A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Case report: Molecular characterization of adult atypical teratoid rhabdoid tumor and review of the literature

Background and importanceAtypical teratoid rhabdoid tumors (ATRTs) are typically aggressive pediatric tumors with a median survival of 11 months. Due to the paucity of cases in adults, the clinical behavior of these pathologies is not well understood. Here we present the case of a 41-year-old female patient with postoperative hyperprogression of a sellar ATRT and provide a detailed description of the molecular composition of this tumor, the protocol used to treat this patient, and the ultimate outcome of this patient.Clinical presentationThe patient is a 41-year-old woman who presented with headaches and double vision. MRI revealed a sellar/suprasellar mass with involvement of bilateral cavernous sinuses. Following the quick symptom progression, resection of the tumor with exploration of the bilateral cavernous sinuses was performed, with a final pathologic diagnosis of ATRT-MYC, a known subtype of ATRT. The tumor recurred within 1 month of surgery, attaining a size equivalent to its preoperative state. Postoperatively, the patient received craniospinal radiation and adjuvant chemotherapy with an excellent response but had a recurrence of the tumor in the brainstem 1 year after her diagnosis and died 13 months after presentation.DiscussionSellar ATRT in adults is an exceedingly rare entity. The detailed description of our case highlights the aggressiveness of these tumors and the utility of postoperative chemotherapy and radiation, but also the inevitable progression of these tumors along the craniospinal axis.ConclusionSellar ATRTs should be considered in the differential diagnosis of a sellar/suprasellar mass, especially in women in their 40s. Emphasis should be placed on accurate diagnosis and quick postoperative recovery with early initiation of adjuvant radiation and chemotherapy

Εξέταση επιρροής αναερόβιου φρεατίου επιλογής στον έλεγχο της νηματοειδούς διόγκωσης σε συστήματα ενεργού ιλύος

141 σ.Η κακή καθιζησιμότητα ιλύος στις δεξαμενές τελικής καθίζησης συστημάτων ενεργού ιλύος αποτελεί σημαντικό λειτουργικό πρόβλημα στις εγκαταστάσεις επεξεργασίας λυμάτων σε παγκόσμια κλίμακα. Στόχος της έρευνας είναι η διερεύνηση της επιρροής της συνεργασίας κινητικής και μεταβολικής επιλογής του αναερόβιου φρεατίου στο Πειραματικό Σύστημα για τον έλεγχο της ανάπτυξης των νηματοειδών μικροοργανισμών και των προβλημάτων νηματοειδούς διόγκωσης κατ' επέκταση.On a global scale, poor sludge settling into final settling tanks in activated sludge systems is an important operating problem in wastewater treatment plants. The research aims to investigate the influence of cooperating kinetic and metabolic pressures that the anaerobic selector tank applies at the Experimental System, in order to control the growth of filamentous bacteria and filamentous bulking problems by extension.Βασίλης Α. Μαθιό

The Journal of Consumer Policy Outstanding Reviewer Award 2011

n/