111 research outputs found

    DNA Sensors’ Signaling in NK Cells During HHV-6A, HHV-6B and HHV-7 Infection

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    Objectives: The host DNA sensor proteins TLR9, STING, IFI16 are central signaling molecules that control the innate immune response to cytosolic nucleic acids. Here we propose to investigate how Natural killer (NK) cell infection by human herpesvirus (HHV)-6A, HHV-6B or HHV-7 is able to modify DNA sensor signaling in NK cells. Methods: We infected the NK92 cell line and primary NK cells with cell-free inocula of HHV-6A, HHV-6B or HHV-7 and evaluated TLR9, STING, and IFI16 pathway expression by Real-Time PCR, Western Blot, immunofluorescence and flow cytometry for 1, 2, 3, and 6 days post-infection. We evaluated NK cell cytokine-producing by Real-Time PCR and enzyme immunosorbent assay. Results: NK92 and primary NK cells were promptly infected by three viruses, as demonstrated by virus presence (DNA) and transcription (RNA) analysis. Our data show STING/STAT6 up-modulation in HHV-6A infected NK cells. NK cells infected with HHV-6B and HHV-7 up-regulated CCL3, IFN-alpha, TNF-alpha, IL-8 and IFN-gamma and slightly induced IL-4, and CCL4. HHV-6A infected NK cells up-regulated IL-4 and IL-13 and slightly induced IL-10, TNF-alpha, IFN-alpha, and IFN-gamma. Conclusion: For the first time, we demonstrate that HHV-6A, HHV-6B, and HHV-7 infections have a differential impact on intracellular DNA sensors. HHV-6B and HHV-7 mainly lead to the active control of in vivo viral spreading by pro-inflammatory cytokine secretion via TLR9. HHV-6A infected NK cells conversely induced STING/STAT6 pathway, as a mechanism of anti-viral activation, but they were characterized by a Th2 type response and a non-cytotoxic profile, suggesting a potential novel mechanism of HHV-6A-mediated immunosuppression

    Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study

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    Purpose: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. Methods: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January\u2013February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. Results: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). Conclusions: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management

    Main clinical features in patients at their first psychiatric admission to Italian acute hospital psychiatric wards. The PERSEO study

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    BACKGROUND: Few data are available on subjects presenting to acute wards for the first time with psychotic symptoms. The aims of this paper are (i) to describe the epidemiological and clinical characteristics of patients at their first psychiatric admission (FPA), including socio-demographic features, risk factors, life habits, modalities of onset, psychiatric diagnoses and treatments before admission; (ii) to assess the aggressive behavior and the clinical management of FPA patients in Italian acute hospital psychiatric wards, called SPDCs (Servizio Psichiatrico Diagnosi e Cura = psychiatric service for diagnosis and management). METHOD: Cross-sectional observational multi-center study involving 62 Italian SPDCs (PERSEO – Psychiatric EmeRgency Study and EpidemiOlogy). RESULTS: 253 FPA aged <= 40 were identified among 2521 patients admitted to Italian SPDCs over the 5-month study period. About half of FPA patients showed an aggressive behavior as defined by a Modified Overt Aggression Scale (MOAS) score greater than 0 Vs 46% of non-FPA patients (p = 0.3651). The most common was verbal aggression, while about 20% of FPA patients actually engaged in physical aggression against other people. 74% of FPA patients had no diagnosis at admission, while 40% had received a previous psychopharmacological treatment, mainly benzodiazepines and antidepressants. During SPDC stay, diagnosis was established in 96% of FPA patients and a pharmacological therapy was prescribed to 95% of them, mainly benzodiazepines, antipsychotics and mood stabilizers. CONCLUSION: Subjects presenting at their first psychiatric ward admission have often not undergone previous adequate psychiatric assessment and diagnostic procedures. The first hospital admission allows diagnosis and psychopharmacological treatment to be established. In our population, aggressive behaviors were rather frequent, although most commonly verbal. Psychiatric symptoms, as evaluated by psychiatrists and patients, improved significantly from admission to discharge both for FPA and non-FPA patients

    ALMS1-Deficient Fibroblasts Over-Express Extra-Cellular Matrix Components, Display Cell Cycle Delay and Are Resistant to Apoptosis

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    Alström Syndrome (ALMS) is a rare genetic disorder (483 living cases), characterized by many clinical manifestations, including blindness, obesity, type 2 diabetes and cardiomyopathy. ALMS is caused by mutations in the ALMS1 gene, encoding for a large protein with implicated roles in ciliary function, cellular quiescence and intracellular transport. Patients with ALMS have extensive fibrosis in nearly all tissues resulting in a progressive organ failure which is often the ultimate cause of death. To focus on the role of ALMS1 mutations in the generation and maintenance of this pathological fibrosis, we performed gene expression analysis, ultrastructural characterization and functional assays in 4 dermal fibroblast cultures from ALMS patients. Using a genome-wide gene expression analysis we found alterations in genes belonging to specific categories (cell cycle, extracellular matrix (ECM) and fibrosis, cellular architecture/motility and apoptosis). ALMS fibroblasts display cytoskeleton abnormalities and migration impairment, up-regulate the expression and production of collagens and despite the increase in the cell cycle length are more resistant to apoptosis. Therefore ALMS1-deficient fibroblasts showed a constitutively activated myofibroblast phenotype even if they do not derive from a fibrotic lesion. Our results support a genetic basis for the fibrosis observed in ALMS and show that both an excessive ECM production and a failure to eliminate myofibroblasts are key mechanisms. Furthermore, our findings suggest new roles for ALMS1 in both intra- and extra-cellular events which are essential not only for the normal cellular function but also for cell-cell and ECM-cell interactions

    Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

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    <p>Abstract</p> <p>Background</p> <p>The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.</p> <p>Methods</p> <p>A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.</p> <p>Results</p> <p>Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.</p> <p>Conclusion</p> <p>Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.</p

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Acromegalic Cardiopathy - A Left-ventricular Scintigraphic Study

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    In order to study ''acromegalic cardiomyopathy'', cardiac function was examined, using gated radionuclide ventriculography, in 18 acromegalic patients and 21 control subjects with no clinical evidence of cardiac involvement. In these acromegalic subjects, while the Ejection Fraction (EF) did not appear to be significantly different, the Peak Filling Rate (PFR) was reduced while the Time to Peak Filling Rate (TPFR) resulted significantly greater than in control subjects. These findings indicate that chronic growth hormone (GH) hypersecretion, as observed in acromegaly, deteriorate the cardiac ventricular relaxation (diastolic phase) while it has no influence on contractility (systolic phase)
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