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Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists’ increased adherence to guidelines and “bundles”. The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment.Key MessagesSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease.At least half of patients affected by sepsis are admitted to Internal Medicine wards.Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization. [ABSTRACT FROM PUBLISHER]

The amyloid hypothesis posits that the amyloid-beta (Aβ) protein precedes and requires microtubule-associated protein tau in a sort of trigger-bullet mechanism leading to Alzheimer's disease (AD) pathology. This sequence of events has become dogmatic in the AD field and is used to explain clinical trial failures due to a late start of the intervention when Aβ already activated tau. Here, using a multidisciplinary approach combining molecular biological, biochemical, histopathological, electrophysiological, and behavioral methods, we demonstrated that tau suppression did not protect against Aβ-induced damage of long-term synaptic plasticity and memory, or from amyloid deposition. Tau suppression could even unravel a defect in basal synaptic transmission in a mouse model of amyloid deposition. Similarly, tau suppression did not protect against exogenous oligomeric tau-induced impairment of long-term synaptic plasticity and memory. The protective effect of tau suppression was, in turn, confined to short-term plasticity and memory. Taken together, our data suggest that therapies downstream of Aβ and tau together are more suitable to combat AD than therapies against one or the other alone. [ABSTRACT FROM AUTHOR]

Astrocytes provide metabolic support for neurons and modulate their functions by releasing a plethora of neuroactive molecules diffusing to neighboring cells. Here we report that astrocytes also play a role in cortical neurons' vulnerability to Herpes simplex virus type-1 (HSV-1) infection through the release of extracellular ATP. We found that the interaction of HSV-1 with heparan sulfate proteoglycans expressed on the plasma membrane of astrocytes triggered phospholipase C-mediated IP 3 -dependent intracellular Ca 2+ transients causing extracellular release of ATP. ATP binds membrane purinergic P2 receptors (P2Rs) of both neurons and astrocytes causing an increase in intracellular Ca 2+ concentration that activates the Glycogen Synthase Kinase (GSK)-3β, whose action is necessary for HSV-1 entry/replication in these cells. Indeed, in co-cultures of neurons and astrocytes HSV-1-infected neurons were only found in proximity of infected astrocytes releasing ATP, whereas in the presence of fluorocitrate, an inhibitor of astrocyte metabolism, switching-off the HSV-1-induced ATP release, very few neurons were infected. The addition of exogenous ATP, mimicking that released by astrocytes after HSV-1 challenge, restored the ability of HSV-1 to infect neurons co-cultured with metabolically-inhibited astrocytes. The ATP-activated, P2R-mediated, and GSK-3-dependent molecular pathway underlying HSV-1 infection is likely shared by neurons and astrocytes, given that the blockade of either P2Rs or GSK-3 activation inhibited infection of both cell types. These results add a new layer of information to our understanding of the critical role played by astrocytes in regulating neuronal functions and their response to noxious stimuli including microbial agents via Ca 2+ -dependent release of neuroactive molecules., (© 2020 Wiley Periodicals LLC.)