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Background: Prior studies have established the impact of sex differences on pulmonary arterial hypertension (PAH). However, it remains unclear whether these sex differences extend to other hemodynamic subtypes of pulmonary hypertension (PH). Methods: We examined sex differences in PH and hemodynamic PH subtypes in a hospital-based cohort of individuals who underwent right heart catheterization between 2005-2016. We utilized multivariable linear regression to assess the association of sex with hemodynamic indices of RV function [PA pulsatility index (PAPi), RV stroke work index (RVSWI), and right atrial: pulmonary capillary wedge pressure ratio (RA:PCWP)]. We then used Cox regression models to examine the association between sex and clinical outcomes among those with PH. Results: Among 5208 individuals with PH (mean age 64 years, 39% women), there was no significant sex difference in prevalence of PH overall. However, when stratified by PH subtype, 31% of women vs 22% of men had pre-capillary (P<0.001), 39% vs 51% had post-capillary (P=0.03), and 30% vs 27% had mixed PH (P=0.08). Female sex was associated with better RV function by hemodynamic indices, including higher PAPi and RVSWI, and lower RA:PCWP ratio (P<0.001 for all). Over 7.3 years of follow-up, female sex was associated with a lower risk of heart failure hospitalization (HR 0.83, CI 95% CI 0.74- 0.91, p value <0.001). Conclusions: Across a broad hospital-based sample, more women had pre-capillary and more men had post-capillary PH. Compared with men, women with PH had better hemodynamic indices of RV function and a lower risk of HF hospitalization. CLINICAL PERSPECTIVE: What Is New? Although sex differences have been explored in pulmonary arterial hypertension, sex differences across pulmonary hypertension (PH) in broader samples inclusive of all hemodynamic subtypes remain less well definedWe delineate sex differences in hemodynamic subtypes of PH and associated right ventricular function in a large, heterogenous, hospital-based sample of individuals who underwent right heart catheterizationSex has a significant impact on prevalence of PH across hemodynamic subtypes as well as associated RV function What Are the Clinical Implications? Understanding sex differences across different PH hemodynamic subtypes is paramount to refining risk stratification between men and womenFurther elucidating sex differences in associated RV function and clinical outcomes may aid in developing sex-specific therapies or management strategies to improve clinical outcomes.
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Directional cell migration is a crucial step in wound healing, influenced by electrical and topographic stimulations. However, the underlying mechanism and the combined effects of these two factors on cell migration remain unclear. This study explores cell migration under various combinations of guided straight line (SL) spacing, conductivity, and the relative direction of electric field (EF) and SL. Electrowriting is employed to fabricate conductive (multiwalled carbon nanotube/polycaprolactone (PCL)) and nonconductive (PCL) SL, with narrow (50 µm) and wide (400 µm) spacing that controls the topographic stimulation strength. Results show that various combinations of electrical and topographic stimulation yield significantly distinct effects on cell migration direction and speed; cells migrate fastest with the most directivity in the case of conductive, narrow-spacing SL parallel to EF. A physical model based on intercellular interactions is developed to capture the underlying mechanism of cell migration under SL and EF stimulations, in agreement with experimental observations. In vivo skin wound healing assay further confirmed that the combination of EF (1 V cm-1) and parallelly aligned conductive fibers accelerated the wound healing process. This study presents a promising approach to direct cell migration and enhance wound healing by optimizing synergistic electrical and topographic stimulations.
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Multimaterial integration, such as soft elastic and stiff components, exhibits rich deformation and functional behaviors to meet complex needs. Integrating multimaterials in the level of individual fiber is poised to maximize the functional design capacity of smart wearable electronic textiles, but remains unfulfilled. Here, this work continuously integrates stiff and soft elastic components into single fiber to fabricate encoded mechano-metafiber by programmable microfluidic sequence spinning (MSS). The sequences with programmable modulus feature the controllable localization of strain along metafiber length. The mechano-metafibers feature two essential nonlinear deformation modes, which are local strain amplification and retardation. This work extends the sequence-encoded metafiber into fiber networks to exhibit greatly enhanced strain amplification and retardation capability in cascades. Local strain engineering enables the design of highly sensitive strain sensors, stretchable fiber devices to protect brittle components and the fabrication of high-voltage supercapacitors as well as axial electroluminescent arrays. The approach allows the scalably design of multimaterial metafibers with programmable localized mechanical properties for woven metamaterials, smart textiles, and wearable electronics.
