SARS-CoV-2 and Viral Sepsis: Immune Dysfunction and Implications in Kidney Failure

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), first emerged in Wuhan, China. The clinical manifestations of patients infected with COVID-19 include fever, cough, and dyspnea, up to acute respiratory distress syndrome (ARDS) and acute cardiac injury. Thus, a lot of severe patients had to be admitted to intensive care units (ICU). The pathogenic mechanisms of SARS-CoV-2 infection are mediated by the binding of SARS-CoV-2 spikes to the human angiotensin-converting enzyme 2 (ACE-2) receptor. The overexpression of human ACE-2 is associated with the disease severity in SARS-CoV-2 infection, demonstrating that viral entry into cells is a pivotal step. Although the lung is the organ that is most commonly affected by SARS-CoV-2 infection, acute kidney injury (AKI), heart dysfunction and abdominal pain are the most commonly reported co-morbidities of COVID-19. The occurrence of AKI in COVID-19 patients might be explained by several mechanisms that include viral cytopathic effects in renal cells and the host hyperinflammatory response. In addition, kidney dysfunction could exacerbate the inflammatory response started in the lungs and might cause further renal impairment and multi-organ failure. Mounting recent evidence supports the involvement of cardiovascular complications and endothelial dysfunction in COVID-19 syndrome, in addition to respiratory disease. To date, there is no vaccine, and no specific antiviral medicine has been shown to be effective in preventing or treating COVID-19. The removal of pro-inflammatory cytokines and the shutdown of the cytokine storm could ameliorate the clinical outcome in severe COVID-19 cases. Therefore, several interventions that inhibit viral replication and the systemic inflammatory response could modulate the severity of the renal dysfunction and increase the probability of a favorable outcome

Rockfall Hazard Analysis at Small Scale: A Numerical Study for the Estimation of Representative Slope Parameters

The identification of rockfall-affected areas depends on a large number of stochastic variables influencing both triggering and propagation phases. Therefore, rockfall hazard assessment presents huge uncertainties linked to the various scales of analysis. At the small scale (e.g. valley scale), a quick evaluation of rockfall hazard zones is generally required in order to highlight the most critical situations where more detailed analyses should be carried out. The Cone Method (Jaboyedoff and Labiouse 2011), recently implemented in the QPROTO plugin for QGIS, allows to reach this goal with simplified geometrical considerations. In a 3D analysis, the energy line angle and the lateral spreading angle α define a cone of propagation whose apex is located in the rockfall source point. The most significant issue in using the plugin is the evaluation of these angles, which must be defined by the users to consider all the rockfall dissipative processes included in the energy line method (Evans and Hungr 1993). In this paper a study concerning the influence of slope properties (forest coverage and slope inclination) and block characteristics (shape and volume) is proposed, in order to provide to the users of the plugin a preliminary dataset of calibrated angles

Endothelial dysfunction and renal fibrosis in endotoxemia-induced oliguric kidney injury: possible role of LPS binding protein

The pathophysiology of endotoxemia-induced acute kidney injury (AKI) is characterized by an intense activation of the host immune system and renal resident cells by lipopolysaccharide (LPS) and derived proinflammatory products. However, the occurrence of renal fibrosis in this setting has been poorly investigated. The aim of the present study was to investigate the possible association between endothelial dysfunction and acute development of tissue fibrosis in a swine model of LPS-induced AKI. Moreover, we studied the possible effects of coupled plasma filtration adsorption (CPFA) in this setting

Biofilters and biosensors

Sepsis is the leading cause of morbidity and mortality in intensive care units (ICU). Acute renal failure (ARF) is a common condition, affecting approximately 5% of all hospitalized patients and up to 20% of critically ill patients. The combination of ARF and sepsis is associated with 75% mortality. Hyperglycemia and an increase in plasma lactate concentration are markers of poor prognosis in patients with sepsis; they often precede the onset of multiple organ dysfunction and ARF. Direct online measurement by means of amperometric biosensors would allow the early detection of increasing levels of both glucose and lactate, as well as the possibility to maintain glucose within a well-defined range. Current standards of care in ARF require synthetic membranes that substitute the small solute clearance function of the renal glomerulus, but they do not replace the transport, metabolic and endocrine functions of the renal proximal tubule cells. The application of cell therapy to the successful process of hemofiltration may therefore improve the poor prognosis of patients with ARF in the ICU. An extracorporeal bioartificial kidney consisting of a conventional hemofilter connected to a renal tubule assist device has demonstrated both in animal models of ARF and in phase I/II clinical trials its ability to successfully replace the filtration, transport, metabolic, and endocrine functions of the kidney. To improve the outcome of septic patients with ARF, multidisciplinary interactions and cooperation between basic, clinical and industrial researchers are mandatory; the development of new artificial or biological devices may allow online monitoring of biological parameters and better treatment of septic syndrome and related systemic complications

Breaking the mould: Casting on the nanometre scale

The rational design of materials by organization at the atomic scale is attractive for delivering increased functionality, but there are practical difficulties in such precise construction. Nanocasting is an emerging technique that provides one way of solving the problem