and a novel heterozygous mutation was identified in the GBE1 gene. Our findings widen the spectrum of APBD genotypes, underline the importance of performing GBE analysis in all APBD patients, and suggest that brain white matter degeneration in APBD may result from tissue damage involving axons and myelin. Muscle Nerve, 2007 [ABSTRACT FROM AUTHOR]
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- 2008
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19. Magnetic resonance imaging in 300 cases of placenta accreta: surgical correlation of new findings.
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Jaraquemada, JosÉ M. Palacios and Bruno, Claudio H.
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MAGNETIC resonance imaging , *PLACENTA diseases , *PREGNANCY complications , *SURGERY , *DIAGNOSTIC imaging , *NONINVASIVE diagnostic tests - Abstract
Background. To establish the usefulness of placental magnetic resonance in patients with a diagnosis of placenta accreta through the correlation of diagnostic images and surgical findings. Methods. Three hundred patients with ultrasound signs of placenta accreta were studied. In 252 patients, magnetic resonance imaging (MRI) was performed in a closed 1.5 T-resonator, and in 48 patients, open 0.23 T-set was used. T1 and T2 slices in the three planes were performed, and placental invasion was classified in depth levels and topographic areas in relation to the posterior vesical wall. The final degree of invasion was established during surgery according to clinical and anatomical criteria. The information obtained with MRI was analyzed, thus establishing its relevance to the change in surgical technique. Results. In 286 cases, MRI provided topographic information of placental invasion, and in 90 patients, it modified invasion levels. Undiagnosed parametrium extent was determined in ii cases, and 11 other cases were reclassified as placenta previa. Changes in conduct following MRI study included: recommendation to modify surgery date at week 35, recommendation for prophylactic ureteral catheterization, recommendation for the use of intraoperative blood salvage, possibility of approach through Pfannenstiel incision, probability of segmental myometrial approach, probability of aortic clamping, need to investigate subclinical disseminated intravascular coagulation, need of posterior pelvic dissection, and the possibility of uterine conservation. Conclusions. Magnetic resonance imaging turned out to be essential to define the topography and area of placental invasion. New findings modified surgical tactic and technique, allowing a reduction in historical morbidity and a significant increase in conservative surgeries. [ABSTRACT FROM AUTHOR]
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- 2005
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20. Mission to Mars using integrated propulsion concepts: considerations, opportunities, and strategies
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Accettura, Antonio G., Bruno, Claudio, Casotto, Stefano, and Marzari, Francesco
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MARTIAN exploration , *PROPULSION of space shuttles , *FEASIBILITY studies - Abstract
The aim of this paper is to evaluate the feasibility of a mission to Mars using the Integrated Propulsion Systems (IPS) which means to couple Nuclear-MPD-ISPU propulsion systems. In particular both mission analysis and propulsion aspects are analyzed together with technological aspects.Identifying possible mission scenarios will lead to the study of possible strategies for Mars Exploration and also of methods for reducing cost.As regard to IPS, the coupling between Nuclear Propulsion (Rubbia''s engine) and Superconductive MPD propulsion is considered for the Earth–Mars trajectories: major emphasis is given to the advantages of such a system. The In Situ Resource Utilization (ISRU) concerns on-Mars operations; In Situ Propellant Utilization (ISPU) is foreseen particularly for LOX-CH4 engines for Mars Ascent Vehicles and this possibility is analyzed from a technological point of view. Tether Systems are also considered during interplanetary trajectories and as space elevators on Mars orbit.Finally strategic considerations associated to this mission are considered also. [Copyright &y& Elsevier]
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- 2004
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21. Mitochondrial Myopathy and Respiratory Failure Associated With a New Mutation in the Mitochondrial Transfer Ribonucleic Acid Glutamic Acid Gene.
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Bruno, Claudio, Sacco, Oliviero, Santorelli, Filippo M., Assereto, Stefania, Tonoli, Emmanuel, Bado, Massimo, Rossi, Giovanni A., and Minetti, Carlo
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RESPIRATORY insufficiency , *MUSCLE diseases , *TRANSFER RNA , *GENES , *GENETIC mutation - Abstract
We report a novel T14687C mutation in the mitochondrial transfer ribonucleic acid glutamic acid gene in a 16-year-old boy with myopathy and lactic acidosis, retinopathy, and progressive respiratory failure leading to death. A muscle biopsy showed cytochrome c oxidase-negative ragged-red fibers, and biochemical analysis of the respiratory chain enzymes in muscle homogenate revealed complex I and complex IV deficiencies. The mutation, which affects the trinucleotide (TVC) loop, was nearly homoplasmic in the muscle DNA of the proband, but it was absent in his blood and in the blood from the asymptomatic mother, suggesting that it may have been a spontaneous somatic mutation in muscle. (J Child Neurol 2003;18:300-303). [ABSTRACT FROM AUTHOR]
- Published
- 2003
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22. A Novel Mutation in the SURF1 Gene in a Child With Leigh Disease, Peripheral Neuropathy, and Cytochrome-c Oxidase Deficiency.
- Author
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Bruno, Claudio, Biancheri, Roberta, Garavaglia, Barbara, Biedi, Claudia, Rossi, Andrea, Lamba, Laura Doria, Bado, Massimo, Greco, Marilena, Zeviani, Massimo, and Minetti, Carlo
- Subjects
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GENETIC disorders in children , *GENETIC mutation , *NEURODEGENERATION - Abstract
We report a 16-month-old boy with psychomotor regression, muscle hypotonia, peripheral neuropathy, and lactic acidosis. Brain magnetic resonance imaging showed a bilateral abnormal signal in the substantia nigra and in the subthalamic nucleus, suggestive of Leigh disease. Histochemical analysis of skeletal muscle showed decreased cytochromec oxidase activity. Biochemical analysis of respiratory chain enzymes in muscle homogenate and in cultured fibroblasts showed isolated cytochrome-c oxidase deficiency. Western blot analysis in fibroblasts showed the absence of Surf1 protein. Genetic analysis of the SURF1 gene revealed that the patient was compound heterozygous for a previously reported mutation at the splice-junction site of intron 3 (240 + 1G > T), and for a novel 4-bp deletion in exon 6 (531_534de1AAAT). Our data further enlarge the spectrum of mutations in SURF1 gene in patients with Leigh disease and cytochrome-c oxidase deficiency, contributing to better characterization of the clinical and neuroradiologic features of this group of patients for genotype-phenotype correlations. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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23. Some Key Issues in Hypersonic Propulsion.
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Bruno, Claudio and Ingenito, Antonella
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BRAYTON cycle , *VORTEX motion , *KINETIC energy , *THRUST , *SCRAMJET engines - Abstract
This paper summarizes and discusses some critical aspects of flying hypersonically. The first is the L/D (lift over drag) ratio determining thrust and that in turn depends on the slenderness Küchemann's τ parameter. This second parameter is found to depend on the relative importance of wave versus friction drag. Ultimately, all engineering drag is argued to depend on vorticity formed at the expense of the vehicle kinetic energy, thus requiring work by thrust. Different mixing strategies are discussed and shown to depend also on mechanisms forming vorticity when the regime is compressible. Supersonic combustion is briefly analyzed and found, at sufficiently high combustor Mach, to take place locally at constant volume, unlike conventional Brayton cycles. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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24. Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy.
- Author
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Alonso-Pérez, Jorge, González-Quereda, Lidia, Bruno, Claudio, Panicucci, Chiara, Alavi, Afagh, Nafissi, Shahriar, Nilipour, Yalda, Zanoteli, Edmar, Isihi, Lucas Michielon de Augusto, Melegh, Béla, Hadzsiev, Kinga, Muelas, Nuria, Vílchez, Juan J, Dourado, Mario Emilio, Kadem, Naz, Kutluk, Gultekin, Umair, Muhammad, Younus, Muhammad, Pegorano, Elena, and Bello, Luca
- Subjects
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FACIOSCAPULOHUMERAL muscular dystrophy , *MUSCULAR dystrophy , *LIMB-girdle muscular dystrophy , *GENE expression , *NEUROMUSCULAR diseases , *MUSCLE weakness , *MUSCULAR dystrophy diagnosis , *CYTOSKELETAL proteins , *RETROSPECTIVE studies , *RESEARCH funding - Abstract
Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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25. Unusual presentation of phosphoglycerate mutase deficiency due to two different mutations in PGAM-M gene
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Tonin, Paola, Bruno, Claudio, Cassandrini, Denise, Savio, Chiara, Tavazzi, Eleonora, Tomelleri, Giuliano, and Piccolo, Giovanni
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MUSCLE diseases , *GENETIC mutation , *MYALGIA , *MYOGLOBINURIA , *DIZZINESS , *SYNCOPE , *GLYCOGEN storage disease , *GENETICS - Abstract
Abstract: Phosphoglycerate mutase (PGAM) deficiency causes a rare metabolic myopathy characterized by exercise-related myalgia and myoglobinuria. This disorder was described in 13 patients and five different mutations in the PGAM-M gene were identified. We report on a new patient with an unusual clinical presentation. As a youth, he participated in different sports without complaining of muscular symptoms, but at 44years of age, after a brief, intense effort, he experienced lightheadedness without fainting. Serum CK was elevated and the ischemic exercise test showed a pathological lactate response. Muscle biopsy showed only mild abnormalities, but biochemical study revealed a defect of PGAM and genetic analysis showed two different mutations in the PGAM-M gene. Our case expands the clinical spectrum of PGAM deficiency and suggests that the frequency of this metabolic myopathy may be underestimated. [Copyright &y& Elsevier]
- Published
- 2009
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26. Two new mutations in the myophosphorylase gene in Italian patients with McArdle's disease
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Bruno, Claudio, Lanzillo, Roberta, Biedi, Claudia, Iadicicco, Lucia, Minetti, Carlo, and Santoro, Lucio
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PHOSPHORYLASES , *GENETIC mutation , *MUSCLE diseases - Abstract
We report two new mutations in the myophosphorylase gene (PYGM) in two unrelated Italian patients with myophosphorylase deficiency (McArdle''s disease). In one, we identified a missense C-to-T mutation at codon 269 in exon 7, changing CGA (arginine) to TGA (stop codon) (R269X). The second patient carried a G-to-C mutation, changing GCT (alanine) to CCT (proline) at codon 686 (A686P) in exon 17. Both were compound heterozygous, with the common mutation at codon 49 (R49X) on the other allele.Our data further expand the genetic heterogeneity in patients with McArdle''s disease, suggesting that the possibility of novel mutations has to be taken into account when performing genetic analysis in distinct ethnic groups. [Copyright &y& Elsevier]
- Published
- 2002
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27. Structured Light Plethysmography for Non-Invasive Assessment of Respiratory Pattern in Spinal Muscular Atrophy Type 1.
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Brolatti, Noemi, Trucco, Federica, Ferretti, Marta, Avanti, Chiara, Tacchetti, Paola, Panicucci, Chiara, Striano, Pasquale, Minetti, Carlo, Bruno, Claudio, and Pedemonte, Marina
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SPINAL muscular atrophy , *PLETHYSMOGRAPHY , *SUPINE position , *RESPIRATORY insufficiency - Abstract
Background: Spinal muscular atrophy (SMA) type 1 is a severe condition leading to early respiratory failure. Treatment options have become available, yet respiratory outcome measures in SMA type 1 are limited. The aim of this study was to assess the respiratory pattern in SMA type 1 patients via structured light plethysmography (SLP). SLP measures the thoraco-abdominal movements by projecting a light grid onto the anterior thoraco-abdominal surface. Methods: Cross-sectional study of consecutive children with SMA type 1. All children underwent motor assessment (CHOP-INTEND) and one-minute tidal breathing recording by SLP in supine position while self-ventilating in room air. The Respiratory rate, the abdominal vs. chest contribution to breath (Relative Expired Abdomen%, Relative Expired Chest%) and the severity of thoraco-abdominal paradox (Phase Angle) were acquired. Results: Nineteen patients were included, median (IQR) age 2.3 years (1.4–7.9). Their respiratory pattern captured via SLP showed a raised median (IQR) respiratory rate per age of 33.5 bpm (26.6–41.7), a prevalent abdominal contribution to tidal breathing with median (IQR) Relative Expired Abdomen 77% (68–90) vs. Chest 23% (10–32). Thoracoabdominal paradox was detected (median Phase Angle 48.70°) and its severity correlated negatively with CHOP-INTEND (r −0.8, p < 0.01). Conclusions: SLP captured and quantified the respiratory features of infants and children with SMA type 1. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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28. Clinical Phenotype of Pediatric and Adult Patients With Spinal Muscular Atrophy With Four SMN2 Copies: Are They Really All Stable?
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Ricci, Martina, Cicala, Gianpaolo, Capasso, Anna, Coratti, Giorgia, Fiori, Stefania, Cutrona, Costanza, D'Amico, Adele, Sansone, Valeria A., Bruno, Claudio, Messina, Sonia, Mongini, Tiziana, Coccia, Michela, Siciliano, Gabriele, Pegoraro, Elena, Masson, Riccardo, Filosto, Massimiliano, Comi, Giacomo P., Corti, Stefania, Ronchi, Dario, and Maggi, Lorenzo
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SPINAL muscular atrophy , *NATURAL history , *PHENOTYPES , *PHENOTYPIC plasticity , *ASYMPTOMATIC patients - Abstract
Objective: The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies. Methods: Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA). Results: The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow‐up = 36.9 ± 19 years). Six of the 169 patients were presymptomatic, 8 were classified as type II, 145 as type III (38 type IIIA and 107 type IIIB), and 8 as type IV. The remaining 2 patients were asymptomatic adults identified because of a familial case. The cross‐sectional functional data showed a reduction of scores with increasing age. Over 35% of the type III and 25% of the type IV lost ambulation (mean age = 26.8 years ± 16.3 SD). The risk of loss of ambulation was significantly associated with SMA type (p < 0.0001), with patients with IIIB and IV less likely to lose ambulation compared to type IIIA. There was an overall gender effect with a smaller number of women and a lower risk for women to lose ambulation. This was significant in the adult (p = 0.009) but not in the pediatric cohort (p = 0.43). Interpretation: Our results expand the existing literature on natural history of 4 SMN2 copies confirming the variability of phenotypes in untreated patients, ranging from type II to type IV and an overall reduction of functional scores with increasing age. ANN NEUROL 2023;94:1126–1135 [ABSTRACT FROM AUTHOR]
- Published
- 2023
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29. Early Muscle MRI Findings in a Pediatric Case of Emery-Dreifuss Muscular Dystrophy Type 1.
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Panicucci, Chiara, Casalini, Sara, Traverso, Monica, Brolatti, Noemi, Baratto, Serena, Raffaghello, Lizzia, Pedemonte, Marina, Doglio, Luca, Derchi, Maria, Tasca, Giorgio, Damasio, Beatrice M., Fiorillo, Chiara, and Bruno, Claudio
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- *
MUSCULAR dystrophy , *MAGNETIC resonance imaging , *ARTHROGRYPOSIS , *MUSCLE weakness , *FRAMESHIFT mutation , *CYTOPLASMIC inheritance , *FACIOSCAPULOHUMERAL muscular dystrophy - Abstract
Emery-Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early contractures, progressive muscle weakness, and cardiac abnormalities. Different subtypes of EDMD have been described, with the two most common forms represented by the X-linked EDMD1, caused by mutations in the EMD gene encoding emerin, and the autosomal EDMD2, due to mutations in the LMNA gene encoding lamin A/C. A clear definition of the magnetic resonance imaging (MRI) pattern in the two forms, and especially in the rarer EDMD1, is still lacking, although a preferential involvement of the medial head of the gastrocnemius has been suggested in EDMD2. We report a 13-year-old boy with mild limb girdle muscle weakness, elbow and ankle contractures, with absence of emerin at muscle biopsy, carrying a hemizygous frameshift mutation on the EMD gene (c.153dupC/p.Ser52Glufs*9) of maternal inheritance. Minor cardiac rhythm abnormalities were detected at 24-hour Holter electrocardiogram and required β-blocker therapy. MRI scan of the thighs showed a mild diffuse involvement, while tibialis anterior, extensor digitorum longus, peroneus longus, and medial gastrocnemius were the most affected muscles in the leg. We also provide a review of the muscular MRI data in EDMD patients and highlight the relative heterogeneity of the MRI patterns found in EDMDs, suggesting that muscle MRI should be studied in larger EDMD cohorts to better define disease patterns and to cover the wide disease spectrum. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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30. Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC registry).
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Pinós, Tomàs, Andreu, Antoni L., Bruno, Claudio, Hadjigeorgiou, Georgios M., Haller, Ronald G., Laforêt, Pascal, Lucía, Alejandro, Martín, Miguel A., Martinuzzi, Andrea, Navarro, Carmen, Oflazer, Piraye, Pouget, Jean, Quinlivan, Ros, Sacconi, Sabrina, Scalco, Renata S., Toscano, Antonio, Vissing, John, Vorgerd, Matthias, Wakelin, Andrew, and Martí, Ramon
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MEDICAL registries , *MEDICAL personnel as patients , *MUSCLE diseases , *GLYCOGEN storage disease , *MOLECULAR genetics - Abstract
Background: International patient registries are of particular importance for rare disorders, as they may contribute to overcome the lack of knowledge derived from low number of patients and limited awareness of these diseases, and help to learn more about their geographical or population-based specificities, which is relevant for research purposes and for promoting better standards of care and diagnosis. Our objective was to create and implement a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) and to disseminate the knowledge of these disorders.Results: Teams from nine different countries (United Kingdom, Spain, Italy, France, Germany, Denmark, Greece, Turkey and USA) created a consortium that developed the first European registry dedicated to rare muscle glycogenoses. A work plan was implemented to design the database and platform that constitute the registry, by choosing clinical, genetics and molecular variables of interest, based on experience gained from previous national registries for similar metabolic disorders. Among dissemination activities, several teaching events were organized in different countries, especially those where the consortium considered the awareness of these diseases needs to be promoted among health professionals and patients.Conclusion: EUROMAC represents a step forward in the knowledge of those disorders to which it is dedicated, and will have relevant clinical outcomes at the diagnostic, epidemiological, clinical and research level. [ABSTRACT FROM AUTHOR]- Published
- 2020
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31. Study Design of STR1VE-EU, a Phase 3 Trial of AVXS-101 Gene-Replacement Therapy (GRT) in Patients With Spinal Muscular Atrophy Type 1 (SMA1) in Europe.
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Muntoni, Francesco, Baranello, Giovanni, Bruno, Claudio, Corti, Stefania, Masson, Riccardo, Straub, Volker, Vita, Giuseppe, Ernst, Uwe, Kernbauer, Elaine, Williamson, Susan, Ouyang, Haojun, Feltner, Douglas E., Meriggioli, Matthew, Lavrov, Arseniy, L'Italien, James, Sproule, Douglas M., and Mercuri, Eugenio
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SPINAL muscular atrophy , *MOTOR neurons - Published
- 2019
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32. Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells.
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Cardone, Nastasia, Taglietti, Valentina, Baratto, Serena, Kefi, Kaouthar, Periou, Baptiste, Gitiaux, Ciryl, Barnerias, Christine, Lafuste, Peggy, Pharm, France Leturcq, Pharm, Juliette Nectoux, Panicucci, Chiara, Desguerre, Isabelle, Bruno, Claudio, Authier, François-Jerome, Fiorillo, Chiara, Relaix, Frederic, and Malfatti, Edoardo
- Abstract
Duchenne muscular dystrophy (DMD) is a devastating X-linked muscular disease, caused by mutations in the DMD gene encoding Dystrophin and affecting 1:5000 boys worldwide. Lack of Dystrophin leads to progressive muscle wasting and degeneration resulting in cardiorespiratory failure. Despite the absence of a definitive cure, innovative therapeutic avenues are emerging. Myopathologic studies are important to further understand the biological mechanisms of the disease and to identify histopathologic benchmarks for clinical evaluations. We conducted a myopathologic analysis on twenty-four muscle biopsies from DMD patients, with particular emphasis on regeneration, fibro-adipogenic progenitors and muscle stem cells behavior. We describe an increase in content of fibro-adipogenic progenitors, central orchestrators of fibrotic progression and lipid deposition, concurrently with a decline in muscle regenerative capacity. This regenerative impairment strongly correlates with compromised activation and expansion of muscle stem cells. Furthermore, our study uncovers an early acquisition of a senescence phenotype by DMD-afflicted muscle stem cells. Here we describe the myopathologic trajectory intrinsic to DMD and establish muscle stem cell senescence as a pivotal readout for future therapeutic interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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33. The Crystal Structure of N-[(2E)-3-(4-Chlorophenyl)prop-2-en-1-yl]-4-methoxy-N-methylbenzenesulfonamide.
- Author
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Carrozzini, Benedetta, Belviso, Benny Danilo, Bruno, Claudio, Cavalluzzi, Maria Maddalena, Lovece, Angelo, Lentini, Giovanni, and Caliandro, Rocco
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MONOCLINIC crystal system , *CRYSTAL structure , *UNIT cell , *SPACE groups , *PROTEIN kinases - Abstract
The title compound C17H18ClNO3S crystallizes in the monoclinic P21/c space group with unit cell parameters a = 15.040 (3) Å, b = 9.151 (6) Å, c = 13.868 (7) Å, β = 116.38 (5)°. Chlorophenyl and methoxyphenyl ring planes are approximately perpendicular and the two moieties form an angle of 82.2°. The crystal packing is stabilized by π–π and Cl–π interactions, which occur between parallel methoxyphenyl and chlorophenyl moieties. Dipolar intermolecular contacts, mainly involving the oxygen atoms and C–H, also contribute to the crystal network. The title compound is formed in the synthetic route for the production of potent inhibitors of calmodulin. Its crystal structure shows the chlorophenyl and methoxyphenyl moieties forming an angle of 82.2°. The crystal packing is stabilized by π–π, Cl–π and dipolar intermolecular contacts. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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34. Type I spinal muscular atrophy patients treated with nusinersen: 4‐year follow‐up of motor, respiratory and bulbar function.
- Author
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Pane, Marika, Coratti, Giorgia, Sansone, Valeria A., Messina, Sonia, Catteruccia, Michela, Bruno, Claudio, Sframeli, Maria, Albamonte, Emilio, Pedemonte, Marina, Brolatti, Noemi, Mizzoni, Irene, D'Amico, Adele, Bravetti, Chiara, Berti, Beatrice, Palermo, Concetta, Leone, Daniela, Salmin, Francesca, De Sanctis, Roberto, Pera, Maria Carmela, and Piastra, Marco
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SPINAL muscular atrophy , *NEUROMUSCULAR diseases , *CHILDREN'S hospitals , *NUTRITIONAL status - Abstract
Background: We report the 4‐year follow‐up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. Methods: The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE‐II). Results: Forty‐eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE‐II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2–4 years, 5–11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE‐2 increased significantly in patients younger than 2 years at treatment. In a mixed‐model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. Conclusions: Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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35. Recurrent Sensory-Motor Neuropathy Mimicking CIDP as Predominant Presentation of PDH Deficiency.
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Croci, Carolina, Cataldi, Matteo, Baratto, Serena, Bruno, Claudio, Trucco, Federica, Doccini, Stefano, Romano, Alessandro, Nesti, Claudia, Santorelli, Filippo Maria, and Fiorillo, Chiara
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- *
POLYNEUROPATHIES , *GLUCOSE-6-phosphate dehydrogenase deficiency , *CHRONIC inflammatory demyelinating polyradiculoneuropathy , *PYRUVATE dehydrogenase complex , *PERIPHERAL nervous system , *HEREDITY , *NEUROPATHY - Abstract
Introduction Pyruvate dehydrogenase complex (PDH) deficiency (Online Mendelian Inheritance in Man # 312170) is a relatively common mitochondrial disorder, caused by mutations in the X-linked PDHA1 gene and presenting with a variable phenotypic spectrum, ranging from severe infantile encephalopathy to milder chronic neurological disorders. Isolated peripheral neuropathy as predominant clinical presentation is uncommon. Results We report on a patient, now 21 years old, presenting at the age of 2 years with recurrent symmetric weakness as first symptom of a PDH deficiency. Neurophysiological evaluation proving a sensory-motor polyneuropathy with conduction blocks and presence of elevated cerebrospinal fluid proteins, suggested a chronic inflammatory demyelinating polyneuropathy. The evidence of high serum lactate and the alterations in oxidative metabolism in muscle biopsy pointed toward the final diagnosis. After starting nutritional supplements, no further episodes occurred. A hemizygous mutation in PDHA1 (p.Arg88Cys) was identified. This mutation has been previously described in five patients with a similar phenotype. A three-dimensional reconstruction demonstrated that mutations affecting this arginine destabilize the interactions between the subunits of the E1 complex. Conclusion We summarize the clinical and genetic characteristics of one patient with PDH deficiency presenting isolated peripheral nervous system involvement. This study highlights that the diagnosis of PDH deficiency should be considered in children with unexplained peripheral neuropathy, even with features suggestive of acquired forms, especially in case of early onset and limited response to treatment. A simple analysis of lactic acid could help to target the diagnosis. In addition, we suggest that the residue Arg88 is the most frequently involved in this specific phenotype of PDH deficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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36. Long-term clinical and MRI follow-up in two POMT2-related limb girdle muscular dystrophy (LGMDR14) patients.
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Panicucci, Chiara, Casalini, Sara, Damasio, Beatrice M., Brolatti, Noemi, Pedemonte, Marina, Biolcati Rinaldi, Alessandra, Morando, Simone, Doglio, Luca, Raffaghello, Lizzia, Fiorillo, Chiara, Zara, Federico, Tasca, Giorgio, and Bruno, Claudio
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MUSCULAR dystrophy , *MAGNETIC resonance imaging , *PELVIC bones , *FACIOSCAPULOHUMERAL muscular dystrophy , *BRAIN abnormalities , *NATURAL history - Abstract
POMT2-related limb girdle muscular dystrophy (LGMDR14) is a rare muscular dystrophy caused by mutations in the POMT2 gene. Thus far only 26 LGMDR14 subjects have been reported and no longitudinal natural history data are available. We describe two LGMDR14 patients followed for 20 years since infancy. Both patients presented a childhood-onset, slowly progressive pelvic girdle muscular weakness leading to loss of ambulation in the second decade in one patient, and cognitive impairment without detectable brain structural abnormalities. Glutei, paraspinal, and adductor muscles were the primarily involved muscles at MRI. This report provides natural history data on LGMDR14 subjects, with a focus on longitudinal muscle MRI. We also reviewed the LGMDR14 literature data, providing information on the LGMDR14 disease progression. Considering the high prevalence of cognitive impairment in LGMDR14 patients, a reliable application of functional outcome measures can be challenging, therefore a muscle MRI follow-up to assess disease evolution is recommended. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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37. Long View Of The Long Haul.
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Bruno, Claudio
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MARTIAN exploration - Abstract
A letter to the editor is presented in response to the article in the July 2, 2012 issue regarding the plans for the International Space Station and Mars missions, with particular focus on communications from the U.S. National Aeronautics and Space Administration (NASA) and other space agencies.
- Published
- 2012
38. CORRESPONDENCE.
- Author
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Bruno, Claudio, Evans, Stephen A., Glicksman, Jeffrey M., Castiel, Jose, and Wroble, Guy
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LETTERS to the editor , *MILITARY airplanes , *STEALTH aircraft , *MILITARY jets , *F-22 (Jet fighter plane) - Abstract
This article presents letters to the editor in response to articles or letters to the editor published in previous issues, including letters from Dale L. Jensen and Steven D. Green, both in the April 19, 2010 issue, and an article entitled "Enhancing Stealth," in the April 26, 2010 issue.
- Published
- 2010
39. CORRESPONDENCE.
- Author
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Bruno, Claudio, Reed, Allan H., Speth, Joe, Birken, David, Traceski, Frank T., and Asplundh, Edward K.
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LETTERS to the editor , *AEROSPACE industries , *AERONAUTICS , *COMMERCIAL aeronautics - Abstract
Several letters to the editor are presented in response to articles in previous issues including the decreasing interest in science, technology, engineering and math (STEM) education and careers in the June 15, 2009 issue, the critical aerospace capabilities of the U.S. in the July 13, 2009 issue and "Nearing Burnout" in the June 29, 2009 issue.
- Published
- 2009
40. 2-Year Change in Revised Hammersmith Scale Scores in a Large Cohort of Untreated Paediatric Type 2 and 3 SMA Participants.
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Stimpson, Georgia, Ramsey, Danielle, Wolfe, Amy, Mayhew, Anna, Scoto, Mariacristina, Baranello, Giovanni, Muni Lofra, Robert, Main, Marion, Milev, Evelin, Coratti, Giorgia, Pane, Marika, Sansone, Valeria, D'Amico, Adele, Bertini, Enrico, Messina, Sonia, Bruno, Claudio, Albamonte, Emilio, Mazzone, Elena Stacy, Montes, Jacqueline, and Glanzman, Allan M.
- Subjects
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SPINAL muscular atrophy , *PEDIATRICS , *AGE groups - Abstract
The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale–Expanded (HFMSE). These change scores were considered by SMA type, motor function, and baseline RHS score. We consider a new transitional group, spanning crawlers, standers, and walkers-with-assistance, and analyse that alongside non-sitters, sitters, and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. In the weakest patients, we are most able to detect positive change in the RHS in the under-5 age group, whereas in the stronger patients, we are most able to detect decline in the RHS in the 8–13 age group. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
41. Using Cluster Analysis to Overcome the Limits of Traditional Phenotype–Genotype Correlations: The Example of RYR1 -Related Myopathies.
- Author
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Dosi, Claudia, Rubegni, Anna, Baldacci, Jacopo, Galatolo, Daniele, Doccini, Stefano, Astrea, Guja, Berardinelli, Angela, Bruno, Claudio, Bruno, Giorgia, Comi, Giacomo Pietro, Donati, Maria Alice, Dotti, Maria Teresa, Filosto, Massimiliano, Fiorillo, Chiara, Giannini, Fabio, Gigli, Gian Luigi, Grandis, Marina, Lopergolo, Diego, Magri, Francesca, and Maioli, Maria Antonietta
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CLUSTER analysis (Statistics) , *K-means clustering , *MULTIDIMENSIONAL scaling , *MUSCLE diseases , *NUCLEOTIDE sequencing , *PHENOTYPES - Abstract
Thanks to advances in gene sequencing, RYR1-related myopathy (RYR1-RM) is now known to manifest itself in vastly heterogeneous forms, whose clinical interpretation is, therefore, highly challenging. We set out to develop a novel unsupervised cluster analysis method in a large patient population. The objective was to analyze the main RYR1-related characteristics to identify distinctive features of RYR1-RM and, thus, offer more precise genotype–phenotype correlations in a group of potentially life-threatening disorders. We studied 600 patients presenting with a suspicion of inherited myopathy, who were investigated using next-generation sequencing. Among them, 73 index cases harbored variants in RYR1. In an attempt to group genetic variants and fully exploit information derived from genetic, morphological, and clinical datasets, we performed unsupervised cluster analysis in 64 probands carrying monoallelic variants. Most of the 73 patients with positive molecular diagnoses were clinically asymptomatic or pauci-symptomatic. Multimodal integration of clinical and histological data, performed using a non-metric multi-dimensional scaling analysis with k-means clustering, grouped the 64 patients into 4 clusters with distinctive patterns of clinical and morphological findings. In addressing the need for more specific genotype–phenotype correlations, we found clustering to overcome the limits of the "single-dimension" paradigm traditionally used to describe genotype–phenotype relationships. [ABSTRACT FROM AUTHOR]
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- 2023
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42. Long term follow-up of scoliosis progression in type II SMA patients.
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Coratti, Giorgia, Pera, Maria Carmela, D'Amico, Adele, Bruno, Claudio, Bovis, Francesca, Gullì, Consolato, Brolatti, Noemi, Pedemonte, Marina, Apicella, Massimo, Antonaci, Laura, Ricci, Martina, Capasso, Anna, Cicala, Gianpaolo, Cutrona, Costanza, de Sanctis, Roberto, Carnicella, Sara, Forcina, Nicola, Catteruccia, Michela, Damasio, Maria Beatrice, and Labianca, Luca
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SCOLIOSIS , *SITTING position , *SPINAL muscular atrophy - Abstract
• The aim was to evaluate scoliosis onset and progression in untreated type II SMA patients. • The mean annual rate of increase of scoliosis angle was 5.63 (95%CI: 4.74–6.52). • The progression of scoliois angles was related to different variables. • Angles progressively increased with decreasing HFMSE scores or increasing age. • Our results confirm the progression of scoliosis in type II SMA. The aim of this study is to retrospectively assess onset and progression of scoliosis in type II SMA patients not treated with the approved disease modifying treatments. Scoliosis was evaluated by measuring the scoliosis angle on X-ray obtained in the anteroposterior view in sitting position (Cobb's angle method). Eighty-four patients had at least one assessment of scoliosis angle (287 assessments). There was a positive correlation between age and scoliosis angles (p <0.001) with a progressive increase of scoliosis with age. When subdividing the population by HFMSE score (<10; 11–22;> 22), there was a progressive increase in scoliosis angles with decreasing HFMSE scores. The difference between HFMSE categories was significant (p <0.001). Fifty-four patients had at least two assessments at 6-month distance and were retained for the longitudinal analysis. Using a mixed model, age, functional status and scoliosis angle at baseline were predictive on scoliosis progression. The mean annual rate of increase of scoliosis angle was 5.63 (95%CI: 4.74–6.52). Our results confirm the progression of scoliosis in untreated type II SMA providing details of the progression in relation to different variables. With different therapeutical options being available in many countries, our findings will provide reference data for establishing possible differences in the trajectories of progression with treated type II individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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43. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial.
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Masson, Riccardo, Mazurkiewicz-Bełdzińska, Maria, Rose, Kristy, Servais, Laurent, Xiong, Hui, Zanoteli, Edmar, Baranello, Giovanni, Bruno, Claudio, Day, John W, Deconinck, Nicolas, Klein, Andrea, Mercuri, Eugenio, Vlodavets, Dmitry, Wang, Yi, Dodman, Angela, El-Khairi, Muna, Gorni, Ksenija, Jaber, Birgit, Kletzl, Heidemarie, and Gaki, Eleni
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SPINAL muscular atrophy , *RESPIRATORY infections , *SECONDARY analysis , *TODDLERS development , *NATURAL history - Abstract
Background: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment.Methods: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing.Findings: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p<0·0001 compared with the performance criterion derived from the natural history of untreated infants with type 1 spinal muscular atrophy). No infants could stand alone (0 [90% CI 0-7]) or walk alone (0 [0-7]) after 24 months of treatment. The most frequently reported adverse event was upper respiratory tract infection, in 22 infants (54%); the most common serious adverse events were pneumonia in 16 infants (39%) and respiratory distress in three infants (7%).Interpretation: Treatment with risdiplam over 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The FIREFISH open-label extension phase will provide additional evidence regarding long-term safety and efficacy of risdiplam.Funding: F Hoffmann-La Roche. [ABSTRACT FROM AUTHOR]- Published
- 2022
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44. Corrigendum to “Unclassified polysaccharidosis of the heart and skeletal muscle in siblings” [Mol. Genet. Metabol. 95 (2008) 52–58]
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Schoser, Benedikt, Bruno, Claudio, Schneider, Hans-Christian, Shin, Yoon S., Podskarbi, Teodor, Goldfarb, Lev, Müller-Felber, Wolfgang, and Müller-Höcker, Josef
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- 2009
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45. Accuracy of Ultrasonography and Magnetic Resonance Imaging in the Diagnosis of Placenta Accreta.
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Jaraquemada, José Miguel Palacios and Bruno, Claudio Hernán
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LETTERS to the editor , *DIAGNOSIS of placenta diseases - Abstract
A letter to the editor is presented as a response to an article on the accuracy of magnetic resonance imaging and ultrasonography in the diagnosis of placenta accreta.
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- 2007
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46. Long term follow-up in two siblings with Sengers syndrome: Case report.
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Panicucci, Chiara, Schiaffino, Maria Cristina, Nesti, Claudia, Derchi, Maria, Trocchio, Gianluca, Severino, Mariasavina, Stagnaro, Nicola, Priolo, Enrico, Zara, Federico, Santorelli, Filippo M., and Bruno, Claudio
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PATIENT aftercare , *CATARACT , *GENETIC mutation , *MITOCHONDRIAL pathology , *CARDIOMYOPATHIES , *GENETIC disorders , *SYMPTOMS , *LONG-term health care , *PHENOTYPES - Abstract
Background: Sengers syndrome is characterized by congenital cataract, hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis associated with mutations in AGK gene. Clinical course ranges from a severe fatal neonatal form, to a more benign form allowing survival into adulthood, to an isolated form of congenital cataract. Thus far few reported cases have survived the second decade at their latest examination, and no natural history data are available for the disease. Case presentation: Here we provide a 20-year follow-up in two siblings with a benign form of Sengers syndrome, expanding the phenotypical spectrum of the disease by reporting a condition of ovarian agenesis. Conclusion: To our knowledge, this report provides the first longitudinal data of Sengers syndrome patients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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47. Nusinersen Induces Disease-Severity-Specific Neurometabolic Effects in Spinal Muscular Atrophy.
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Errico, Francesco, Marino, Carmen, Grimaldi, Manuela, Nuzzo, Tommaso, Bassareo, Valentina, Valsecchi, Valeria, Panicucci, Chiara, Di Schiavi, Elia, Mazza, Tommaso, Bruno, Claudio, D'Amico, Adele, Carta, Manolo, D'Ursi, Anna Maria, Bertini, Enrico, Pellizzoni, Livio, and Usiello, Alessandro
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SPINAL muscular atrophy , *AMINO acid metabolism , *CEREBROSPINAL fluid examination , *NUCLEAR magnetic resonance , *MOTOR neurons , *CEREBROSPINAL fluid , *GLUCOSE metabolism - Abstract
Intrathecal delivery of Nusinersen–an antisense oligonucleotide that promotes survival motor neuron (SMN) protein induction–is an approved therapy for spinal muscular atrophy (SMA). Here, we employed nuclear magnetic resonance (NMR) spectroscopy to longitudinally characterize the unknown metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of SMA patients across disease severity. Modulation of amino acid metabolism is a common denominator of biochemical changes induced by Nusinersen, with distinct downstream metabolic effects according to disease severity. In severe SMA1 patients, Nusinersen stimulates energy-related glucose metabolism. In intermediate SMA2 patients, Nusinersen effects are also related to energy homeostasis but involve ketone body and fatty acid biosynthesis. In milder SMA3 patients, Nusinersen mainly modulates amino acid metabolism. Moreover, Nusinersen modifies the CSF metabolome of a more severe clinical group towards the profile of untreated SMA patients with milder disease. These findings reveal disease severity-specific neurometabolic signatures of Nusinersen treatment, suggesting a selective modulation of peripheral organ metabolism by this CNS-directed therapy in severe SMA patients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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48. Genetic modifiers of upper limb function in Duchenne muscular dystrophy.
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Sabbatini, Daniele, Fusto, Aurora, Vianello, Sara, Villa, Matteo, Janik, Joanna, D'Angelo, Grazia, Diella, Eleonora, Magri, Francesca, Comi, Giacomo P., Panicucci, Chiara, Bruno, Claudio, D'Amico, Adele, Bertini, Enrico, Astrea, Guja, Battini, Roberta, Politano, Luisa, Masson, Riccardo, Baranello, Giovanni, Previtali, Stefano C., and Messina, Sonia
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DUCHENNE muscular dystrophy , *GENERALIZED estimating equations , *DELAYED onset of disease , *EXPERIMENTAL design , *GENETIC variation - Abstract
Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations. [ABSTRACT FROM AUTHOR]
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- 2022
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49. A Stop-Codon Mutation in the Human mtDNA Cytochrome c Oxidase I Gene Disrupts the Functional Structure of Complex IV.
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Bruno, Claudio, Martinuzzi, Andrea, Yingying Tang, Andreu, Antoni L., Palloti, Francesco, Bonilla, Eduardo, Shaske, Sara, Jin Fu, Sue, Carolyn M., Angelini, Corrado, DiMauro, Salvatore, and Manfredi, Giovanni
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GENETIC mutation , *MITOCHONDRIAL pathology - Abstract
Examines the mutation of mtDNA with multisystem mitochondrial disorder. Histochemical analysis on the muscle biopsy; Absence of cythochome oxidase; Disruptions in the assembly of respiratory-chain complex IV.
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- 1999
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50. Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study.
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Cances, Claude, Vlodavets, Dmitry, Comi, Giacomo Pietro, Masson, Riccardo, Mazurkiewicz-Bełdzińska, Maria, Saito, Kayoko, Zanoteli, Edmar, Dodman, Angela, El-Khairi, Muna, Gorni, Ksenija, Gravestock, Isaac, Hoffart, Janine, Scalco, Renata S., Darras, Basil T., the ANCHOVY Working Group, Alberti, Katia, Baranello, Giovanni, Barisic, Nina, Brolatti, Noemi, and Bruno, Claudio
- Abstract
Background: ANCHOVY was a global, multicenter, chart-review study that aimed to describe the natural history of Type 1 spinal muscular atrophy (SMA) from a broad geographical area and provide further contextualization of results from the FIREFISH (NCT02913482) interventional study of risdiplam treatment in Type 1 SMA.Methods: Data were extracted from medical records of patients with first symptoms attributable to Type 1 SMA between 28 days and 3 months of age, genetic confirmation of SMA, and confirmed survival of motor neuron 2 copy number of two or unknown. The study period started on 1 January 2008 for all sites; study end dates were site-specific due to local treatment availabilities. Primary endpoints were time to death and/or permanent ventilation and proportion of patients achieving motor milestones. Secondary endpoints included time to initiation of respiratory and feeding support.Results: Data for 60 patients from nine countries across Asia, Europe and North and South America were analyzed. The median age (interquartile range [IQR]) for reaching death or permanent ventilation was ~ 7.3 (5.9-10.5) months. The median age (IQR) at permanent ventilation was ~ 12.7 (6.9-16.4) months and at death was ~ 41.2 (7.3-not applicable) months. No patients were able to sit without support or achieved any level of crawling, standing or walking.Interpretation: Findings from ANCHOVY were consistent with published natural history data on Type 1 SMA demonstrating the disease's devastating course, which markedly differed from risdiplam-treated infants (FIREFISH Part 2). The results provide meaningful additions to the literature, including a broader geographical representation. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
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