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Halder S.K.,Center for Womens Health Research | Goodwin J.S.,Meharry Medical College | Al-Hendy A.,Center for Womens Health Research
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: Uterine leiomyomas (fibroids) are the most common benign estrogen-dependent tumors of premenopausal women. TGF-β3 up-regulates the synthesis of many of extracellular matrix proteins that are associated with tissue fibrosis. Objective: To examine the effect of 1,25-dihydroxyvitamin D3 (vitamin D3) on TGF-β3-induced fibrosis-related protein expression in immortalized human uterine leiomyoma (HuLM) cells. Methods: HuLM cells were treated with TGF-β3 with or without vitamin D 3. Western blot analyses were employed to test the effect of vitamin D3 on TGF-β3-induced protein expression of collagen type 1, fibronectin, and plasminogen activator inhibitor-1 proteins. Western blots as well as immunofluorescence analyses were used to verify the effect of vitamin D3 on TGF-β3-induced Smad activation involved in extracellular matrix protein synthesis and deposition, which ultimately lead to tissue fibrosis. Results: We observed that TGF-β3 induced fibronectin and collagen type 1 protein expression in HuLM cells, and that effect was suppressed by vitamin D3. TGF-β3 also induced protein expression of plasminogen activator inhibitor-1, an important TGF-β target, in HuLM cells, which was also inhibited by vitaminD3. Additionally, TGF-β3 induced phosphorylation of Smad2 as well as nuclear translocation of Smad2 and Smad3 in HuLM cells, whereas vitamin D significantly reduced all these TGF-β3-mediated effects. Therefore, our results suggest that vitamin D3 has consistently reduced TGF-β3 effects that are involved in the process of fibrosis in human leiomyoma cells. Conclusion: Vitamin D 3 is an antifibrotic factor that might be potentially useful as a novel therapeutic for nonsurgical treatment of benign uterine fibroids. Copyright © 2011 by The Endocrine Society.


Huebschmann A.G.,Aurora University | Huebschmann A.G.,Center for Womens Health Research | Crane L.A.,Rocky Research | Belansky E.S.,Rocky Research | And 4 more authors.
Diabetes Care | Year: 2011

OBJECTIVE - Physical activity is a cornerstone of treatment for diabetes, yet people with diabetes perform less moderate and vigorous physical activity (MVPA) than people without diabetes. In contrast, whether differences in walking activity exist has been understudied. Diabetes-specific barriers to physical activity are one possible explanation for lower MVPA in diabetes.We hypothesized that people with diabetes would perform less walking and combined MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent, compared with people without diabetes. RESEARCH DESIGN AND METHODS - We surveyed 1,848 randomly selected rural Colorado adult residents by telephone from 2002 to 2004. Respondents reported weekly walking and MVPA duration and their likelihood of increasing physical activity if each of seven barriers was theoretically absent. RESULTS - People with diabetes (n = 129) had lower odds of walking and MVPA than people without diabetes (walking: adjusted odds ratio 0.62 [95% CI 0.40-0.95]; MVPA: adjusted odds ratio 0.60 [0.36-0.99]; ≥10 vs. <10 min/week, adjusted for age, sex, BMI, and ethnicity). Respondents with diabetes reported fear of injury as a barrier to physical activity more often than respondents without diabetes (56 vs. 39%; P = 0.0002), although this relationship was attenuated after adjusting for age and BMI (adjusted odds ratio 1.36 [0.93-1.99]). CONCLUSIONS - Although walking is a preferred form of activity in diabetes, people with diabetes walk less than people without diabetes. Reducing fear of injury may potentially increase physical activity for people with diabetes, particularly in older and more overweight individuals. © 2011 by the American Diabetes Association.


Bergman B.C.,Anschutz Medical Campus | Nadeau K.J.,Center For Womens Health Research | Cree-Green M.,Center For Womens Health Research
American Journal of Physiology - Endocrinology and Metabolism | Year: 2016

Advancing diabetes care requires accurate physiological assessments. Hyperinsulinemic clamps with stable isotope tracers can simultaneously measure insulin’s ability to suppress lipolysis and hepatic glucose release. Traditionally, these methods require an assessment of basal glucose and glycerol rate of appearance (Ra). Basal Ra is challenging to measure in insulin-dependent diabetes, where exogenous insulin required to maintain normoglycemia can raise peripheral insulin concentrations sufficiently to suppress basal Ra. Thus we identified two alternative statistical approaches to describe changes in glucose and glycerol Ra that are less reliant on basal assessments. Sixteen youths (4 type 1 diabetic, 4 type 2 diabetic, 4 lean controls, and 4 obese nondiabetic) underwent a four-phase (“basal” and 10, 16, and 80 mU·m2·min‑1) hyperinsulinemic euglycemic clamp with glucose and glycerol tracers. Glucose and glycerol Ra were calculated per phase. A statistical method, the standard two-stage (STS) algorithm, was applied to the individual log insulin vs. Ra curves to calculate a single predicted Ra value. A population-based mixed-effects model (MEM) compared the group average Ra with log insulin curves and described individual deviations from group means and was used to calculate individual predicted Ra. Both models were applied to the participant data, and predicted Ras at the mean insulin concentration per phase (10 for glycerol, 16 for glucose) were calculated, with good agreement between observed and predicted values. In our data set, the MEM was better able to detect group differences. Both STS and MEM can model lipolysis and endogenous glucose release in insulin-dependent states when basal Ra cannot be accurately measured. © 2016 the American Physiological Society.


Huebschmann A.G.,University of Colorado at Denver | Huebschmann A.G.,Center for Womens Health Research | Regensteiner J.G.,University of Colorado at Denver | Regensteiner J.G.,Center for Womens Health Research
Vascular Medicine | Year: 2011

Type 2 diabetes mellitus (T2D) is an example of a disease process that results in decrements in function additional to those imposed by the inexorable 'primary aging' process. These decrements due to disease, rather than primary aging, can be termed 'secondary aging', and include the premature development (as early as adolescence) of asymptomatic preclinical cardiovascular abnormalities (e.g. endothelial dysfunction, arterial stiffness, diastolic dysfunction), as well as impaired exercise performance. These abnormalities are important, as they are associated with greater cardiovascular morbidity and mortality in people with and without T2D. A better understanding of the pathophysiology of secondary cardiovascular aging in people with T2D is warranted, and an evaluation of the benefits of existing treatments for these abnormalities is useful (e.g. exercise training). The focus of this review is to discuss the data relevant to the following key postulates: (a) T2D causes premature cardiovascular aging; (b) in contrast to primary cardiovascular aging, the premature cardiovascular aging of T2D may be modifiable with exercise. The exercise-focused perspective for this review is appropriate because impairments in exercise performance are markers of premature cardiovascular aging in T2D, and also because exercise training shows promise to attenuate some aspects of cardiovascular aging during the preclinical stage. © SAGE Publications 2011.


PubMed | Center for Womens Health Research and Aurora University
Type: Journal Article | Journal: BMJ open diabetes research & care | Year: 2015

Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM.We enrolled overweight, sedentary women aged 50-75years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration.VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30W: Control, 10.43.2, T2DM, 11.72.3, p=0.08; 35% VO2peak: Control, 11.10.5, T2DM, 12.10.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30W and 35% VO2peak).Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought.NCT00785005.


PubMed | Meharry Medical College and Center for Womens Health Research
Type: | Journal: Clinical, cosmetic and investigational dentistry | Year: 2016

Hypertension is a chronic illness affecting more than a billion people worldwide. The high prevalence of the disease among the American population is concerning and must be considered when treating dental patients. Its lack of symptoms until more serious problems occur makes the disease deadly. Dental practitioners can often be on the frontlines of prevention of hypertension by evaluating preoperative blood pressure readings, performing risk assessments, and knowing when to consider medical consultation of a hypertensive patient in a dental setting. In addition, routine follow-up appointments and patients seen on an emergent basis, who may otherwise not be seen routinely, allow the oral health provider an opportunity to diagnose and refer for any unknown disease. It is imperative to understand the risk factors that may predispose patients to hypertension and to be able to educate them about their condition. Most importantly, the oral health care provider is in a pivotal position to play an active role in the management of patients presenting with a history of hypertension because many antihypertensive agents interact with pharmacologic agents used in the dental practice. The purpose of this review is to provide strategies for managing and preventing complications when treating the patient with hypertension who presents to the dental office.


PubMed | Center for Womens Health Research and Anschutz Medical Campus
Type: Journal Article | Journal: American journal of physiology. Endocrinology and metabolism | Year: 2016

Advancing diabetes care requires accurate physiological assessments. Hyperinsulinemic clamps with stable isotope tracers can simultaneously measure insulins ability to suppress lipolysis and hepatic glucose release. Traditionally, these methods require an assessment of basal glucose and glycerol rate of appearance (Ra). Basal Ra is challenging to measure in insulin-dependent diabetes, where exogenous insulin required to maintain normoglycemia can raise peripheral insulin concentrations sufficiently to suppress basal Ra. Thus we identified two alternative statistical approaches to describe changes in glucose and glycerol Ra that are less reliant on basal assessments. Sixteen youths (4 type 1 diabetic, 4 type 2 diabetic, 4 lean controls, and 4 obese nondiabetic) underwent a four-phase (basal and 10, 16, and 80 mUm(2)min(-1)) hyperinsulinemic euglycemic clamp with glucose and glycerol tracers. Glucose and glycerol Ra were calculated per phase. A statistical method, the standard two-stage (STS) algorithm, was applied to the individual log insulin vs. Ra curves to calculate a single predicted Ra value. A population-based mixed-effects model (MEM) compared the group average Ra with log insulin curves and described individual deviations from group means and was used to calculate individual predicted Ra. Both models were applied to the participant data, and predicted Ras at the mean insulin concentration per phase (10 for glycerol, 16 for glucose) were calculated, with good agreement between observed and predicted values. In our data set, the MEM was better able to detect group differences. Both STS and MEM can model lipolysis and endogenous glucose release in insulin-dependent states when basal Ra cannot be accurately measured.


Cree-Green M.,Aurora University | Cree-Green M.,Center For Womens Health Research | Newcomer B.R.,University of Alabama at Birmingham | Coe G.,Aurora University | And 7 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2015

Hyperandrogenic syndrome (HAS) is associated with insulin resistance (IR) and type 2 diabetes. Muscle IR in type 2 diabetes is linked with defects in mitochondrial oxidative capacity. In vivo muscle mitochondrial function has not been studied in HAS, especially in youth, who are early in the disease process. Our goal was to measure muscle mitochondrial oxidative function and peripheral IR in obese youth with HAS. Obese girls without HAS [n 22, age 15(13,17) yr, BMI Z-score 2.05 ±0.37] and with HAS [n 35, age 15(14,16) yr, BMI Z-score 2.18±0.30] were enrolled. Mitochondrial function was assessed with 31phosphorus MR spectroscopy before, during, and after near-maximal isometric calf exercise, and peripheral IR was assessed with an 80 mU·m-2·min-1 hyperinsulinemic euglycemic clamp. Girls with HAS had higher androgens [free androgen index 7.9(6.6,15.5) vs. 3.5(3.0,4.0), P < 0.01] and more IR [glucose infusion rate 9.4(7.0, 12,2) vs. 14.5(13.2,15.8) mg·kg lean-1·min-1, P < 0.01]. HAS girls also had increased markers of inflammation including CRP, platelets, and white blood cell count and higher serum free fatty acids during hyperinsulinemia. Mitochondrial oxidative phosphorylation was lower in HAS [0.11(0.06,0.19) vs. 0.18(0.12,0.23) mmol/s, P < 0.05], although other spectroscopy markers of mitochondrial function were similar between groups. In multivariate analysis of the entire cohort, IR related to androgens, oxidative phosphorylation, and free fatty acid concentrations during hyperinsulinemia. These relationships were present in just the HAS cohort as well. Obese girls with HAS have significant peripheral IR, which is related to elevated androgens and free fatty acids and decreased mitochondrial oxidative phosphorylation. These may provide future options as targets for therapeutic intervention. © 2015 the American Physiological Society.


Kolehmainen C.,University of Wisconsin - Madison | Brennan M.,University of Wisconsin - Madison | Filut A.,University of Wisconsin - Madison | Isaac C.,Mercer University | And 2 more authors.
Academic Medicine | Year: 2014

PURPOSE: Ineffective leadership during cardiopulmonary resuscitation ("code") can negatively affect a patient's likelihood of survival. In most teaching hospitals, internal medicine residents lead codes. In this study, the authors explored internal medicine residents' experiences leading codes, with a particular focus on how gender influences the code leadership experience. METHOD: The authors conducted individual, semistructured telephone or in-person interviews with 25 residents (May 2012 to February 2013) from 9 U.S. internal medicine residency programs. They audio recorded and transcribed the interviews and then thematically analyzed the transcribed text. RESULTS: Participants viewed a successful code as one with effective leadership. They agreed that the ideal code leader was an authoritative presence; spoke with a deep, loud voice; used clear, direct communication; and appeared calm. Although equally able to lead codes as their male colleagues, female participants described feeling stress from having to violate gender behavioral norms in the role of code leader. In response, some female participants adopted rituals to signal the suspension of gender norms while leading a code. Others apologized afterwards for their counternormative behavior. CONCLUSIONS: Ideal code leadership embodies highly agentic, stereotypical male behaviors. Female residents employed strategies to better integrate the competing identities of code leader and female gender. In the future, residency training should acknowledge how female gender stereotypes may conflict with the behaviors required to enact code leadership and offer some strategies, such as those used by the female residents in this study, to help women integrate these dual identities.


Price E.,Center for Womens Health Research | Follen M.,Institute for Womens Health and Leadership
Gender Medicine | Year: 2012

The Woman's Medical College of Pennsylvania was a groundbreaking institution and an ancestor to the Drexel University College of Medicine. The tradition of the Woman's Medical College lives on in the form of education and leadership programs dedicated to medical training for women. © 2012 Elsevier HS Journals, Inc. All rights reserved.

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