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Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated in the outcomes of respiratory virus infections. We report that RSV infection triggers necroptosis in primary mouse macrophages and human monocytes in a RIPK1-, RIPK3- and MLKL-dependent manner. Moreover, necroptosis pathways are harmful to RSV clearance from alveolar macrophages. Additionally, Ripk3 -/- mice were protected from RSV-induced weight loss and presented with reduced viral loads in the lungs.Alveolar macrophage depletion also protected mice from weight loss and decreased lung RSV virus load. Importantly, alveolar macrophage depletion abolished the upregulation of Ripk3 and Mlkl gene expression induced by RSV infection in the lung tissue.Autocrine tumor necrosis factor (TNF)-mediated RSV-triggered macrophage necroptosis and necroptosis pathways were also involved in TNF secretion even when macrophages were committed to cell death, which can worsen lung injury during RSV infection. In line, Tnfr1 -/- mice had a marked decrease in Ripk3 and Mlkl gene expression and a sharp reduction in the numbers of necrotic alveolar macrophages in the lungs. Finally, we provide evidence that elevated nasal levels of TNF are associated with disease severity in infants with RSV bronchiolitis.We propose that targeting TNF and/or the necroptotic machinery may be valuable therapeutic approaches to reduce the respiratory morbidity caused by RSV infection in young children., Competing Interests: Conflict of interest: L.D. Santos reports grants from CAPES, during the conduct of the study. Conflict of interest: K.H. Antunes has nothing to disclose. Conflict of interest: S.P. Muraro has nothing to disclose. Conflict of interest: G.F. de Souza has nothing to disclose. Conflict of interest: A.G. da Silva has nothing to disclose. Conflict of interest: J.S. Felipe has nothing to disclose. Conflict of interest: L.C. Zanetti has nothing to disclose. Conflict of interest: R.S. Czepielewski has nothing to disclose. Conflict of interest: K. Magnus has nothing to disclose. Conflict of interest: M. Scotta has nothing to disclose. Conflict of interest: R. Mattiello has nothing to disclose. Conflict of interest: F. Maito has nothing to disclose. Conflict of interest: A.P. Duarte de Souza has nothing to disclose. Conflict of interest: R. Weinlich has nothing to disclose. Conflict of interest: M.A.R. Vinolo has nothing to disclose. Conflict of interest: B.N. Porto reports grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), during the conduct of the study., (Copyright ©ERS 2021.)

Respiratory syncytial virus (RSV)-specific CD8(+) T cell responses do not protect against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs memory CD8(+) T cell differentiation. Our hypothesis was that RSV inhibits the formation of CD8(+) T cells memory responses through mTOR activation. To explore this, human and mouse T cells were used. RSV induced mTOR phosphorylation at Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using rapamycin. RSV-infected children presented higher mTOR gene expression on nasal washes comparing to children infected with metapneumovirus and rhinovirus. In addition, RSV-infected infants presented a higher frequency of CD8(+) pmTORser2448(+) T cells in nasal washes compared to RSV-negative infants. Rapamycin treatment increased the frequency of mouse CD8 RSV-M282-90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. These data demonstrate that RSV is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection., (© 2015 British Society for Immunology.)

Background: The purpose of this study was to provide preliminary data on the effects of paroxetine and amisulpride on depressive dimensions, analyzed by factor analysis, in dysthymic patients., Methods: One hundred and eighteen patients with DSM IV criteria for DD without concurrent major depression were enrolled in this 8-week, open study, and 100 completed it. Symptom dimensions were identified by principal components analysis with the SAS Factor procedure., Results: Results of the symptom rating scales indicated that both drugs were equally effective. Response rate was 65% both in the paroxetine and the amisulpride group and the proportions of patients achieving a final HRSD score < or =7 were 46.7 and 55%, respectively. MADRS factor analysis identified two factors at baseline: the first corresponding to the global severity of depression and the second to somatic symptoms. After 8 weeks of treatment only one factor could be substantiated. At week 4 both paroxetine and amisulpride produced significant improvements on factor 1 while at week 8 mean changes of factor 1 were greater in the amisulpride-treated patients., Limitations: The main limitation was the open-label design., Conclusions: Both paroxetine and amisulpride appear to be effective in the short-term management of DD, improving its most characteristic symptoms., (Copright 2002 Elsevier Science BV.)

Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.

A case of intracranial saccular aneurysm with intracerebral haematoma occurring in early childhood and presenting with sudden loss of consciousness and right hemiparesis is reported. The aneurysm was located in the opercular portion of the left middle cerebral artery. Surgery, besides removing the intracerebral haematoma, involved clipping and complete removal of the aneurysmal sac. The child made an uneventful recovery, and he is completely safe after 40 months. Microscopic examination of the lesion shows disruption of the normal sequence of the original layers, with widespread inflammatory cells.