Functional profile of cytomegalovirus (CMV)-specific CD8+ T cells and kinetics of NKG2C+ NK cells associated with the resolution of CMV DNAemia in allogeneic stem cell transplant recipients

Immune mechanisms involved in control of cytomegalovirus (CMV) infection in the allogeneic stem cell transplantation setting have not been fully disclosed. CMV pp65 and IE-1-specific CD8(+) T cells expressing IFN-γ, TNF-α, and CD107a, alone or in combination, and NKG2C(+) NK cells were prospectively enumerated during 13 episodes of CMV DNAemia. The expansion of monofunctional and polyfunctional CD8(+) T cells was associated with CMV DNAemia clearance. The size and functional diversity of the expanding CD8(+) T-cell population was greater in self-resolved episodes than in episodes treated with antivirals. These differences were related to the magnitude of expansion of cognate antigen IFN-γ CD4(+) T cells. The resolution of CMV DNAemia was associated frequently with a marked expansion of both CD56(dim) /CD16(+) NK cells and NKG2C(+) CD56(bright) /CD16(-) NK cells. The data lend support to the role of polyfunctional CD8(+) T cells in controlling CMV replication in the allogeneic stem cell transplantation setting, and suggest that NKG2C(+) NK cells may be involved critically in the resolution of CMV DNAemia episodes.     

Towards a multifactorial approach for prediction of bipolar disorder in at risk populations

BackgroundThe high prevalence, recurrence rate, chronicity, and illness burden in bipolar disorder (BD) are well documented. Moreover, insufficient response with conventional pharmacological and manual-based psychosocial interventions, as well as evidence of illness progression and acceleration, invite the need for early detection and primary prevention.MethodsHerein we comprehensively review extant studies reporting on a bipolar prodrome. The overarching aim is to propose a predictive algorithm (i.e. prediction of BD in at-risk populations) integrating genetic (i.e. family history), environmental (e.g. childhood maltreatment) and biological markers (i.e. BDNF, inflammatory and oxidative stress markers). Computerized databases i.e. Pubmed, PsychInfo, Cochrane Library and Scielo were searched using the followed terms: bipolar disorder cross-referenced with prodromal, preclinical, at risk mental states, clinical high risk, ultra high risk, biomarkers, brain-derived neurotrophic factor, inflammation, cytokines, oxidative stress, prediction and predictive model.ResultsAvailable evidence indicates that a prodrome to bipolar disorder exists. Commonly encountered features preceding the onset of a manic episode are affective lability, irritability, anger, depression, anxiety, substance use disorders, sleep disorders, as well as disturbances in attention and cognition. Non-specificity and insufficient sensitivity have hampered the development of an adequate prediction algorithm.LimitationsLimitations include biases associated with retrospective studies, poor characterization of clinical high risk, inadequacy of prospective studies regarding sample selection and absence of specificity of risk states.ConclusionWe propose a hypothetical prediction algorithm that is combinatorial in approach that attempts to integrate family history, early adversity, and selected biomarkers.     

Intraoperative Epidural Analgesia Prevents the Early Proinflammatory Response to Surgical Trauma. Results from a Prospective Randomized Clinical Trial of Intraoperative Epidural Versus General Analgesia

Background  

The intraoperative epidural analgesia (EA) has the potential to reduce stress response to surgical trauma which induces a transient immunoactivation that has a negative impact on the outcome. This study investigates the effect of intraoperative EA versus intravenous analgesia (IA) on the immune function.     

Atypical lesions as a sign of cutaneous dissemination of visceral leishmaniasis in a human immunodeficiency virus-positive patient simultaneously infected by two viscerotropic Leishmania species

Leishmaniasis is considered an emerging opportunistic disease in human immunodeficiency virus (HIV)-infected patients who have considerably variable clinical presentation. We report a patient with visceral leishmaniasis who had unexpected clinical aspects (atypical cutaneous lesions appearing after long-term evidence of visceral parasites). The patient had hepatoesplenomegaly in the absence of fever, but was otherwise generally healthy. The HIV viral load was low despite severe immunossupression (low lymphocyte proliferation and low level of interferon-γ, concomitant with a high lymphocyte activation status). Surprisingly, two Leishmania strains were isolated from his bone marrow (typical L. infantum sequence MON-1, type A) and skin (L. donovani MON-2 sequence); this second strain had not been previously identified in Brazil. The association of visceral leishmaniasis and HIV/acquired immunodeficiency syndrome is a largely unknown disease, particularly in areas in which leishmaniasis is not endemic. Such atypical cases indicate that this disease can be undiagnosed in clinical settings.     

Microvascular dysfunction in the spectrum of coronary instability

The term "coronary instability" commonly refers to the sequence of events that lead from plaque erosion or rupture to the occurrence of acute coronary syndromes (ACS). However, evidence indicates that coronary microvascular dysfunction plays a relevant pathophysiologic and prognostic role in the setting of ACS, both in ST-segment elevation myocardial infarction and in non-ST-segment elevation ACS. Our group have recently demonstrated that Tako-Tsubo syndrome, which clinically mimics ACS, is sustained by a common pathophysiologic mechanism represented by reversible coronary microvascular dysfunction. Given this evidence, we propose a reappraisal of the concept of coronary instability, extending this notion from the dramatic event represented by plaque erosion or rupture to a more diffuse process that can acutely affect each segment of the coronary circulation.