Factors in Homo and Heterotypic Aggregate Formation in Sepsis

Sepsis, a severe systemic inflammatory response to an infection that can be bacterial, viral or fungal in origin, remains a serious condition with high mortality. The dynamics in the immune response (immune activation, over activation and exhaustion) during development and progression of sepsis pose a problem in the design of new treatment approaches. This review focuses on the understanding of molecular interactions that lead to the formation of cellular aggregates in sepsis and puts novel treatment targets in the context of these interactions

Gain flattened S+C+L-band bidirectional thulium doped fiber/multi-section fiber optical parametric hybrid amplifier

This article demonstrates the achievement of optical amplification across the S, C, and L-bands. A hybrid amplifier is proposed that utilizes a combination of bidirectional thulium-doped fiber amplifier (TDFA) and multi-section fiber optical parametric amplifier. With careful selection of TDFA and parametric amplifier parameters, gain can be achieved over complementary bandwidth regions. Resultantly, better gain flatness is achieved over the whole effective bandwidth of 170 nm. The amplifier being proposed is evaluated for a system consisting of 18 wavelength division multiplexed channels, each with a capacity of 100 Gb/s, and a channel spacing of 10 nm. By setting the input power per channel to an optimal value of –30 dBm, the parameters are adjusted to attain a flat gain exceeding 23.52 dB, accompanied by a gain ripple of only 2.09 dB. These parameters are optimized over a wavelength range between 1460 nm and 1630 nm.Other Information Published in: Ain Shams Engineering Journal License: http://creativecommons.org/licenses/by-nc-nd/4.0/See article on publisher's website: https://dx.doi.org/10.1016/j.asej.2023.102497</p

Glycated albumin modulates the contact system with implications for the kallikrein-kinin and intrinsic coagulation systems

Background: Human serum albumin (HSA) is the most abundant plasma protein and is sensitive to glycation in vivo. The chronic hyperglycemic conditions in patients with diabetes mellitus (DM) induce a nonenzymatic Maillard reaction that denatures plasma proteins and forms advanced glycation end products (AGEs). HSA-AGE is a prevalent misfolded protein in patients with DM and is associated with factor XII activation and downstream proinflammatory kallikrein-kinin system activity without any associated procoagulant activity of the intrinsic pathway. Objectives: This study aimed to determine the relevance of HSA-AGE toward diabetic pathophysiology. Methods: The plasma obtained from patients with DM and euglycemic volunteers was probed for activation of FXII, prekallikrein (PK), and cleaved high-molecular-weight kininogen by immunoblotting. Constitutive plasma kallikrein activity was determined via chromogenic assay. Activation and kinetic modulation of FXII, PK, FXI, FIX, and FX via in vitro-generated HSA-AGE were explored using chromogenic assays, plasma-clotting assays, and an in vitro flow model using whole blood. Results: Plasma obtained from patients with DM contained increased plasma AGEs, activated FXIIa, and resultant cleaved cleaved high-molecular-weight kininogen. Elevated constitutive plasma kallikrein enzymatic activity was identified, which positively correlated with glycated hemoglobin levels, representing the first evidence of this phenomenon. HSA-AGE, generated in vitro, triggered FXIIa-dependent PK activation but limited the intrinsic coagulation pathway activation by inhibiting FXIa and FIXa-dependent FX activation in plasma. Conclusion: These data indicate a proinflammatory role of HSA-AGEs in the pathophysiology of DM via FXII and kallikrein-kinin system activation. A procoagulant effect of FXII activation was lost through the inhibition of FXIa and FIXa-dependent FX activation by HSA-AGEs.</p