Progress in solving the sex hormone paradox in pulmonary hypertension

2014 ◽  
Vol 307 (1) ◽  
pp. L7-L26 ◽  
Author(s):  
Tim Lahm ◽  
Rubin M. Tuder ◽  
Irina Petrache
Keyword(s):  
Animal Models ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Future Research ◽  
Estrogen Metabolism ◽  
Hormone Synthesis ◽  
17Β Estradiol ◽  
Pulmonary Arterial ◽  
And Gender ◽  
Underlying Mechanisms

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with marked morbidity and mortality. Even though being female represents one of the most powerful risk factors for PAH, multiple questions about the underlying mechanisms remain, and two “estrogen paradoxes” in PAH exist. First, it is puzzling why estrogens have been found to be protective in various animal models of PAH, whereas PAH registries uniformly demonstrate a female susceptibility to the disease. Second, despite the pronounced tendency for the disease to develop in women, female PAH patients exhibit better survival than men. Recent mechanistic studies in classical and in novel animal models of PAH, as well as recent studies in PAH patients, have significantly advanced the field. In particular, it is now accepted that estrogen metabolism and receptor signaling, as well as estrogen interactions with key pathways in PAH development, appear to be potent disease modifiers. A better understanding of these interactions may lead to novel PAH therapies. It is the purpose of this review to 1) review sex hormone synthesis, metabolism, and receptor physiology; 2) assess the context in which sex hormones affect PAH pathogenesis; 3) provide a potential explanation for the observed estrogen paradoxes and gender differences in PAH; and 4) identify knowledge gaps and future research opportunities. Because the majority of published studies investigated 17β-estradiol and/or its metabolites, this review will primarily focus on pulmonary vascular and right ventricular effects of estrogens. Data for other sex hormones will be discussed very briefly.

scholarly journals Current Understanding of the Right Ventricle Structure and Function in Pulmonary Arterial Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Danial Sharifi Kia ◽  
Kang Kim ◽  
Marc A. Simon
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Structure And Function ◽  
Biomechanical Analysis ◽  
Current Understanding ◽  
Future Research ◽  
Close Link ◽  
Pulmonary Arterial ◽  
Underlying Mechanisms ◽  
And Function

Pulmonary arterial hypertension (PAH) is a disease resulting in increased right ventricular (RV) afterload and RV remodeling. PAH results in altered RV structure and function at different scales from organ-level hemodynamics to tissue-level biomechanical properties, fiber-level architecture, and cardiomyocyte-level contractility. Biomechanical analysis of RV pathophysiology has drawn significant attention over the past years and recent work has found a close link between RV biomechanics and physiological function. Building upon previously developed techniques, biomechanical studies have employed multi-scale analysis frameworks to investigate the underlying mechanisms of RV remodeling in PAH and effects of potential therapeutic interventions on these mechanisms. In this review, we discuss the current understanding of RV structure and function in PAH, highlighting the findings from recent studies on the biomechanics of RV remodeling at organ, tissue, fiber, and cellular levels. Recent progress in understanding the underlying mechanisms of RV remodeling in PAH, and effects of potential therapeutics, will be highlighted from a biomechanical perspective. The clinical relevance of RV biomechanics in PAH will be discussed, followed by addressing the current knowledge gaps and providing suggested directions for future research.

scholarly journals Gait Variability and Multiple Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Michael J. Socie ◽  
Jacob J. Sosnoff
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Importance ◽  
Gait Variability ◽  
Adverse Outcomes ◽  
Assistive Device ◽  
Future Research ◽  
And Gender ◽  
Underlying Mechanisms ◽  
Device Use ◽  
Disability Level

Gait variability, that is, fluctuations in movement during walking, is an indicator of walking function and has been associated with various adverse outcomes such as falls. In this paper, current research concerning gait variability in persons with multiple sclerosis (MS) is discussed. It is well established that persons with MS have greater gait variability compared to age and gender matched controls without MS. The reasons for the increase in gait variability are not completely understood. Evidence indicates that disability level, assistive device use, attentional requirement, and fatigue are related to gait variability in persons with MS. Future research should address the time-evolving structure (i.e., temporal characteristics) of gait variability, the clinical importance of gait variability, and underlying mechanisms that drive gait variability in individuals with MS.

scholarly journals Sex Hormone Regulation of Proteins Modulating Mitochondrial Metabolism, Dynamics and Inter-Organellar Cross Talk in Cardiovascular Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Shannon Lynch ◽  
James E. Boyett ◽  
M. Ryan Smith ◽  
Samantha Giordano-Mooga
Keyword(s):  
Cardiovascular Disease ◽  
Sex Hormones ◽  
Mitochondrial Biogenesis ◽  
Cross Talk ◽  
Mitochondrial Dynamics ◽  
Sex Hormone ◽  
Regulatory Role ◽  
Future Research ◽  
Hormone Regulation

Cardiovascular disease (CVD) is the leading cause of death in the U.S. and worldwide. Sex-related disparities have been identified in the presentation and incidence rate of CVD. Mitochondrial dysfunction plays a role in both the etiology and pathology of CVD. Recent work has suggested that the sex hormones play a role in regulating mitochondrial dynamics, metabolism, and cross talk with other organelles. Specifically, the female sex hormone, estrogen, has both a direct and an indirect role in regulating mitochondrial biogenesis via PGC-1α, dynamics through Opa1, Mfn1, Mfn2, and Drp1, as well as metabolism and redox signaling through the antioxidant response element. Furthermore, data suggests that testosterone is cardioprotective in males and may regulate mitochondrial biogenesis through PGC-1α and dynamics via Mfn1 and Drp1. These cell-signaling hubs are essential in maintaining mitochondrial integrity and cell viability, ultimately impacting CVD survival. PGC-1α also plays a crucial role in inter-organellar cross talk between the mitochondria and other organelles such as the peroxisome. This inter-organellar signaling is an avenue for ameliorating rampant ROS produced by dysregulated mitochondria and for regulating intrinsic apoptosis by modulating intracellular Ca2+ levels through interactions with the endoplasmic reticulum. There is a need for future research on the regulatory role of the sex hormones, particularly testosterone, and their cardioprotective effects. This review hopes to highlight the regulatory role of sex hormones on mitochondrial signaling and their function in the underlying disparities between men and women in CVD.

scholarly journals From Denial of Facts to Rationalization and Avoidance: Ideology, Needs, and Gender Predict the Spectrum of Climate Denial and Self-Protection

2021 ◽  
Author(s):  
Marlis Wullenkord
Keyword(s):  
Structural Equation ◽  
Latent Profile Analysis ◽  
Profile Analysis ◽  
Need Satisfaction ◽  
Future Research ◽  
Right Wing ◽  
Outcome Severity ◽  
And Gender ◽  
Underlying Mechanisms ◽  
Self Protection

Denying climate change can take many forms, ranging on a spectrum from outright denial of facts (literal denial), over re-interpretation or distortion of facts (interpretive denial, e.g., denial of personal and global outcome severity), to the acknowledgement of facts but denial of their implications (implicatory denial, e.g., avoidance, denial of guilt, rationalization of own involvement). This study aimed at 1) exploring potential distinct profiles within the spectrum of climate denial and self-protection and 2) investigating relations with right-wing ideological conviction and gender (established predictors) but also need satisfaction and value orientation. Analysis of a German quota sample (N=1007) revealed the following: Participants differed in the extent to which they endorsed all types of climate-denial and self-protection but there were no distinct profiles of climate denial and self-protection in the data, according to latent profile analysis. As pre-registered, structural equation modelling revealed that people who reported right-wing ideological convictions reported more climate denial and self-protection along the spectrum of denial but especially literal and interpretive denial. Absence of need satisfaction and male gender were significant additional but weaker predictors of implicatory denial. Future research should employ longitudinal, experimental, mixed-methods designs to further disentangle the underlying mechanisms and functionality of climate denial.

scholarly journals Sex Differences, Estrogen Metabolism and Signaling in the Development of Pulmonary Arterial Hypertension

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanan Sun ◽  
Shreya Sangam ◽  
Qiang Guo ◽  
Jian Wang ◽  
Haiyang Tang ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Animal Models ◽  
Arterial Hypertension ◽  
Heart Function ◽  
Female Rats ◽  
Estrogen Signaling ◽  
Estrogen Metabolism ◽  
Right Heart ◽  
Right Heart Function ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a complex and devastating disease with a poor long-term prognosis. While women are at increased risk for developing PAH, they exhibit superior right heart function and higher survival rates than men. Susceptibility to disease risk in PAH has been attributed, in part, to estrogen signaling. In contrast to potential pathological influences of estrogen in patients, studies of animal models reveal estrogen demonstrates protective effects in PAH. Consistent with this latter observation, an ovariectomy in female rats appears to aggravate the condition. This discrepancy between observations from patients and animal models is often called the “estrogen paradox.” Further, the tissue-specific interactions between estrogen, its metabolites and receptors in PAH and right heart function remain complex; nonetheless, these relationships are essential to characterize to better understand PAH pathophysiology and to potentially develop novel therapeutic and curative targets. In this review, we explore estrogen-mediated mechanisms that may further explain this paradox by summarizing published literature related to: (1) the synthesis and catabolism of estrogen; (2) activity and functions of the various estrogen receptors; (3) the multiple modalities of estrogen signaling in cells; and (4) the role of estrogen and its diverse metabolites on the susceptibility to, and progression of, PAH as well as their impact on right heart function.

scholarly journals The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

2020 ◽  
Vol 22 (1) ◽  
pp. 11
Author(s):  
Erzsébet Kövesdi ◽  
Edina Szabó-Meleg ◽  
István M. Abrahám
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Animal Studies ◽  
Treatment Options ◽  
Endocrine System ◽  
Sex And Gender ◽  
17Β Estradiol ◽  
And Gender

Patients surviving traumatic brain injury (TBI) face numerous neurological and neuropsychological problems significantly affecting their quality of life. Extensive studies over the past decades have investigated pharmacological treatment options in different animal models, targeting various pathological consequences of TBI. Sex and gender are known to influence the outcome of TBI in animal models and in patients, respectively. Apart from its well-known effects on reproduction, 17β-estradiol (E2) has a neuroprotective role in brain injury. Hence, in this review, we focus on the effect of E2 in TBI in humans and animals. First, we discuss the clinical classification and pathomechanism of TBI, the research in animal models, and the neuroprotective role of E2. Based on the results of animal studies and clinical trials, we discuss possible E2 targets from early to late events in the pathomechanism of TBI, including neuroinflammation and possible disturbances of the endocrine system. Finally, the potential relevance of selective estrogenic compounds in the treatment of TBI will be discussed.

scholarly journals Sex Differences in Right Ventricular Dysfunction: Insights From the Bench to Bedside

2021 ◽  
Vol 11 ◽  
Author(s):  
Jennifer Keen ◽  
Sasha Z. Prisco ◽  
Kurt W. Prins
Keyword(s):  
Sex Differences ◽  
Right Ventricular ◽  
Sex Hormones ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Unmet Need ◽  
Right Ventricular Dysfunction ◽  
Sex Hormone ◽  
Life Threatening ◽  
Pulmonary Arterial ◽  
Rv Function

There are inherent distinctions in right ventricular (RV) performance based on sex as females have better RV function than males. These differences are magnified and have very important prognostic implications in two RV-centric diseases, pulmonary hypertension (PH), and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). In both PH and ARVC/D, RV dysfunction results in poor patient outcomes. However, there are no currently approved therapies specifically targeting the failing RV, an important unmet need for these two life-threatening disorders. In this review, we highlight human data demonstrating divergent RV phenotypes in healthy, PH, and ARVC/D patients based on sex. Furthermore, we discuss the links between estrogen (the female predominant sex hormone), testosterone (the male predominant sex hormone), and dehydroepiandrosterone (a precursor hormone for multiple sex hormones in males and females) and RV function in both disorders. To provide potential mechanistic insights into sex differences in RV function, we review data that investigate how sex hormones combat or contribute to pathophysiological changes in the RV. Finally, we highlight the ongoing clinical trials in pulmonary arterial hypertension targeting estrogen and dehydroepiandrosterone signaling. Hopefully, a greater understanding of the factors that promote superior RV function in females will lead to novel therapeutic approaches to combat RV dysfunction in PH and ARVC/D.

Self-Compassion and Quality of Life in Adults Who Stutter

2020 ◽  
Vol 29 (4) ◽  
pp. 2097-2108
Author(s):  
Robyn L. Croft ◽  
Courtney T. Byrd
Keyword(s):  
Quality Of Life ◽  
Social Connectedness ◽  
The Self ◽  
Future Research ◽  
Self Compassion ◽  
Adults Who Stutter ◽  
And Gender ◽  
Relationship Of ◽  
The Impact

Purpose The purpose of this study was to identify levels of self-compassion in adults who do and do not stutter and to determine whether self-compassion predicts the impact of stuttering on quality of life in adults who stutter. Method Participants included 140 adults who do and do not stutter matched for age and gender. All participants completed the Self-Compassion Scale. Adults who stutter also completed the Overall Assessment of the Speaker's Experience of Stuttering. Data were analyzed for self-compassion differences between and within adults who do and do not stutter and to predict self-compassion on quality of life in adults who stutter. Results Adults who do and do not stutter exhibited no significant differences in total self-compassion, regardless of participant gender. A simple linear regression of the total self-compassion score and total Overall Assessment of the Speaker's Experience of Stuttering score showed a significant, negative linear relationship of self-compassion predicting the impact of stuttering on quality of life. Conclusions Data suggest that higher levels of self-kindness, mindfulness, and social connectedness (i.e., self-compassion) are related to reduced negative reactions to stuttering, an increased participation in daily communication situations, and an improved overall quality of life. Future research should replicate current findings and identify moderators of the self-compassion–quality of life relationship.

The use of ICT by SMMEs in a Digital Economy: A case study in Buffalo City Metropolitan in South Africa [Abstract]

10.28945/4314 ◽  
2019 ◽  
Keyword(s):  
South Africa ◽  
Technology Acceptance ◽  
21St Century ◽  
Common Knowledge ◽  
Digital Economy ◽  
Future Research ◽  
Wealth Creation ◽  
Underdeveloped Areas ◽  
And Gender ◽  
Set Up

Aim/Purpose: The goal of this study is to advance understanding of ICT utilization by SMMEs by checking access, ability (in terms of technological skills) and usage of ICT among some SMMEs entrepreneurs operating their businesses in an underdeveloped areas to enhance their business activities in order to utilizes the digital opportunities 21st century digital economies present. Background: In today’s world no nation or region is untouched by the forces of globalization and digital economy. One of the key pioneering forces of globalization is the advances of ICT like internet, social networks, etc. In the sphere of business, this pioneering force has also altered the way businesses and organizations communicate and interact with customers and society at large. Such alternation presents obvious opportunities for wealth creation and growth for businesses and organizations that are well-equipped to take advantages of them. But for those that are less-equipped, particularly SMMEs, globalization can easily lead to fore-closures and marginalization. It is a common knowledge that SMMEs entrepreneurs mostly rely on ICT gadgets like mobile phone, Laptops, Tablets to conduct their business activities as many of them don’t have enough capital to set up offices with necessary equipment. Therefore, using various ICT functions/programs on these ICT devices to enhance their business activities are critical to their businesses in the 21st century digital economies. Methodology: Purposeful sampling was used to approach fifty-four SMMEs entrepreneurs operating their businesses in underdeveloped areas locally called Townships in Buffalo City Metropolitan. Microsoft excel was used in the descriptive statistics. Contribution: This research will add to the growing knowledge ICT usage in SMMEs in the 21st century digital economies. Findings: The results indicate that the participating SMMEs entrepreneurs need to be educated, trained and supported in the use of the ICT applicable to enhance their business activities in order for them to take advantages of 21st century digital economies present. Recommendations for Practitioners: The agencies tasked with looking after SMMEs in South Africa needs to consider the lacked of utilisation of ICTs by SMMEs entrepreneurs operating their businesses in underdeveloped areas as one of the barrier to growing of their businesses and take necessary steps to address it. Recommendation for Researchers: Since age and gender have been proven to be key-moderating variables in many technology acceptance models. There is a need to explore in depth whether the factors of gender and age also act as barriers. Impact on Society: The research will assist stakeholders, policy makers and agencies tasked with looking after SMMEs to identify the barriers hindering SMMEs to grow and address them accordingly. Future Research: More work needs to be done to check whether gender, age of the SMMEs entrepreneurs have some effects on their attitude towards the integration of ICT into their business activities.

Feeling Threatened by Immigrants: The Role of Ideology and Subjective Societal Status

2020 ◽  
Author(s):  
Michael Bollwerk ◽  
Bernd Schlipphak ◽  
Joscha Stecker ◽  
Jens Hellmann ◽  
Gerald Echterhoff ◽  
...  
Keyword(s):  
Online Survey ◽  
Middle Eastern ◽  
Social Dominance Orientation ◽  
Survey Study ◽  
Future Research ◽  
Right Wing Authoritarianism ◽  
Threat Perceptions ◽  
Contextual Determinants ◽  
Intergroup Conflicts ◽  
And Gender

Threat perceptions towards immigrants continue to gain importance in the context of growing international migration. To reduce associated intergroup conflicts, it is crucial to understand the personal and contextual determinants of perceived threat. In a large online survey study (N = 1,184), we investigated the effects of ideology (i.e., Right-Wing Authoritarianism and Social Dominance Orientation), subjective societal status (SSS) and their interaction effects in predicting symbolic and realistic threat perceptions towards Middle Eastern immigrants. Results showed that ideology (higher RWA and SDO) and lower SSS significantly predicted both symbolic and realistic threat, even after controlling for income, education, age, and gender. Furthermore, ideology and SSS interacted significantly in predicting realistic threat, with higher levels of SDO and RWA enhancing the effect of SSS. In the discussion, we focus on the implications of our findings with respect to understanding societal conflicts, discuss methodological limitations, and provide directions for future research.

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