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1. Angiotensin II type 1 receptor mediates pulmonary hypertension and right ventricular remodeling induced by inhaled nicotine

   https://doi.org/10.1152/ajpheart.00883.2020  

   Fried, Nicholas D. ; Morris, Tamara M. ; Whitehead, Anna ; Lazartigues, Eric ; Yue, Xinping ; Gardner, Jason D. ( April 2021 , American Journal of Physiology-Heart and Circulatory Physiology)

   null (Ed.)

   Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective cohort of patients with PH is associated with improved survival. Here, we utilized losartan (an ARB specific for angiotensin II type 1 receptor) to further explore nicotine-induced PH. Male C57BL/6 mice received nicotine vapor for 12 h/day, and exposure was assessed using serum cotinine to achieve levels comparable to human smokers or electronic cigarette users. Mice were exposed to nicotine for 8 wk and a subset was treated with losartan via an osmotic minipump. Cardiac function was assessed using echocardiography and catheterization. Although nicotine exposure increased angiotensin II in the RV and lung, this finding was nonsignificant. Chronic, inhaled nicotine significantly increased RV systolic pressure and RV free wall thickness versus air control. These parameters were significantly lower in mice receiving both nicotine and losartan. Nicotine significantly increased RV internal diameter, with no differences seen between the nicotine and nicotine-losartan group. Neither nicotine nor losartan affected left ventricular structure or function. These findings provide the first evidence that antagonism of the angiotensin II type 1 receptor can ameliorate chronic, inhaled nicotine-induced PH and RV remodeling. NEW & NOTEWORTHY Chronic, inhaled nicotine causes pulmonary hypertension and right ventricular remodeling in mice. Treatment with losartan, an angiotensin II type 1 receptor antagonist, ameliorates nicotine-induced pulmonary hypertension and right ventricular remodeling. This novel finding provides preclinical evidence for the use of renin-angiotensin system-based therapies in the treatment of pulmonary hypertension, particularly in patients with a history of tobacco-product use. 

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2. The Puzzle of Spatial Sex Differences: Current Status and Prerequisites to Solutions

   https://doi.org/10.1111/cdep.12389  

   Newcombe, Nora S. ( October 2020 , Child Development Perspectives)

   In this review, I summarize what we know about the development of sex‐related differences in spatial skills, their potential malleability, and their possible causes. Current evidence suggests that sex differences increase in size with age, at least for skills with assessments suitable for use across development. However, male advantages vary from nonexistent to substantial, depending on the skills assessed, task parameters, and culture. Training and practice can improve spatial skills, although interventions tested so far do not eliminate the male advantage (when there is one). The complex pattern of increases with age, task variation, and cultural variation challenges efforts to theorize about causation. Progress requires identifying the underlying cognitive and neural structure of the spatial domain, developing reliable and valid assessment tools suitable for use across wide age ranges, gathering large datasets from a variety of cultural settings, and identifying and investigating specific mechanisms for growth and change.

    

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3. Sex differences in auditory brainstem response audiograms from vasopressin-deficient Brattleboro and wild-type Long-Evans rats

   https://doi.org/10.1371/journal.pone.0222096  

   Charlton, Payton E. ; Schatz, Kelcie C. ; Burke, Kali ; Paul, Matthew J. ; Dent, Micheal L. ; Delano, Paul Hinckley ( August 2019 , PLOS ONE)
4. Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload

   https://doi.org/10.3389/fphys.2022.948936  

   Odeigah, Oscar O. ; Valdez-Jasso, Daniela ; Wall, Samuel T. ; Sundnes, Joakim ( August 2022 , Frontiers in Physiology)

   Pulmonary arterial hypertension (PAH) is associated with substantial remodeling of the right ventricle (RV), which may at first be compensatory but at a later stage becomes detrimental to RV function and patient survival. Unlike the left ventricle (LV), the RV remains understudied, and with its thin-walled crescent shape, it is often modeled simply as an appendage of the LV. Furthermore, PAH diagnosis is challenging because it often leaves the LV and systemic circulation largely unaffected. Several treatment strategies such as atrial septostomy, right ventricular assist devices (RVADs) or RV resynchronization therapy have been shown to improve RV function and the quality of life in patients with PAH. However, evidence of their long-term efficacy is limited and lung transplantation is still the most effective and curative treatment option. As such, the clinical need for improved diagnosis and treatment of PAH drives a strong need for increased understanding of drivers and mechanisms of RV growth and remodeling (G&R), and more generally for targeted research into RV mechanics pathology. Computational models stand out as a valuable supplement to experimental research, offering detailed analysis of the drivers and consequences of G&R, as well as a virtual test bench for exploring and refining hypotheses of growth mechanisms. In this review we summarize the current efforts towards understanding RV G&R processes using computational approaches such as reduced-order models, three dimensional (3D) finite element (FE) models, and G&R models. In addition to an overview of the relevant literature of RV computational models, we discuss how the models have contributed to increased scientific understanding and to potential clinical treatment of PAH patients. 

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5. RVEX: Right Ventricular External Device for Biomimetic Support and Monitoring of the Right Heart

   https://doi.org/10.1002/admt.202101472  

   Pirozzi, Ileana ; Kight, Ali ; Shad, Rohan ; Han, Amy Kyungwon ; Dual, Seraina A. ; Fong, Robyn ; Jia, Allison ; Hiesinger, William ; Yock, Paul ; Cutkosky, Mark ( February 2022 , Advanced Materials Technologies)

   Right ventricular (RV) failure remains a significant burden for patients with advanced heart failure, especially after major cardiac surgeries such as implantation of left ventricular assist devices. Device solutions that can assist the complex biological function of heart muscle without the disadvantages of bulky designs and infection‐prone drivelines remain an area of pressing clinical need, especially for the right ventricle. In addition, devices that incur contact between blood and artificial surfaces mandate long‐term use of blood‐thinning medications, carrying increased risks for the patients. This work describes the design of a biomimetic, elastic sleeve to support RV‐specific motion via tuned regional mechanical properties. The RV external device (RVEX) in computational models as well as benchtop models and ex vivo (i.e., explanted heart) setups are evaluated to characterize the device and predict functional benefit. Additionally, long‐term implantation potential is demonstrated in mice. Finally, the ability to sensorize the RVEX device to yield resistive self‐sensing capabilities to continuously monitor ventricular deformation, as demonstrated in benchtop experiments and in live animal surgeries, is proposed.

    

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