Aims: To determine whether low-dose calcitriol attenuates atherosclerosis in apoE-null mice and, if so, through which predominant mechanism. Methods: Starting at the age of 6 weeks, mice received ...intraperitoneal injections of either 0.25 ng/g body weight of calcitriol or the vehicle, every other day for 8 weeks. Results: Calcitriol treatment resulted in 35% reduction of atherosclerosis at the aortic sinus, and in a significant decrease in blood pressure. These effects were possibly mediated by downregulation of the renin-angiotensin system (RAS), as there was a 64% decrease in the aortic level of renin mRNA. None of the other components of the RAS or the prorenin receptor were affected by treatment. Low-dose calcitriol treatment did not modify the plasma level of monocyte chemoattractant protein-1, interferon γ, interleukin-4 and interleukin-10, which were similar in control and treated mice. Likewise, there was no difference in the percentage of splenic Foxp3+ regulatory T cells. Calcitriol treatment resulted in an unfavorable metabolic profile (glucose and lipids), as determined after a limited fast, a difference that disappeared after food was withheld for a longer time. Conclusions: At a relatively low dosage, calcitriol attenuates the development of atherosclerosis in apoE-null mice, most probably by down regulation of RAS, and not through immunomodulation; however, even at this low dose, calcitriol appears to elevate calcium and to have potentially adverse metabolic effects. Exploring the potential antiatherogenic effects of non-calcemic and safer analogues is therefore warranted.
What happens when a teaching method designed around learning new technologies is applied to artmaking for teens in an art museum? How do technology and traditional artmaking techniques connect in the ...studio? What role does mentorship play? What happens to participants after they leave the program? These questions are central to this case study, which looks at the Teen Program at the Yale University Art Gallery in New Haven, Connecticut. The Gallery adopted Hanging Out, Messing Around, Geeking Out (HOMAGO) as the primary educational method for the program. HOMAGO is a free-choice method that allows teens to learn skills at their own pace through interactions with peers and mentors, rather than formal instruction. By creating spaces for groups to spend time together and experiment at their own pace, teens learned new skills through deep involvement in projects connected to their specific interests.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Inhibition of endothelial nitric oxide synthase (eNOS) accelerates atherosclerosis in ApoE-null mice by impairing the balance between angiotensin II (AII) and NO. Our previous data suggested a role ...for PPARα in the deleterious effect of the renin-angiotensin system (RAS). We tested the hypothesis that ApoE-null mice lacking PPARα (DKO mice) would be resistant to the proatherogenic effect of NOS inhibition. DKO mice fed a Western diet were immune to the 23% worsening in aortic sinus plaque area seen in the ApoE-null animals under 12 weeks of NOS inhibition with a subpressor dose of L-NAME, P=0.002. This was accompanied by a doubling of reactive oxygen species (ROS-) generating aortic NADPH oxidase activity (a target of AII, which paralleled Nox1 expression) and by a 10-fold excess of the proatherogenic iNOS, P<0.01. L-NAME also caused a doubling of aortic renin and angiotensinogen mRNA level in the ApoE-null mice but not in the DKO, and it upregulated eNOS in the DKO mice only. These data suggest that, in the ApoE-null mouse, PPARα contributes to the proatherogenic effect of unopposed RAS/AII action induced by L-NAME, an effect which is associated with Nox1 and iNOS induction, and is independent of blood pressure and serum lipids.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: Arterial wall stiffening is linked to a heightened risk of cardiovascular morbidity and mortality. To date, the influence of changes in nutritional components on arterial flexibility, ...during intentional weight loss program in patients with metabolic syndrome (MS), remains unexplored Methods: 69 MS (38/31m/f) participants were enrolled into a 1-year weight loos program. Nutritional recommendation consisted of moderate low calorie/high protein Mediterranean diet. Baseline characteristics: age 53.0±12.2 years; (BMI) 34.3±4.0 kg/m2; Flow Mediated Dilation % (FMD) 7.62±4.65; Pulse Wave Velocity (PWV; m/sec) 9.2±2.5; common carotid artery (CCA pmeters) 778±139; Insulin 28±19.5 (mU/mL); HbA1C 5.8±0.5%. Asymmetric Dimethylarginine (ADMA) 0.535±0.16 (pmol/L); L Arginine 44.9±16.15 (pmol/L); Nutritional components were registered over 7 days before and by 1year of treatment, with detailed questionnaires analyzed by software Results: Within the 1 year, BMI declined by 9.1±6.4% (p= 0.000). Correlations existed between the decrease in PWV and decrease in dietary energy (r=-0.304 p=0.034) and increase in dietary Zinc (r=0.350 p=0.014) and decrease in blood creatinine (r=0.383 p=0.009). Further correlations were found between the decrease in CCA and an increase in L Arginine (r=0.296 p=0.025), increase in protein intake (r=- 0.265 p=0.032), decreases in blood glucose (r=-0.278 p=0.024) and cholesterol (r=-0.257 p=0.045). FMD increase correlated with the decrease in carbohydrate intake (r= 0.255 p= 0.040), increase in potassium intake (r= -0.325 p= 0.008), and decrease in blood insulin (r= 0.333 p= 0.026). There was a correlation between Insulin reduction and ADMA reduction (r= 0.364 p= 0.021) Conclusions: Changes in food components, including overall macro-and micronutrients, are associated with improved vascular flexibility
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
"Communities of practice" is a concept employed by Etienne and Beverly Wenger-Trayner (2015) to refer to "groups of people who share a… passion for something they do and learn how to do it better as ...they interact regularly" (p. 1). In the museum context, a community-of-practice model provides educators the opportunity to improve their teaching practice through collaboration--namely, the sharing of ideas, reflections, and strategies among colleagues. However, because art museums are typically not designed or built with children younger than 5 in mind and have been "the most reluctant type of museum to embrace childhood visitors" (Andre et al., 2017, p. 62), art-viewing and art-appreciation experiences in museums have traditionally been "an overlooked component" of early childhood education (Eckhoff, 2008, p. 471). This article examines e how museums and early childhood educators are distinct communities of practice that can converge around the shared interest of early childhood art education to deepen their expertise. It also examines how young children's experiences inform the work of communities of practice. Finally, the article examines how symbiotic communities of practice inform art museums' offerings for and interactions with children younger than 5 by complementing artmaking experiences in the home or childcare setting with art-viewing and art-appreciation experiences in the museum.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
6.
Weigh More, Lose Less Bone Tai, Brurya; Shefer, Gabi; Sack, Jessica ...
Obesity (Silver Spring, Md.),
11/2023, Volume:
31
Journal Article
Peer reviewed
Background: Several reports indicated that intentional weight loss can result in reduction in bone mineral density (BMD), particularly in postmenopausal women, and older individuals. This is a ...post-hoc analysis of a prospective multidisciplinary weight loss trial, in search of predictors of bone loss in the Metabolic Syndrome (MS). Methods: 73 MS subjects (ATPIII criteria; F/M = 34/39) participated in a 1-year intensive multidisciplinary treatment, based on personalized physical training and a low calorie/high protein Mediterranean diet. Baseline (±SD): age 53.3 ± 11.2 years; weight 98.6 kg ± 16.8; BMI 34.4 ± 3.8 kg/m2; lean body mass (LBM) 55.48 kg ± 11.66 kg; Spine BMD 1.21 ± 016 g/cm2, femur neck BMD 0.99 ± 0.13 g/cm2. Results: By the end of 1-year BMI declined by 9.1% (p < 0.001); LBM declined by 2.68% (p < 0.001). There were no significant overall changes in spine or femur BMD; no difference in the change in BMD between participants under the age of 50 years or above 51 years, and between male and female subjects. Despite the lack of overall change in BMD during weight loss, when individual changes in spinal BMD were analyzed, participants who clustered above the median post-treatment versus pre-treatment BMD level, showed a higher initial BMI compared to participants whose change in spinal BMD was below the median level (BMI 35.6 ± 3.6 vs. 32.5 ± 3.52 kg/m2, respectively (p < 0.0001). Conclusions: In subjects with MS undergoing intensive and closely supervised multidisciplinary intentional 1 year weight loss program, higher initial weight is associated with lesser spine bone loss.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the ...cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function.
Methods
Twenty-nine subjects with acromegaly (11 males, 52 ± 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD).
Results
IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 ± 1.1 in patients with active disease versus 0.7 ± 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 ± 2.7 % in active acromegaly, 4.4 ± 3.3 % in controlled acromegaly and 7.5 ± 3.8 % in controls;
p
= 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r = 0.4;
P
= 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46;
p
= 0.017) and negatively with small vessel compliance (r = −0.44,
p
= 0.02).
Conclusions
Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction: Mitochondrial DNA mutation is a rare cause for diabetes mellitus (DM) and deafness that is often misdiagnosed as type 1 or type 2 DM. Unique management issues, associated comorbidities ...and fertility plans require proper diagnosis. Proband: a 25 year-old female presented with a fasting glucose 205 mg/dl, Hb A1c 8.5% with intolerance to metformin. She has been previously diagnosed with sensorineural hearing loss. Her physical examination was unremarkable, except for a BMI of 20kg/m
2
and a short stature. Her parents were not blood-related. The family history was notable for several relatives with either diabetes or deafness. Her twin sister had prediabetes, her older sister had deafness, her brother had muscle cramps and her mother had both DM and hearing loss, and was also diagnosed with "fibromyalgia". From the mother side; her grandmother had DM, her aunt had deafness and her daughter had DM, 2 uncles had DM. GAD antibodies, Islet cell antibodies and Zinc transporter 8 antibodies were negative. Renal function was normal. She responded well to basal insulin treatment, with an achieved Hb A1c of 7%. Her genetic workup identified a mutation in the mitochondrial DNA m.3243A>G which is associated with MIDD (maternally inherited diabetes and deafness) and MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes). The following specific recommendations were made, which differ from the standard practice and guidelines in the care of classical type 1 or type 2 diabetes: 1) avoid metformin; 2) rigidly maintain adequate carbohydrate consumption when ill, as stroke- like episodes have been described in this condition during acute illness when carbohydrate supply was inadequate; 3) use Coenzyme Q10 which might enhance insulin secretion and potentially improve symptoms of myopathy. 4) attempt not to postpone fertility due to the risk of premature ovarian failure; 5) for pregnancy planning, consider "three parent IVF" with mitochondria and cytoplasm from a donated ovum, thus potentially avoiding transmitting the defect. Conclusion: Diagnosis of MIDD should be considered in subjects with family history of premature deafness and diabetes, not necessarily in the same subjects. The correct diagnosis may offer multiple therapeutic advantages. With accurate genetic diagnose, appropriate therapy, family screening, genetic counseling and surveillance for existing and future complications can be applied.
Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1‐year multidisciplinary intervention on BPV in patients with the ...metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty‐four nondiabetic patients underwent clinical and biochemical profiling, 24‐hour ambulatory BP monitoring (ABPM), body composition, carotid intima‐media thickness, and carotid‐femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high‐variability group had higher values of low‐density lipoprotein and leg fat. The 1‐year intervention resulted in weight reduction but not BP‐lowering. BPV declined in the high‐variability group in association with lowering of PWV, C‐reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high‐density lipoprotein cholesterol. A multidisciplinary intervention independent of BP‐lowering normalized BPV, lowered PWV, and enhanced metabolic control.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background:
Diabetic subjects with life-long massive obesity that have reached old age, often develop heart failure, severe hypertension and renal failure. Fluid retention necessitates increasing ...doses of diuretics, with further decline in renal function.
Rationale:
In older obese subjects who failed numerous standard dietary attempts and have developed complications which preclude bariatric surgery, prolonged periods of long and repetitive intermittent fasting may lead to a) regular fasting diuresis, such that will lessen the need for diuretics; b) fat loss. Both may ameliorate intractable comorbidities.
Goal:
To examine whether or not complete intermittent fasting can positively impact fluid overload, functional status and life quality in old obese diabetic subjects with heart and renal failure.
Methods:
Two 77y/o outpatient men were instructed to avoid any caloric intake, but consume calorie-free fluids ad libitum for 36 hours (last evening meal on the pre-fasting day; first next meal◊ breakfast on the post- fasting day), twice a week (total fasting hours 72/168 weekly hours) over 17 patient A; A and 13 months patient B; B. Insulin, GLP-1 analogs and oral drugs were individually adjusted for each fasting interval.
Results: Extent of Experience
: We accrued experience of 30 patient months.
Effects:
within this time frame, the following effects were observed: 1) Weight (and BMI) declined from 92 to 77kg (37.8->31.6kg/m2) and 108 to 84.6kg (40◊31kg/m2) in A, and B, respectively. 2) Heart failure (diastolic dysfunction with preserved systolic function) and functional capacity: we recorded: I. Improvement from NYHA class IV and III to II in B, A); II. Cessation of pulmonary edema events ( vs. 2 events/ patient in the preceding year); III: decrease >50% in the doses of furosemide; d/c of IV furosemide; IV: disappearance of peripheral edema; 3) Improvement in renal function in B (eGFR 15.7-->36.7cc/min) and stabilization in A (35cc/ml); 4) Improvement in anemia: hemoglobin rose by 2Gr% in B and 0.8gr% in A; 5) HgA1C was unchanged in A (7.8, 7.7%) in A and declined in B (6.7% ->5% in B). 5) Hypertension was not affected.
Safety:
hypoglycemia was not detected with regular, multiple point home glucose monitoring on the fasting days. Hyperkalemia was present
a priori
in both patients, required continuous f/u and treatment, but no other electrolyte and mineral abnormalities were seen.
Compliance:
Several events of partial/complete skipping of fasting resulted in fluid accumulation and leg edema, following which self-reported compliance has been nearly complete. At the present time, these subjects refuse to get off the protocol. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.
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