Photocrystallography

Photocrystallography is a relatively new and continuously developing technique used in the structure determination of metastable and transient species in the crystalline state. This thesis contains a description of investigations into photo-induced linkage isomerism reactions in the solid state with the use of single crystal and powder X-ray diffraction experiments to monitor structural changes at low temperature.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Identification of an intragenic deletion in the SGCB gene through a re-evaluation of negative next generation sequencing results

A large mutation screening of 504 patients with muscular dystrophy or myopathy has been performed by next generation sequencing (NGS). Among this cohort of patients, we report a case with a severe form of muscular dystrophy with a proximal weakness in the limb-girdle muscles. Her biopsy revealed typical dystrophic features and immunohistochemistry for α- and γ-sarcoglycans showed an absent reaction, addressing the clinical diagnosis toward a sarcoglycanopathy. Considering that no causative point mutation was detected in any of the four sarcoglycan genes, we re-evaluated the NGS data by careful quantitative analysis of the specific reads mapping on the four sarcoglycan genes. A complete absence of reads from the sixth exon of the β-sarcoglycan gene was found. Subsequent array comparative genomic hybridization (CGH) analysis confirmed the result with the identification of a novel 3.3 kb intragenic deletion in the SGCB gene. This case illustrates the importance of a multidisciplinary approach involving clinicians and molecular geneticists and the need for a careful re-evaluation of NGS data

The role of echocardiography in SARS-CoV-2 pandemic: a compromise among appropriateness, safety and clinical impact

SARS-CoV-2 infection, responsible for COVID-19, can determine cardiac events, which require a quick diagnosis and management, and should not be overlooked due to the presence of COVID-19 infection. In some cases, cardiovascular symptoms can also be the first and only manifestation of SARS-CoV-2 infection. In patients with COVID-19, the full cardiovascular disease diagnostic algorithm can be hindered by logistic restrain mainly derived from the difficulty of transporting patients in critical conditions to Radiology or Hemodynamics wards. The echocardiography in SARS-CoV-2 pandemic can help for differential diagnosis of cardiac events, which can be related or unrelated by the infection and can likely impact on short-term prognosis. Indeed, transthoracic echocardiography plays a key role in the screen for CV complications of COVID-19 infection: it must be focused cardiac ultrasound study (FoCUS) performed at bedside. All transthoracic, transesophageal and stress echocardiograms in patients in which test results are unlikely to change the management strategy should be postponed

The position of nonsense mutations can predict the phenotype severity : A survey on the DMD gene

A nonsense mutation adds a premature stop signal that hinders any further translation of a protein-coding gene, usually resulting in a null allele. To investigate the possible exceptions, we used theDMDgene as an ideal model. First, because dystrophin absence causes Duchenne muscular dystrophy (DMD), while its reduction causes Becker muscular dystrophy (BMD). Second, theDMDgene is X-linked and there is no second allele that can interfere in males. Third, databases are accumulating reports on many mutations and phenotypic data. Finally, becauseDMDmutations may have important therapeutic implications. For our study, we analyzed large databases (LOVD, HGMD and ClinVar) and literature and revised critically all data, together with data from our internal patients. We totally collected 2593 patients. Positioning these mutations along the dystrophin transcript, we observed a nonrandom distribution of BMD-associated mutations within selected exons and concluded that the position can be predictive of the phenotype. Nonsense mutations always cause DMD when occurring at any point in fifty-one exons. In the remaining exons, we found milder BMD cases due to early 5' nonsense mutations, if reinitiation can occur, or due to late 3' nonsense when the shortened product retains functionality. In the central part of the gene, all mutations in some in-frame exons, such as in exons 25, 31, 37 and 38 cause BMD, while mutations in exons 30, 32, 34 and 36 cause DMD. This may have important implication in predicting the natural history and the efficacy of therapeutic use of drug-stimulated translational readthrough of premature termination codons, also considering the action of internal natural rescuers. More in general, our survey confirm that a nonsense mutation should be not necessarily classified as a null allele and this should be considered in genetic counselling.Peer reviewe

Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease

Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle diseasegenes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T > G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

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

Il Laboratorio sulla corporeità per la disabilità dell’Università di Salerno: un breve report.

Vengono descritti gli aspetti organizzativi e metodologici del laboratorio sulla corporeità, nonché alcuni esit

The workshop on the corporeality of the University of Salerno. A study on the evaluation of corporal self-esteem of students with disabilities

Oftentimes, in motor disability, the bodily experience can generate anxiety, due to living the difference of one’s body compared to that of non-disabled people and, possible difficulties in the independent management of one’s bodily functions (Parente, 2005; Festa and Drigho, 2013). This can have an impact on one’s self-confidence. On the basis of these considerations, during the academic year 2014-15, the University of Salerno promoted and launched a project called “Workshop on corporeality”, directed to all students, with the intention of: - Promoting the development of possible body languages, starting from the experience one’s body; - Analyzing through stimuli and symbolic languages the bodily experience of each participant; - Building or rebuilding, by working in groups, the body esteem of each participant; - Strengthening the possibilities of meeting and relationship between the participants through physical contact and the sharing of a common project. At the beginning of this path, we administered to 22 participants (with and without motor disabilities; mean age 19.11; all females) the TMA questionnaire (Multidimensional Assessment Test by Bracken, 1993), in particular the scale of bodily experience. The aim was to assess: 1) if university students with physical disabilities had negative self-esteem, especially in the bodily expeience; compare these data with those of a group of female university students with typical development (comparative group); 2) whether university students, disabled and not disabled, with a negative bodily experience chose to attend a workshop on corporeality. The results show how the body esteem of both students with disabilities and non-disabled participants in the workshop is “slightly negative” or “very negative”. Self-esteem for the comparison group was found to be “average”