Molecular Mechanisms of AKI in the Elderly: From Animal Models to Therapeutic Intervention

Acute kidney injury (AKI), a critical syndrome characterized by a sudden reduction of renal function, is a common disorder among elderly patients particularly in Intensive Care Unit (ICU). AKI is closely associated with both short- and long-term mortality and length of hospital stay and is considered a predictor of chronic kidney disease (CKD). Specific hemodynamic, metabolic, and molecular changes lead to increased susceptibility to injury in the aged kidney; therefore, certain causes of AKI such as the prerenal reduction in renal perfusion or vascular obstructive conditions are more common in the elderly; moreover, AKI is often multifactorial and iatrogenic. Older patients present several comorbidities (diabetes, hypertension, heart failure) and are exposed to multiple medical interventions such as the use of nephrotoxic contrasts media and medications, which can also trigger AKI. Considering the emerging relevance of this condition, prevention and treatment of AKI in the elderly should be crucial in the internist and emergency setting. This review article summarizes the incidence, the risk factors, the pathophysiology, the molecular mechanisms and the strategies of prevention and treatment of AKI in elderly patients

A method for automation software design of mechatronic systems in manufacturing

The fast globalization process of the last decade required companies to optimize internal processes. Additionally, customers requirements are becoming more and more specific, requiring strong customization. In the mechatronic field, the automation software development takes a wide percentage of the overall designing time, due to the lack of structured design processes (specially for small systems) and code reuse. This paper aims to define a first structured approach for the automation software development of small manufacturing systems. The proposed solution is based on concepts like modularization and encapsulation, trying to build a one-to-one relationship between the physical mechatronic object and its control software module. Each module embeds the control software and other information related to the HMI, the documentation and the risk assessment. The introduced method has been implemented on a real small manufacturing system (an industrial manipulator). The components that form the device have been identified and implemented as modules. The design phase becomes, then, a drag and drop composition of such modules, controlled by a state machine that describes the working cycle of the device

High-Moment FeCo Magnetic Nanoparticles Obtained by Topochemical H-2 Reduction of Co-Ferrites

Featured Application Metallic nanoparticles with a high value of magnetization have potential interest for application in biomedicine, catalysis, composite permanent magnets, and other fields. Cobalt ferrite nanoparticles of different stoichiometries synthesized by a sol-gel autocombustion method were used as a starting material to obtain high-moment Fe50Co50 and Fe66Co34 metal nanoparticles by topochemical hydrogen reduction. Structural and magnetic investigations confirmed the formation of FeCo nanoparticles with crystallite sizes of about 30 nm and magnetization at 0.5 T of ~265 Am-2/kg (0 K), which was larger than the expected bulk value, likely because of the incorporation in the body-centered cubic (bcc) FeCo structure of the residual C atoms present on the surface of the oxide particles. Temperature-dependent magnetization measurements in the H-2 atmosphere were also performed to investigate in detail the reduction mechanism and the effect of an external magnetic field on the process efficiency

First Characterization of Novel Silicon Carbide Detectors with Ultra-High Dose Rate Electron Beams for FLASH Radiotherapy

Ultra-high dose rate (UHDR) beams for FLASH radiotherapy present significant dosimetric challenges. Although novel approaches for decreasing or correcting ion recombination in ionization chambers are being proposed, applicability of ionimetric dosimetry to UHDR beams is still under investigation. Solid-state sensors have been recently investigated as a valuable alternative for real-time measurements, especially for relative dosimetry and beam monitoring. Among them, Silicon Carbide (SiC) represents a very promising candidate, compromising between the maturity of Silicon and the robustness of diamond. Its features allow for large area sensors and high electric fields, required to avoid ion recombination in UHDR beams. In this study, we present simulations and experimental measurements with the low energy UHDR electron beams accelerated with the ElectronFLASH machine developed by the SIT Sordina company (IT). The response of a newly developed 1 × 1 cm2 SiC sensor in charge as a function of the dose-per-pulse and its radiation hardness up to a total delivered dose of 90 kGy, was investigated during a dedicated experimental campaign, which is, to our knowledge, the first characterization ever done of SiC with UHDR-pulsed beams accelerated by a dedicated ElectronFLASH LINAC. Results are encouraging and show a linear response of the SiC detector up to 2 Gy/pulse and a variation in the charge per pulse measured for a cumulative delivered dose of 90 kGy, within ±0.75%

LPS REMOVAL REDUCES CD80-MEDIATED ALBUMINURIA IN CRITICALLY ILL PATIENTS WITH GRAM-NEGATIVE SEPSIS

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomised to either have Coupled Plasma Filtration and Adsorption (CPFA) added to the standard care (n=35) or not (n=35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria and CD80 expression in Gram- sepsis, a swine model of LPS-induced AKI was set up. 3-hours after LPS infusion, animals were treated or not with CPFA for 6-hours. Treatment with CPFA significantly reduced serum cytokines, CRP, procalcitonin and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI