Italia-Germania, una comparazione dei livelli di competitivit\ue0 industriale

L\u2019indagine \ue8 stata realizzata dagli uffici dell\u2019area Lavoro e previdenza di Confindustria Bergamo e da ADAPT/Universit\ue0 degli Studi di Modena e Reggio Emilia, con il supporto scientifico ed operativo rispettivamente del Prof. Maurizio Del Conte dell\u2019Universit\ue0 Bocconi di Milano e del Prof. Michele Tiraboschi dell\u2019Universit\ue0 degli Studi di Modena e Reggio Emilia. La parte I, di carattere riassuntivo, esprime la valutazione di Confindustria Bergamo sugli esiti complessivi dell\u2019analisi normativa e della campionatura di esperienze aziendali realizzata. Le due note di approfondimento allegate sono state invece realizzate dai referenti scientifici Maurizio Del Conte e Michele Tiraboschi e riportano le opinioni degli AA. La parte II \ue8 stata redatta da Benedetto Fratello, avvocato giuslavorista e dottore di ricerca in diritto del lavoro presso l\u2019Universit\ue0 Bocconi di Milano (primo capitolo) e da Simone Caroli, Emmanuele Massagli, Davide Mosca e Paolo Tomassetti, ricercatori ADAPT (secondo capitolo). La parte III \ue8 stata redatta da Marina Mariani di Confindustria Bergamo, dottore di ricerca in formazione della persona e mercato del lavoro presso l\u2019Universit\ue0 degli Studi di Bergamo

Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy

Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the alpha II-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative alpha II-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes

Which laboratory technique is used for the blood sodium analysis in clinical research? A systematic review

Abstract Background Circulating sodium is analyzed by flame spectrometry and indirect or direct potentiometry. The differences between estimates returned by the three techniques are often relevant. It is unknown whether peer-reviewed international publications focusing on this parameter provide information about the technique. Objectives of the study were to ascertain if information about the employed technique is provided. Content A search in the National Library of Medicine for articles whose title contains "hyponatr[a]emia" was performed. We restricted the search to clinical reports including 10 or more humans published in the 2013–2015 and 2017–2019 periods. Authors of papers not reporting the technique were contacted to obtain this information. The study design and journal quartile ranking of each article were also evaluated. Summary For the final analysis, we included 361 articles (2013–2015, n=169; 2017–2019, n=192). Information about the laboratory technique was given in 61(17%) articles. Thanks to our inquiry, we collected this information for 116(32%) further reports. Indirect potentiometry was the most frequently used technique, followed by direct potentiometry. Spectrometry was used in a small minority of studies. Study design, journal ranking and study period did not modulate the mentioned frequency. Outlook Most articles focusing on hyponatremia do not provide information on the laboratory technique. This parameter is nowadays analyzed by indirect or, less frequently, direct potentiometry. The figures are similar for high and low impact factor journals and for the 2013–2015 and the 2017–2019 periods. Many authors, reviewers and editors likely assume that the results of this parameter are not influenced by the technique

CONGENITAL MYOPATHIES

n/

Next-generation sequencing approach to hyperCKemia: A 2-year cohort study

ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance

CONGENITAL MYOPATHIES

n/

Bilateral linear scleroderma "en coup de sabre" associated with facial atrophy and neurological complications

BACKGROUND: Linear scleroderma "en coup de sabre" (LSCS) usually affects one side of the face and head in the frontoparietal area with band-like indurated skin lesions. The disease may be associated with facial hemiatrophy. Various ophthalmological and neurological abnormalities have been observed in patients with LSCS. We describe an unusual case of LSC. CASE PRESENTATION: A 23 year old woman presented bilateral LSCS and facial atrophy. The patient had epileptic seizures as well as oculomotor and facial nerve palsy on the left side which also had pronounced skin involvement. Clinical features of different stages of the disease are presented. CONCLUSIONS: The findings of the presented patient with bilateral LSCS and facial atrophy provide further evidence for a neurological etiology of the disease and may also indicate that classic progressive facial hemiatrophy (Parry-Romberg syndrome) and LSCS actually represent different spectra of the same disease

Next-generation sequencing approach to hyperCKemia: A 2-year cohort study

Next-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition

Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study

Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity-there are over 80 potential disease-associated genes-and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel (SpastiSure3.0) comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several in silico tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy

Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis