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Background: Left ventricular stroke work index (LVSWI) and afterload‐related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle‐tracking echocardiography parameter, Pressure‐Strain Product (PSP), can non‐invasively predict catheter‐based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub‐phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis‐like conditions. Methods: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis‐like (n = 8) or (2) non‐sepsis‐like (n = 8) group. Each ARDS and sepsis‐like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter‐based LVSWI (the product of stroke work index, mean arterial pressure and.0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). Results: PSPcirc showed a significant correlation with LVSWI (r2 =.66, p <.001) and ACP (r2 =.82, p <.001) in the sepsis‐like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC.86) and ACP (AUC.88), and PSPrad predicted serum lactate (AUC.75) better than LV ejection fraction, global circumferential and radial strain. Conclusions: A novel PSP has the potential to non‐invasively predict catheter‐based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Thyroid follicles, the functional units of the thyroid gland, are delineated by a monolayer of thyrocytes resting on a continuous basement membrane. The developmental mechanisms of folliculogenesis, whereby follicles are formed by the reorganization of a non-structured mass of non-polarized epithelial cells, are largely unknown. Here we show that assembly of the epithelial basement membrane is crucial for folliculogenesis and is controlled by endothelial cell invasion and by BMP-Smad signaling in thyrocytes. Thyroid-specific Smad1 and Smad5 double-knockout (Smad1/5dKO) mice displayed growth retardation, hypothyroidism and defective follicular architecture. In Smad1/5dKO embryonic thyroids, epithelial cells remained associated in large clusters and formed small follicles. Although similar follicular defects are found in Vegfa knockout (VegfaKO) thyroids, Smad1/5dKO thyroids had normal endothelial cell density yet impaired endothelial differentiation. Interestingly, both VegfaKO and Smad1/5dKO thyroids displayed impaired basement membrane assembly. Furthermore, conditioned medium (CM) from embryonic endothelial progenitor cells (eEPCs) rescued the folliculogenesis defects of both Smad1/5dKO and VegfaKO thyroids. Laminin α1, β1 and γ1, abundantly released by eEPCs into CM, were crucial for folliculogenesis. Thus, epithelial Smad signaling and endothelial cell invasion promote folliculogenesis via assembly of the basement membrane. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non‐invasively measuring these parameters during veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure‐Strain Product (PSP), a novel speckle‐tracking echocardiography parameter, (1) can correlate with pressure‐volume catheter‐based LVSWI and CPI, and (2) can be load‐independent during the flow modification of V‐A ECMO.Nine Dorset‐cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V‐A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24‐h observation, echocardiographic parameters as well as pressure‐volume catheter‐based LVSWI and CPI were simultaneously measured with X and following X‐1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively.PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure‐volume catheter‐based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558).A novel echocardiographic parameter, PSP, may non‐invasively predict pressure‐volume catheter‐based LVSWI and CPI in a load‐independent manner in a cardiogenic shock supported by V‐A ECMO. [ABSTRACT FROM AUTHOR]