Sex and the G Protein-Coupled Estrogen Receptor Impact Vascular Stiffness.

[Figure: see text].

Parental active tracking measures and health behaviors during high school and college.

Objective: This study developed and tested new measures of youth perceptions of parental active efforts to track their activities during adolescence and college. Participants and Methods: Between March and October 2016, a sample of 314 college students aged 18-25 completed a survey including their perceptions of their parent's active tracking efforts during high school and college. Items were then analyzed, and internally consistent measures were derived. Results: The new measures demonstrated significant convergent validity with the three sources of parental knowledge constructs (parental solicitation, parental control, and youth disclosure). Greater perceived parental active tracking efforts during adolescence and in college were associated with better health behaviors in both time periods. Conclusions: The newly derived measures represent appropriate and predictive indices of parental tracking behaviors during adolescence and college, designed specifically with these populations in mind, to be used in pre-intervention and intervention work with parents.

Profiles of family routines during adolescence associated with profiles of health behaviors in young adulthood.

This study examined associations between profiles of family routines in early adolescence and profiles of health behaviors during young adulthood. In a sample of 4565 individuals, latent transition analysis indicated individuals in a family characterized by low involvement in adolescence were most likely, across classes, to demonstrate a profile characterized by substance use in young adulthood. The high-involvement class during adolescence was least likely to be a substance user but was relatively likely to be in the poor diet and exercise class during young adulthood. Results highlight the utility of examining complex family influences on health using person-centered methods.

G Protein-Coupled Estrogen Receptor Protects From Angiotensin II-Induced Increases in Pulse Pressure and Oxidative Stress.

Our previous work showed that the G protein-coupled estrogen receptor (GPER) is protective in the vasculature and kidneys during angiotensin (Ang) II-dependent hypertension by inhibiting oxidative stress. The goal of the current study was to assess the impact of GPER deletion on sex differences in Ang II-induced hypertension and oxidative stress. Male and female wildtype and GPER knockout mice were implanted with radiotelemetry probes for measurement of baseline blood pressure before infusion of Ang II (700 ng/kg/min) for 2 weeks. Mean arterial pressure was increased to the same extent in all groups, but female wildtype mice were protected from Ang II-induced increases in pulse pressure, aortic wall thickness, and Nox4 mRNA. In vitro studies using vascular smooth muscle cells found that pre-treatment with the GPER agonist G-1 inhibited Ang II-induced ROS and NADP/NADPH. Ang II increased while G-1 decreased Nox4 mRNA and protein. The effects of Ang II were blocked by losartan and Nox4 siRNA, while the effects of G-1 were inhibited by adenylyl cyclase inhibition and mimicked by phosphodiesterase inhibition. We conclude that during conditions of elevated Ang II, GPER via the cAMP pathway suppresses Nox4 transcription to limit ROS production and prevent arterial stiffening. Taken together with our previous work, this study provides insight into how acute estrogen signaling via GPER provides cardiovascular protection during Ang II hypertension and potentially other diseases characterized by increased oxidative stress.

Biaxial Basal Tone and Passive Testing of the Murine Reproductive System Using a Pressure Myograph.

The female reproductive organs, specifically the vagina and cervix, are composed of various cellular components and a unique extracellular matrix (ECM). Smooth muscle cells exhibit a contractile function within the vaginal and cervical walls. Depending on the biochemical environment and the mechanical distension of the organ walls, the smooth muscle cells alter the contractile conditions. The contribution of the smooth muscle cells under baseline physiological conditions is classified as a basal tone. More specifically, a basal tone is the baseline partial constriction of smooth muscle cells in the absence of hormonal and neural stimulation. Furthermore, the ECM provides structural support for the organ walls and functions as a reservoir for biochemical cues. These biochemical cues are vital to various organ functions, such as inciting growth and maintaining homeostasis. The ECM of each organ is composed primarily of collagen fibers (mostly collagen types I, III, and V), elastic fibers, and glycosaminoglycans/proteoglycans. The composition and organization of the ECM dictate the mechanical properties of each organ. A change in ECM composition may lead to the development of reproductive pathologies, such as pelvic organ prolapse or premature cervical remodeling. Furthermore, changes in ECM microstructure and stiffness may alter smooth muscle cell activity and phenotype, thus resulting in the loss of the contractile force. In this work, the reported protocols are used to assess the basal tone and passive mechanical properties of the nonpregnant murine vagina and cervix at 4-6 months of age in estrus. The organs were mounted in a commercially available pressure myograph and both pressure-diameter and force-length tests were performed. Sample data and data analysis techniques for the mechanical characterization of the reproductive organs are included. Such information may be useful for constructing mathematical models and rationally designing therapeutic interventions for women's health pathologies.

Smooth muscle regional contribution to vaginal wall function.

Pelvic organ prolapse is characterized as the descent of the pelvic organs into the vaginal canal. In the USA, there is a 12% lifetime risk for requiring surgical intervention. Although vaginal childbirth is a well-established risk factor for prolapse, the underlying mechanisms are not fully understood. Decreased smooth muscle organization, composition and maximum muscle tone are characteristics of prolapsed vaginal tissue. Maximum muscle tone of the vaginal wall was previously investigated in the circumferential or axial direction under uniaxial loading; however, the vaginal wall is subjected to multiaxial loads. Further, the contribution of vaginal smooth muscle basal (resting) tone to mechanical function remains undetermined. The objectives of this study were to determine the contribution of smooth muscle basal and maximum tone to the regional biaxial mechanical behaviour of the murine vagina. Vaginal tissue from C57BL/6 mice was subjected to extension-inflation protocols (n = 10) with and without basal smooth muscle tone. Maximum tone was induced with KCl under various circumferential (n = 5) and axial (n = 5) loading conditions. The microstructure was visualized with multiphoton microscopy (n = 1), multiaxial histology (n = 4) and multiaxial immunohistochemistry (n = 4). Smooth muscle basal tone decreased material stiffness and increased anisotropy. In addition, maximum vaginal tone was decreased with increasing intraluminal pressures. This study demonstrated that vaginal muscle tone contributed to the biaxial mechanical response of murine vaginal tissue. This may be important in further elucidating the underlying mechanisms of prolapse, in order to improve current preventative and treatment strategies.

Evaluating residual strain throughout the murine female reproductive system.

Mounting evidence suggests that cells within soft tissues seek to maintain a preferred biomechanical state. Residual stress is defined as the stress that remains in a tissue when all external loads are removed and contributes to tissue mechanohomeostasis by decreasing the transmural gradient of wall stress. Current computational models of pelvic floor mechanics, however, often do not consider residual stress. Residual strain, a result of residual stress can be quantitatively measured through opening angle experiments. Therefore, the objective of this study is to quantify the regional variations in opening angles along the murine female reproductive system at estrus and diestrus, to quantify residual strain in the maintenance state of sexually mature females. Further, evidence suggests that hydrophilic glycosaminoglycan/proteoglycans are integral to cervical remodeling. Thus, variations in opening angles following hypo-osmotic loading are evaluated. Opening angle experiments were performed along the murine reproductive system in estrus (n = 8) and diestrus (n = 8) and placed in hypo-osmotic solution. Measurements of thickness and volume were also obtained for each group. Differences (p < 0.05) in opening angle were observed with respect to region and loading, however, differences with respect to estrous stage were not significant. Thickness values were significant (p < 0.05) with respect to region only. The effects of both estrous cycle and region resulted in significant differences (p < 0.05) in observed volume. The observed regional differences indicate variation in the stress-free state among the reproductive system which may have implications for future computational models to advance women's reproductive health.

New insights into arterial stiffening: does sex matter?

This review discusses sexual dimorphism in arterial stiffening, disease pathology interactions, and the influence of sex on mechanisms and pathways. Arterial stiffness predicts cardiovascular mortality independent of blood pressure. Patients with increased arterial stiffness have a 48% higher risk for developing cardiovascular disease. Like other cardiovascular pathologies, arterial stiffness is sexually dimorphic. Young women have lower stiffness than aged-matched men, but this sex difference reverses during normal aging. Estrogen therapy does not attenuate progressive stiffening in postmenopausal women, indicating that currently prescribed drugs do not confer protection. Although remodeling of large arteries is a protective adaptation to higher wall stress, arterial stiffening increases afterload to the left ventricle and transmits higher pulsatile pressure to smaller arteries and target organs. Moreover, an increase in aortic stiffness may precede or exacerbate hypertension, particularly during aging. Additional studies are needed to elucidate the mechanisms by which females are protected from arterial stiffness to provide insight into its mechanisms and, ultimately, therapeutic targets for treating this pathology.

Do lactate levels in the emergency department predict outcome in adult trauma patients? A systematic review.

BACKGROUND: Serum lactate may be associated with clinical outcomes in trauma, even in the absence of physiological abnormality. Sensitive markers of injury and outcomes are needed to guide triage and management of trauma patients within the Emergency Department. We completed a systematic review to determine if lactate levels in adult trauma patients presenting to the Emergency Department were associated with clinical outcomes including mortality. METHODS: A systematic literature search was conducted in August 2014, updated in March 2016, using MEDLINE, Embase, and CINAHL. Abstracts and full texts were screened for inclusion by two independent reviewers using predetermined inclusion and exclusion criteria. Data extraction and quality assessment was performed by each reviewer using a standardized form. A total of 998 studies were screened; 28 studies were included and reviewed. RESULTS: The 28 studies recruited 44,154 adults in eight countries between 1997 and 2016. Twenty-one studies found a significant association between elevated Emergency Department lactate and risk of mortality. Three studies looked at lactate clearance; two showed poor clearance was an additional determinant of mortality, but the other found no association. Ten studies also found an association between elevated lactate and other clinical outcomes. These included injury severity, Intensive Care Unit admission, length of hospital stay, organ failure, respiratory complications, blood loss, blood product requirement, catecholamine support, or emergency operation. Two studies concluded that lactate levels do not affect management. CONCLUSIONS: This review shows that elevated Emergency Department lactate levels are associated with mortality and may be associated with other clinical outcomes in adult trauma patients. We conclude that lactate is a useful marker of outcome in trauma, in addition to current markers of severity. The potential roles of serial lactate measurement and lactate clearance require further research. LEVEL OF EVIDENCE: Systematic review, level III.

Trajectories of alcohol use and consequences in college women with and without depressed mood.

College students with depressed mood face heightened risk for experiencing drinking-related negative consequences. However, few studies have examined prospective patterns of alcohol consequences among depressed students. In the present investigation, we assessed how first-year college women's trajectories of heavy episodic drinking (HED) and alcohol consequences differed as a function of depressed mood at college entry. Participants were 233 heavy drinking incoming first-year college females (61% White) at a mid-sized West Coast University. Participants completed an online baseline survey, attended a single brief group intervention session, and completed 1- and 6-month post-intervention follow-up surveys. Depressed mood, alcohol consumption, and alcohol consequences were assessed at each time point. We employed latent growth curve analyses. Females with depressed mood, versus without depressed mood, experienced greater levels of alcohol consequences overall, particularly during transitions to college. However, contrary to hypotheses, participants with depressed mood (vs. without) exhibited significantly steeper declining trends in consequences, controlling for treatment condition, age, race, and ethnicity, and despite stable drinking levels, depressed mood, and use of protective behaviors over time. Potential explanations and suggestions for future research are discussed.