Les hommes de science napolitains en exil en France, des passeurs scientifiques et politiques (1799-1820)

L’article analyse, en se concentrant sur l’exemple napolitain, comment l’exil politique a pu favoriser l’innovation scientifique et technique dans le royaume de Naples par la confrontation avec le contexte culturel et scientifique francais, et par l’insertion des savants en exil dans les reseaux et dans les structures de formation transalpines. Il illustre egalement, a partir de l’experience de l’exil, les modalites par lesquelles les exiles ont cherche a s’inspirer, a leur retour, des instances francaises de l’innovation scientifique et technique. Il evalue enfin les effets de ces processus de mediation sur le royaume de Naples, en mettant en evidence les reactions de la societe napolitaine face a ces influences culturelles exterieures.The paper proposes a reflection, focusing on the Neapolitan case, on how political exile was able to promote scientific and technical innovation in the Southern Kingdom thanks to a comparison with the French cultural and scientific context and the integration of exiled scientists in Transalpine networks and educational facilities. Focusing on exile as a life experience, the paper also examines the ways in which former exiles drew inspiration from French scientific and technical innovation upon their return. Finally, it evaluates the impact of these mediation processes on the Southern Kingdom, highlighting Naples’ reaction towards the circulation of foreign cultural influcnces.Der Artikel analysiert am Beispiel Neapels, wie politisches Exil durch den Kontakt mit den franzosischen Kultur- und Wissenschaftstraditionen sowie die Einbindung der exilierten Gelehrten in Netzwerke und Bildungsstrukturen jenseits der Alpen wissenschaftliche und technische Neuerungen im Konigreich Neapel beforderte. Ausgehend von der Erfahrung des Exils zeigt der Artikel sodann, wie sich die exilierten Gelehrten nach ihrer Ruckkehr in Bezug auf wissenschaftliche und technische Innovationen am franzosischen Vorbild zu orientieren suchten. Abschliesend wird die Bedeutung des Wissenstransfers durch die Exilanten im neapolitanischen Konigreich bewertet, indem die Reaktionen der neapolitanischen Gesellschaft auf die kulturellen Einflusse von ausen in den Blick genommen werden

Surgical treatment of an aseptic fistulized acromioclavicular joint cyst: a case report and review of the literature

An acromioclavicular joint cyst is an uncommonly reported condition, which seems to result from a massive rotator cuff tear and degenerative osteoarthritis of the acromioclavicular joint. We present the case of an 81-year-old man affected by an acromioclavicular joint cyst, associated to a massive rotator cuff tear, proximal migration of the humeral head and osteoarthritis of the gleno-humeral joint. The mass was 7 × 2.5 cm in size and the overlying skin presented a fistula that drained clear synovial-like fluid. Plain X-ray examination of the left shoulder showed proximal migration of the humeral head migration and osteoarthritis of the gleno-humeral joint, and further MRI evaluation confirmed the clinical diagnosis of a complete rotator cuff tear and observed a large subcutaneous cyst in communication with the degenerative acromioclavicular joint. The patient underwent surgical excision of the cyst and lateral resection of the clavicle to prevent disease recurrence. To the best of our knowledge, this is the first reported case of an acromioclavicular joint cyst complicated by an aseptic fistula resulting from multiple aspirations

Post-vaccine measles in a child with concomitant influenza, Sicily, Italy, March 2015

We describe the occurrence of measles in an 18 monthold patient in Sicily, Italy, in March 2015, who received the first dose of a measles-containing vaccine seven days before onset of prodromal symptoms. Measles virus infection was confirmed by PCR and detection of specific immunoglobulin; viral genotyping permitted the confirmation of a vaccine-associated illness. The patient had a concurrent influenza virus infection, during a seasonal epidemic outbreak of influenza

Immediate early genes regulation in rat cerebellar cortex during long-term synaptic plasticity induction

The cerebellum is one of the brain areas involved in learning and memory formation. Long-term synaptic plasticity is thought to play a pivotal role in supporting these functions. Moreover Immediate Early Genes (IEGs) expression and de novo protein synthesis and/or modification have been strictly associated with maintenance of Long-Term Potentiation (LTP) as well as memory consolidation and storage. Two highly conserved signalling cascades, PKA and MAPK, seem to be involved in early- to late-LTP conversion; both pathway can activate CREB transcription factor through phosphorylation and P-CREB has been suggested to initiate the protein synthesis leading to late-LTP induction. The transcription factor c-fos is known to be rapidly and transiently induced in the Nervous System by a variety of stimuli and is thought to be directly involved in processes of neuronal plasticity including LTP. We used rat parasagittal cerebellar slices as a model system in which specific patterns of stimulation delivered to the mossy fibers can induce both Long-Term Potentiation and Long-Term Depression (LTD), depending on local inhibition and other regulating factors. Using Voltage Sensitive Dye (VSD) imaging we obtained high-resolution maps of the spatial distribution of LTP/LTD induced from a Teta Burst Stimulus (TBS) application. Control and stimulated slices were fixed at different times from the TBS application and processed for in situ hybridization or immunohystochemistry in order to detect IEGs mRNA expression patterns and protein expression/modifications. The expression pattern of c-fos and CREB mRNAs and their protein distribution and/or phosphorylation were then correlated with LTP/LTD maps generated by VSD imaging. Preliminary data indicate a significant increase of P-CREB in the granular layer suggesting that CREB phosphorylation is induced as early as 15 minutes post TBS application. In situ hybridization experiments indicate a good correlation between c-fos and CREB mRNAs up-regulation and LTP distribution at 120 minutes post TBS. At the protein level, the comparison of immunofluorescence signals and VSD immaging data indicate a clear correlation between c-Fos and P-CREB distribution and synaptic plasticity patterns. We are planning further experiments to confirm these data and to test our experimental system in the presence of drugs that could interfere with the transcription, translation or post-translational protein regulation

Immediate early genes expression in the cerebellar cortex correlates with LTP and LTD induction

The consolidation of changes following activity-dependent neural plasticity are believed to involve specific patterns of gene expression. In the hippocampus, immediate early genes are thought to contribute to long-term synaptic plasticity (LTP and LTD); this phenomenon may occur also in the cerebellum, in which the transcription factors c-Fos and P-CREB have been identified. The cerebellum granular layer (GL) can manifest both LTP and LTD following a Theta Burst Stimulus (TBS) delivered to the mossy fibers. We have employed VSD imaging in rat cerebellar slices (P18-24) in order to map the spatial distribution of LTP and LTD in the cerebellum GL. Fluorescence changes were correlated to LTP or LTD in two different post-TBS time ranges (15 and 120 min). Slices were then fixed and processed for immunohistochemistry in order to identify levels of c-Fos and P-CREB expression. The induction of long-term plasticity increased the average level of P-CREB both at 15 min (+39±4.9, p<0.01%) and 120 min (+24±7.2, p<0.05%) after TBS. The level of c-Fos was unaltered at 15 min, while it significantly increased at 120 min (+37±8.9, p<0.05%). By spatially correlating longterm synaptic plasticity with the corresponding variation of P-CREB and c-Fos, we observed that regions showing LTP well correlated (p<0.05) with positive variations of P-CREB and c-Fos. Conversely, areas showing LTD correlated exclusively (p<0.05) with negative variations of P-CREB. Slices were also evaluated by in situ hybridization and a similar analysis was performed. The levels of fos and CREB mRNA expression and their spatial correlation with the sign of long-term synaptic plasticity corresponded with the immunohistochemical results. As a further test, VSD recordings showed that the induction of granular layer LTP and LTD could be prevented by applying 50 mM D-APV, a selective NMDA receptor blocker. Moreover, in situ hybridization and immunohistochemistry analysis evidenced that in these conditions both mRNA and protein expression levels of c-fos and CREB were unchanged, confirming the involvement of these two transcription factors in cerebellar granular layer plasticity

Co-occurrence of Beckwith-Wiedemann syndrome and pseudohypoparathyroidism type 1B: coincidence or common molecular mechanism?

Imprinting disorders are congenital diseases caused by dysregulation of genomic imprinting, affecting growth, neurocognitive development, metabolism and cancer predisposition. Overlapping clinical features are often observed among this group of diseases. In rare cases, two fully expressed imprinting disorders may coexist in the same patient. A dozen cases of this type have been reported so far. Most of them are represented by individuals affected by Beckwith–Wiedemann spectrum (BWSp) and Transient Neonatal Diabetes Mellitus (TNDM) or BWSp and Pseudo-hypoparathyroidism type 1B (PHP1B). All these patients displayed Multilocus imprinting disturbances (MLID). Here, we report the first case of co-occurrence of BWS and PHP1B in the same individual in absence of MLID. Genome-wide methylation and SNP-array analyses demonstrated loss of methylation of the KCNQ1OT1:TSS-DMR on chromosome 11p15.5 as molecular cause of BWSp, and upd(20)pat as cause of PHP1B. The absence of MLID and the heterodisomy of chromosome 20 suggests that BWSp and PHP1B arose through distinct and independent mechanism in our patient. However, we cannot exclude that the rare combination of the epigenetic defect on chromosome 11 and the UPD on chromosome 20 may originate from a common so far undetermined predisposing molecular lesion. A better comprehension of the molecular mechanisms underlying the co-occurrence of two imprinting disorders will improve genetic counselling and estimate of familial recurrence risk of these rare cases. Furthermore, our study also supports the importance of multilocus molecular testing for revealing MLID as well as complex cases of imprinting disorders

Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature.Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas.Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches.Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections