Detection of a-to-i rna editing in sars-cov-2

ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus–host interactions could be relevant to identify potential targets for therapeutic interventions

Treatment volume of aedes albopictus with X rays generated from electrons

Irradiation is a common method used for sterilizing objects in several fields. In the entomology sector, insects are sterilized through irradiation and released in to the wild to sexually compete with the population at large reducing the chance for reproduction. This practice is the Sterile Insect Technique (SIT). Traditionally irradiation sources for SIT purpose are radioisotopes but many reasons compelled to getting efforts to develop other radiative technologies. Since gamma rays and electrons have similar sterilizing effects, the choice of source for SIT irradiation is based on considerations about penetration and environmental factors. Gamma irradiators are usually simpler to operate, and less expensive, than electron accelerators, at least within the range of power required for SIT applications. Currently, the increased difficulties to manage and ship radioisotopes is being successfully resolved by the introduction of novel X-ray irradiators that enable a safer use of irradiator machines and procedures for SIT applications. In the ENEA Frascati research center we developed irradiators for clinical radiotherapy consisting in a radiation converter from electrons to X-rays. Since X-rays penetrate deeper than the electrons from which they are generated, we used this technology in a configuration that delivers a uniform dose on large targets to irradiate insects for SIT aim. In this topic, we gained practical experience working with Aedes albopictus, a mosquito vector of various tropical diseases such as dengue and zika. Several dosimetric studies have been conducted to achieve male sterility without affecting male mating competitiveness in comparison with untreated males. Lower doses have been also tested on an Ae. albopictus strain modified with the bacterium Wolbachia, which also determines male sterility, to sterilize the females eventually escaping the sexing procedures preliminary to the releases of the males

Delusional themes across affective and non-affective psychoses

The current debate about the diagnostic significance of delusion revolves around two positions. The neurocognitive position conceives delusion as a non-specific, though polymorphic, symptom. The psychopathological position views features of delusion such as content and structure as having meaningful connections with diagnostic entities. This study aims at contributing to this debate by examining the association between delusional themes and diagnosis in a sample of 830 adult psychotic patients. All diagnoses were made by experienced psychiatrists according to DSM-IV or ICD-10 criteria, and in 348 patients were established with the SCID-I. All patients were administered the Brief Psychiatric Rating Scale (BPRS). In each patient, the presence of somatic delusions and delusions of guilt, grandiosity, and persecution was determined by examining the scores on relevant BPRS items. Delusions of guilt were almost pathognomonic for a psychotic depressive condition (psychotic major depression 40%; psychotic bipolar depression 30%; depressed schizoaffective disorder 8%; bipolar and schizoaffective mixed states 6 and 7%, respectively). Only 1% of patients with schizophrenia and no patient with delusional disorder or bipolar or schizoaffective manic state showed such delusions. The difference between unipolar and bipolar depression and the other diagnostic groups was highly significant. Delusions of grandiosity characterized mostly patients with manic symptoms (bipolar mania 20%; bipolar mixed states 19%; manic schizoaffective disorder 10%). They were observed significantly more often in bipolar mania than in schizophrenia (7%). Persecutory delusions were broadly distributed across diagnostic categories. However, they were significantly more frequent among patients with schizophrenia and delusional disorder compared with depressed and manic patients. Somatic delusions were also observed in all diagnostic groups, with no group standing out as distinct from the others in terms of an increased prevalence of somatic delusions. Our findings suggest a middle position in the debate between the neurocognitive and the psychopathological approaches. On the one hand, the widespread observation of persecutory delusions suggests the usefulness of searching for non-specific pathogenic mechanisms. On the other hand, the association between some delusional contents and psychiatric diagnosis suggests that a phenomenological analysis of the delusional experience may be a helpful tool for the clinician in the diagnostic process

Combined treatment with amphotericin-B and granulocyte transfusion from G-CSF-stimulated donors in an aplastic patient with invasive aspergillosis undergoing bone marrow transplantation.

Granulocyte transfusions from G-CSF stimulated donors were added to standard anti-infective treatment in preparation for and during allogeneic bone marrow transplantation in a young man affected by very severe acute aplastic anemia and invasive aspergillosis. Nine concentrates with a mean neutrophil content of 18.7x109/L (2.6x 108/kg patient b.w.) were transfused before and after marrow infusion. An impressive clinical improvement was noticed after each granulocyte transfusion, although this was not always paralleled by a neutrophil increase in the peripheral blood. Engraftment (N>0.5x109/L and PIt >25x109/L) was verified at +16 and +40 days, respectively. The patient is currently in complete hematological and microbiological remission 14 months after transplantation. Granulocyte apheresis from G-CSF stimulated donors provides a high number of activated neutrophils. At the dose given (300 μg/day) donor tolerance to G-CSF was excellent. This new approach is indicated when life-threatening infections develop in patients exposed to prolonged severe neutropenia

Small bowel infarction by Aspergillus.

Primary gut involvement by Aspergillus is a rare and often fatal complication of intensive antileukemic therapy. We describe the case of an adult patient affected by acute leukemia who developed a small bowel fungal thromboembolism without radiographic evidence of lung involvement during the post-induction aplastic phase. The diagnosis was made histologically at laparotomy performed for small bowel perforation. The patient died a week later in spite of amphotericin-B treatment and neutrophil recovery. Anti- Aspergillus prophylaxis and early introduction of amphotericin-B in the treatment of febrile neutropenia is probably advisable in all cases of AML

Low-dose interleukin-2 for treating postautologous transplant cytogenetic abnormality recurrency in a case of acute myeloid leukemia with hyperdiploidy.

Adoptive immunotherapy and/or immunostimulation may be effective in treating early phases of leukemia relapsing after allogeneic transplant. Donor lymphocyte infusion (DLI) is an established treatment for cytogenetic relapse of chronic myeloid leukemia (CML) after unmanipulated or T-cell–depleted bone marrow transplant (BMT)1; favorable results have also been reported in a few cases of initial posttransplant relapse of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).2 A graft-versus-leukemia (GVL) effect as part of a manifest or occult DLI-elicited graft-versus-host disease (GVHD) is thought to be the reason for these favorable results. For patients who had received autologous transplant, attempts to elicit an antineoplastic effect by immunostimulation have been made using in vitro interleukin-2 (IL-2)–activated autologous lymphocytes and/or IL-2 in vivo administration.34 We report on the successful use of subcutaneous (sc) low-dose IL-2 in a patient suffering from AML with recurrence of cytogenetic abnormalities after autografting

CD34+ enriched donor lymphocyte infusions in a case of pure red cell aplasia and late graft failure after major ABO-incompatible bone marrow transplantation

A variety of immunohematological complications may occur after ABO-incompatible BMT. We report a CML patient (blood group O) who received a BMT from an HLA-identical sibling (blood group AB). The transplant was followed by normal myeloid and megakaryocytic engraftment, but erythroblastopenia persisted for more than 200 days after BMT. By bone marrow culture studies, a complement-dependent serum inhibitor of hemopoiesis was detected, suggesting immunological inhibition of erythropoiesis. The patient was resistant to a number of treatments such as intravenous gamma-globulins, prednisolone and high-dose erythropoietin. Full engraftment with normal blood counts and marrow cellularity was achieved after two dose-escalating CD34+-enriched donor lymphocyte infusions (DLI). This experience suggests that CD34+-enriched DLI may be an effective treatment for patients with delayed engraftment or late graft failure due to major ABO-incompatibility

Fine-needle aspiration biopsy and flow cytometry immunophenotyping of lymphoid and myeloproliferative disorders of the spleen.

BACKGROUND: Flow cytometry (FC) is a useful adjunct to fine-needle aspiration biopsy (FNAB) in the evaluation of lymphoproliferative disorders. The application of FC to FNAB of the spleen (sFNAB) is reported. METHODS: Flow cytometry was performed on 18 sFNAB collected over 3 years. The series comprised 10 cases of non- Hodgkin lymphomas (NHL), 2 cases insufficient for diagnosis, 2 cases of reactive hyperplasia (RH), and 4 cases of myeloid metaplasia (MM). FNAB was performed under ultrasound guidance using a 22-gauge needle. One or two passes were sufficient to prepare a conventional smear that was immediately evaluated to select the cases studied and to prepare a cell suspension for FC. The following fluoresceinated antibodies were used: CD3, CD19/kappa/lambda, FMC7/CD23/CD19, Bcl-2, and CD13/HLA-DR. In six cases, cytospins were also prepared for immunocytochemistry and were tested for CD20 (L26), CD45Ro, and kappa and lambda light chain expression. RESULTS: Flow cytometry contributed to the diagnosis of all cases of NHL by assessing light chain restriction. The specific subtype was also diagnosed by CD19/CD5 and CD 19/CD10 coexpression in two cases. Flow cytometry quantified the percentage of myeloid cells in MM cases and contributed to the cytologic diagnosis showing a polyclonal light chain expression in RH cases.Immunocytochemistry was effective and concordant in four cases. Patients tolerated the sFNAB well and no complications were reported. Cytologic and FC diagnoses were confirmed by follow-up and by histologic evaluation in cases in which splenectomy was performed for therapeutic purposes. CONCLUSION: Flow cytometry applied to sFNAB corroborates the cytologic diagnosis in lymphoid and myeloproliferative disorders of the spleen and allows therapeutic decisions avoiding splenectomy