Herpes Simplex Virus-2 Glycoprotein Interaction with HVEM Influences Virus-Specific Recall Cellular Responses at the Mucosa

Infection of susceptible cells by herpes simplex virus (HSV) requires the interaction of the HSV gD glycoprotein with one of two principal entry receptors, herpes virus entry mediator (HVEM) or nectins. HVEM naturally functions in immune signaling, and the gD-HVEM interaction alters innate signaling early after mucosal infection. We investigated whether the gD-HVEM interaction during priming changes lymphocyte recall responses in the murine intravaginal model. Mice were primed with attenuated HSV-2 expressing wild-type gD or mutant gD unable to engage HVEM and challenged 32 days later with virulent HSV-2 expressing wild-type gD. HSV-specific CD8+ T cells were decreased at the genital mucosa during the recall response after priming with virus unable to engage HVEM but did not differ in draining lymph nodes. CD4+ T cells, which are critical for entry of HSV-specific CD8+ T cells into mucosa in acute infection, did not differ between the two groups in either tissue. An inverse association between Foxp3+ CD4+ regulatory T cells and CD8+ infiltration into the mucosa was not statistically significant. CXCR3 surface expression was not significantly different among different lymphocyte subsets. We conclude that engagement of HVEM during the acute phase of HSV infection influences the antiviral CD8+ recall response by an unexplained mechanism

Role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry

Cardiac ventricular tachycardia (VT) is a life-threatening arrhythmia consisting of a well organized structure of reentrant electrical excitation pathways. Understanding the generation and maintenance of the reentrant mechanisms, which lead to the onset of VT induced by premature beats in presence of infarct scar, is one of the most important issues in current electrocardiology. We investigate, by means of numerical simulations, the role of infarct scar dimension, repolarization properties and anisotropic fiber structure of scar tissue border zone (BZ) in the genesis of VT. The simulations are based on the Bidomain model, a reaction-diffusion system of Partial Differential Equations, discretized by finite elements in space and implicit-explicit finite differences in time. The computational domain adopted is an idealized left ventricle affected by an infarct scar extending transmurally. We consider two different scenarios: i) the scar region extends along the entire transmural wall thickness, from endocardium to epicardium, with the exception of a BZ region shaped as a central sub-epicardial channel (CBZ); ii) the scar region extends transmurally along the ventricular wall, from endocardium to a sub-epicardial surface, and is surrounded by a BZ region (EBZ). In CBZ simulations, the results have shown that: i) the scar extent is a crucial element for the genesis of reentry; ii) the repolarization properties of the CBZ, in particular the reduction of IKs and IKr currents, play an important role in the genesis of reentrant VT. In EBZ simulations, since the possible reentrant pathway is not assigned a-priori, we investigate in depth where the entry and exit sites of the cycle of reentry are located and how the functional channel of reentry develops. The results have shown that: i) the interplay between the epicardial anisotropic fiber structure and the EBZ shape strongly affects the propensity that an endocardial premature stimulus generates a cycle of reentry; ii) reentrant pathways always develop along the epicardial fiber direction; iii) very thin EBZs rather than thick EBZs facilitate the onset of cycles of reentry; iv) the sustainability of cycles of reentry depends on the endocardial stimulation site and on the interplay between the epicardial breakthrough site, local fiber direction and BZ rim

Adipose-derived stem/stromal cells in kidney transplantation: Status quo and future perspectives

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia-reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted

Deformation Sequence and Paleofluids in Carbonate Buckle Folds Under Transpression (Pag Anticline, External Dinarides, Croatia)

Contractional deformation structures at the front of transpressional orogens display complex three-dimensional geometries deviating from the interpretative templates commonly applied in thrust belts. Accordingly, detailed constraints on deformation patterns and associated paleofluid circulation are desirable, especially for fracture geometry and permeability predictive purposes. The Pag anticline, which is located in the Dinaric fold and thrust belt, provides an appropriate field site for studying fold- and fault-related deformation structures in a transpressive setting. We performed a multiscale structural analysis together with petrographic and stable isotope characterization of the deformation-related calcite cements. Structural mapping suggests that the Pag anticline is a detachment fold developed mainly by buckling, since large-scale thrust faults are absent. Fold tightening in a transpressive setting produced a complex deformational structure including two sets of N-S right-lateral and E-W left-lateral late-stage strike-slip fault sets trending oblique to the NW-SE fold axis. The pre-folding deformation pattern includes incipient normal faults likely related to the forebulge stage, veins and stylolites coherent with NE-SW layer parallel shortening contraction in a strike-slip regime, and metric to decametric scale conjugate thrusts coherent with layer parallel shortening in a compressive regime. Buckle folding preceded propagation of a series of accommodation structures during fold tightening. Petrographic and isotopic data indicate meteoric alteration of the Cretaceous platform carbonates in the prefolding stage, likely due to forebulge subaerial exposure. Layer parallel shortening and early syn-folding veins involved formational fluids resulting from mixed marine and meteoric fluids during folding at shallow burial conditions. Eventually, meteoric fluid infiltrated again along strike-slip faults, acting as cross-formational conduits in the postfolding stage

Assetto ormonale tiroideo in pazienti efficacemente rivascolarizzati per infarto miocardico acuto e sopraslivellamento del tratto ST.

un alterato assetto funzionale tiroideo, caratterizzato dalla presenza di una sindrome da bassa T3 (LT3S), rappresenta un reperto di frequente osservazione nei pazienti ricoverati presso i reparti di terapia intensiva per infarto miocardico acuto. Il significato di tale sindrome nel decorso della malattia non ? tuttavia finora ben chiarito