Health Surveillance and Response to SARS-CoV-2 Mass Testing in Health Workers of a Large Italian Hospital in Verona, Veneto

Italy presented the first largest COVID-19 outbreak outside of China. Veneto currently ranks fourth among the Italian regions for COVID-19 confirmed cases (~19,000). This study presents health surveillance data for SARS-CoV-2 in 6100 health workers (HW) employed in a large public hospital. Workers underwent oropharyngeal and nasopharyngeal swabs, with a total of 5942 participants (97.5% of the population). A total of 11,890 specimens were tested for SARS-CoV-2 infection using PCR, identifying the viral genes E, RdRP, and N. Positive tests were returned for 238 workers (cumulative incidence of 4.0%, similar in both COVID and nonCOVID units). SARS-CoV-2 risk was not affected by gender, age, or job type, whereas work setting and occupation were both predictors of infection. The risk was higher in medical wards (OR 2.7, 95% CI 1.9\u20133.9) and health services (OR 4.3, 95% CI 2.4\u20137.6), and lower in surgical wards and administration areas. To our knowledge, this study represents the largest available HW case list swab-tested for SARS-CoV-2, covering almost the total workforce. Mass screening enabled the isolation of HW, improved risk assessment, allowed for close contacts of and infected HW to return to work, provided evidence of SARS-CoV-2 diffusion, and presented solid ground to prevent nosocomial SARS-CoV-2 infections. The ongoing concurrent sero-epidemiological study aims to enable the improvement of health surveillance to maintain the safety of HWs and the communities they serve

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

An important target in the understanding of the pathogenesis of acute myeloid leukemias (AML) relies on deciphering the molecular features of normal and leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms involved in the regulation of cell proliferation is decisive for the establishment of new targeted therapies. To gain further insight into this topic we report herein a novel approach by analyzing the role of HERG K+ channels in the regulation of hemopoietic cell proliferation. These channels, encoded by the human ether-a-go-go-related gene (herg), belong to a family of K, channels, whose role in oncogenesis has been recently demonstrated. We report here that herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34(+) cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, herg appears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. Evidence is also provided that HERG channel activity regulates cell proliferation in stimulated CD34(+) as well as in blast cells from AML patients. These results open new perspectives on the pathogenetic role of HERG K+ channels in leukemias

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

Polyglutamine-Expanded Androgen Receptor Alteration of Skeletal Muscle Homeostasis and Myonuclear Aggregation Are Affected by Sex, Age and Muscle Metabolism

Polyglutamine (polyQ) expansions in the androgen receptor (AR) gene cause spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease characterized by lower motor neuron (MN) loss and skeletal muscle atrophy, with an unknown mechanism. We generated new mouse models of SBMA for constitutive and inducible expression of mutant AR and performed biochemical, histological and functional analyses of phenotype. We show that polyQ-expanded AR causes motor dysfunction, premature death, IIb-to-IIa/IIx fiber-type change, glycolytic-to-oxidative fiber-type switching, upregulation of atrogenes and autophagy genes and mitochondrial dysfunction in skeletal muscle, together with signs of muscle denervation at late stage of disease. PolyQ expansions in the AR resulted in nuclear enrichment. Within the nucleus, mutant AR formed 2% sodium dodecyl sulfate (SDS)-resistant aggregates and inclusion bodies in myofibers, but not spinal cord and brainstem, in a process exacerbated by age and sex. Finally, we found that two-week induction of expression of polyQ-expanded AR in adult mice was sufficient to cause premature death, body weight loss and muscle atrophy, but not aggregation, metabolic alterations, motor coordination and fiber-type switch, indicating that expression of the disease protein in the adulthood is sufficient to recapitulate several, but not all SBMA manifestations in mice. These results imply that chronic expression of polyQ-expanded AR, i.e. during development and prepuberty, is key to induce the full SBMA muscle pathology observed in patients. Our data support a model whereby chronic expression of polyQ-expanded AR triggers muscle atrophy through toxic (neomorphic) gain of function mechanisms distinct from normal (hypermorphic) gain of function mechanisms

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Life and death in audience development. The exhibition on Pompeii at the British museum, 2013

Values and orientations of cultural professionals are important to understand the performance of the institutions they manage. While there are striking differences in orientation across countries, their impact has rarely been investigated systematically. This paper offers a case study of a blockbuster exhibition mounted by the British Museum in 2013 using objects loaned by the Superintendence of Napoli and Pompeii. Based on interviews and documentary sources, the study analyzes and explains the perceptions of the Italian professionals with relation to the value and the payoffs of the exhibition, and critically compares these to those of the British Museum. The Italian authority did not recognise the strategic potential of the partnership with the British Museum. Consequently it did not pursue or win any significant gains in the areas of resources, reputation or audience development

La percezione della presenza e la proiezione dell'identità nei sistemi blended

Indagine sulla percezione della presenza mediata dalle nuove tecnologie e contestualizzata all'interno di una precisa esperienza di apprendimento, il Master "Progettista e gestore di formazione in rete" erogato dall'Universita' di Firenze

Problematiche diagnostiche nelle infezioni sostenute da Legionella pneumophila

The introduction of the research of Legionella antigen in urine has significantly speeded up the diagnosis of Legionella pneumophila infections but has decreased the number of respiratory samples submitted for coltural examination. In 2001 respiratory samples were submitted to our laboratory only from 7% of patients for which antigen detection in urine was requested. Such a percentage decreased to 4% in 2002 and to 2.5% in 2003. For 2 of 14 patients tested in 2002, legionellosis diagnosis could not be confirmed since urine antigen detection provided weak positive values and either respiratory samples for direct isolation of L. pneumophila or blood samples for specific serology tests were lacking.We believe that even if urine antigen detection test is a very useful quick test, it cannot be considered as the only diagnostic tool in Legionella spp. infections