SEM Age Research Articles

Precise health perspectives: Unraveling the interplay of reproductive factors in hormone receptor–positive and triple-negative breast cancer among Bangladeshi women.

e22503 Background: Breast cancer is a major cause of cancer-related deaths in Bangladesh, with an incidence rate of 22.5 per 100,000 females per year. Urbanization is linked to the increasing incidence of breast cancer, altering lifestyles and reproductive behaviors. Reproductive factors play a key role in breast cancer risk, with variations between TNBC and Hr+BC. This study aims to investigate the relationship between TNBC and Hr+BC and reproductive factors among Bangladeshi women to provide valuable insights for breast cancer prevention and management in the region. Methods: Conducted in a tertiary hospital-based setting, our survey included 1000 adult Bangladeshi females aged 18 or older. Among them, 250 had TNBC, 250 had Hr+BC, and the remaining 500 were non-cancer individuals. Propensity score matching (PSM) was utilized to match the age and age of menarche of 500 healthy individuals with 250 TNBC and 250 Hr+BC individuals separately. The presence of TNBC or Hr+BC was confirmed through participants' previous histopathology reports. Detailed reproductive characteristics and demographics were collected using a structured questionnaire. Significant variables identified in the bivariate model were included in the adjusted multivariable multinomial logistic regression. Results: Demographic and reproductive characteristics in the Hr+BC, TNBC, and healthy groups were analyzed. The mean ±SEM age was Hr+BC (44.96±0.65), TNBC (42.74±0.65), and healthy (39.31±0.55) years. Patients with Hr+BC and TNBC, compared to healthy individuals, were older, with delayed first marriage and first birth, and more abortions. Both demographic and reproductive factors correlated with Hr+BC and TNBC, with higher likelihood in postmenopausal, irregular menstruation, vaginal delivery, breastfeeding > 6 months, and hormonal contraceptive use. Reproductive factors associated with Hr+BC and TNBC risk were outlined. The adjusted model revealed delayed menarche increased Hr+BC risk by 1.71 times (OR 1.71, 95% CI 1.19-2.44) but decreased TNBC risk by 30% (OR 0.70, 95% CI 0.52-0.95). Longer time between first marriage and first birth (OR 1.40, CI 95% 1.10-1.78), irregular menstruation (OR 2.83, 95% CI 1.31-6.10), and hormonal contraceptive use (OR 5.68, 95%1.52-21.25) increased Hr+BC risk; pre-obesity decreased risk (OR 0.36 95% CI 0.18-0.72). Irregular menstruation (OR 4.30, 95% CI1.87-9.42) and hormonal contraceptive use (OR 8.54, 95% CI 1.81-40.14) increased TNBC risk. Higher abortions raised TNBC risk (OR 2.27, 95% CI 01.30-3.98) but not Hr+BC. Living in rural Bangladesh increased risk for both Hr+BC (4.81 times) and TNBC (16.77 times). Conclusions: Our findings highlight the significant impact of reproductive factors on Hr+BC and TNBC development in Bangladeshi women, emphasizing variations in risk profiles among different breast cancer types.

Neural responses to oral administration of erythritol vs. sucrose and sucralose explain differences in subjective liking ratings

IntroductionHigh sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs). MethodsWe performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking. ResultsLiking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability. ConclusionWe found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns.

THU074 Plasma Spexin In Metabolic Syndrome Related To Adult Growth Hormone Deficiency: A Cross-sectional Study

Abstract Disclosure: E. Vergani: None. A. Oliva: None. C. Bruno: None. D. Currò: None. A. Mancini: None. Adult growth hormone deficiency (aGHD) shares with metabolic syndrome some clinical features such as higher fat mass percentage, increased total cholesterol, LDL, triglycerides, reduced HDL, and higher risk of developing type 2 diabetes mellitus and cardiovascular complications. Spexin, also known as neuropeptide Q, is a 14-aminoacid polypeptide, related to the galanin-kisspeptin family, produced in several human tissues. It is also secreted along with insulin by pancreatic beta cells; via paracrine effects they blunted reciprocal secretion. In type 2 diabetes mellitus spexin is closely correlated to fasting and post prandial glucose, glycosylated hemoglobin and HOMA index. Moreover, spexin infusion seems to ameliorate ALT and AST levels in non-alcoholic fatty liver disease. Given its controversial role in condition of metabolic impairment, we aimed to evaluate spexin plasmatic levels in aGHD. Thirty-eight subjects were included in the study, 18 aGHD patients (7 females and 11 males) and 20 healthy controls (12 females and 8 males). aGHD was diagnosed by a GHRH plus arginine test. Etiologies of GHD were as follows: 7 empty sellas, 5 post-surgical hypopituitarism, and 6 idiopathic with negative MRI scans. GHRH plus arginine stimulation tests were repeated twice in idiopathic aGHD to confirm the diagnosis. They were evaluated for glucose and insulin, HOMA and QUICKI index, total/LDL/HDL cholesterol, triglycerides, uric acid and IGF-1. Spexin was measured by ELISA, according to manufacturers’ protocols. Fat mass percentage was evaluated by DXA. Mean±SEM age of aGHD group was 59.7±2.7 years, while BMI was 30.2±2.2 kg/m2; control group aged 47.1±2.5 years, while BMI was 24.5±0.9 kg/m2. As expected, aGHD patients showed higher HOMA index, triglycerides and lower HDL than controls. Furthermore mean±SEM fat mass percentage was significantly higher in aGHD than controls (44.41±3.15 vs 32.2±3.64). Spexin levels were similar in the two groups (aGHD 1.17±0.21 vs controls 1.25±0.10 ng/ml). significant correlations were found in both populations. These results, although preliminary, seem to exclude a possible role of spexin in aGHD; however, spexin could represent another possible element of differentiation between aGHD and metabolic syndrome. Such controversial topic requires further evaluations. Presentation: Thursday, June 15, 2023

OR17-5 Kisspeptin Increases Penile Tumescence and Sexual Brain Processing in Men with Hypoactive Sexual Desire Disorder

Abstract Background Hypoactive Sexual Desire Disorder (HSDD) is associated with dysfunctional brain activation in regions governing sexual responses, resulting in a deficiency or absence of sexual desire with marked distress. It is of major clinical importance given it affects 8% of men with detrimental effects on quality of life, interpersonal relationships and fertility, but so far has no licensed treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target owing to its emerging role in modulating reproductive behaviour in animal models and healthy men. However, there are no studies examining its effects in HSDD. To address this, we performed the first clinical study of kisspeptin in men with HSDD. Methods We examined the effects of kisspeptin administration (vs placebo) on brain activity during short and long erotic video tasks using functional MRI in 32 men with HSDD (mean ±SEM age 37.9 ±1.5 y, BMI 24.9 ±1.0 kg/m2). The short video task used 20-second segments of erotic video with non-erotic video as control. During the long video task, participants viewed a continuous eight-minute erotic video. To provide functional and behavioural relevance for the associated fMRI brain responses during the long erotic video, simultaneous penile tumescence and subjective level of arousal were recorded. Participants also completed psychometric and behavioural questionnaires. Standard analysis methods were used for fMRI data from the short videos task, and the long videos task used regressors derived from the subjective arousal and penile tumescence data. The statistical threshold used for both was Z=2.3, p &amp;lt; 0.05 (cluster-corrected). Results In response to visual erotic stimuli, kisspeptin administration significantly increased penile tumescence during the long video task compared to placebo, with kisspeptin increasing penile tumescence by 56% at six-minutes (p=0.002). In addition, kisspeptin increased participant-reported happiness about sex (p=0.02). During both video tasks, kisspeptin significantly modulated brain activity compared to placebo in key structures of the sexual-processing network, providing a mechanistic pathway for the increases in physiological and behavioural measures. In response to short erotic videos, kisspeptin enhanced left middle frontal gyrus and left anterior cingulate activity, and decreased activity in bilateral parahippocampus (all p&amp;lt;0.05). During the long video task, kisspeptin enhanced right fusiform gyrus and bilateral visual cortex activity, and decreased left frontal pole, right posterior cingulate and bilateral precuneus activity (all &amp;lt;0.05). Additionally, we observed positive correlations between the effects of kisspeptin on aforementioned brain activity and psychometric parameters of sexual desire and arousal (all p&amp;lt;0.01). Conclusion Collectively, we demonstrate for the first time that kisspeptin administration in men with HSDD increases penile tumescence and psychometric measures of sexual desire and arousal by modulating sexual brain processing. Taken together, our data suggest that kisspeptin-based therapeutics may offer a novel, effective and much-needed clinical strategy for men with HSDD. Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.

RF34 | PMON222 Reproductive Hormone Secretion is Increased by Intranasal Kisspeptin in Humans

Abstract Background Kisspeptin is a critical activator of hypothalamic gonadotrophin releasing hormone (GnRH) neurons and has significant potential to treat common reproductive disorders. To date, kisspeptin has solely been administered to humans via the intravenous or subcutaneous routes, however intranasal administration could offer a novel non-invasive delivery route, which is preferred by patients. We therefore sought to determine the effects of intranasal kisspeptin on reproductive hormone release in humans for the first time. Methods Randomised, double-blinded, placebo-controlled, cross-over study in 12 healthy men (mean±SEM age 28.3±1.7 yrs; BMI 24.5±0.7 kg/m2). After monitored self-administration of intranasal kisspeptin-54 (3.2, 6.4, 12.8 and 25.6 nmol/kg) or 0.9% saline, serum reproductive hormone levels were measured every 15 minutes for four hours. Subsequently, four women (mean age 29.8±3.7 yrs; BMI 21.2±1.1 kg/m2) with hypothalamic amenorrhoea (HA) attended for the same protocol comparing intranasal kisspeptin-54 (12.8 nmol/kg) and 0.9% saline. Mean ±SEM was presented unless otherwise stated. Time profiles of hormone levels during the four-hour study were compared using two-way ANOVA with Bonferroni's multiple comparison test. Multiple means were compared using one-way ANOVA with Bonferroni's multiple comparison test. Results In healthy men, intranasal kisspeptin dose-dependently increased mean luteinising hormone (LH) levels at doses between 3.2-12.8 nmol/kg (p=0.008 and &amp;lt;0.0001 for 6.4 and 12.8 nmol/kg vs saline, respectively), with the maximal rises occurring at 30-45 minutes post-administration. Correspondingly, the area under the curve (AUC) for the LH change was significantly elevated following all doses of kisspeptin compared to saline (saline: -25.4±70.5 h.IU/L; 3.2 nmol/kg: 172.2±64.2 h.IU/L [p=0.03]; 6.4 nmol/kg: 300.2±79.2 h.IU/L [p=0.002]; 12.8 nmol/kg: 595.7±98.3 h.IU/L [p=0.001]; 25.6 nmol/kg: 549.0±108.6 h.IU/L [p&amp;lt;0.0001]). Follicle stimulating hormone (FSH) levels followed a similar trajectory to LH in response to intranasal kisspeptin. Moreover, kisspeptin at 12.8 nmol/kg increased serum testosterone from 120 minutes onwards (p=0.02), with a maximal change from baseline of 4.9±0.7 nmol/L (p=0.03). In women with HA, intranasal kisspeptin increased mean LH (p=0.002 vs saline), with the peak levels occurring at 30-45 minutes post-administration. The AUC for the LH change was 508.4±77.5 h.IU/L (p=0.02 vs saline AUC for LH). The maximal LH change from baseline was 4.1±0.9 IU/L compared to 0.2±0.4 IU/L for saline (p=0.03). Intranasal kisspeptin increased mean FSH (p=0.01 vs saline). No significant changes in downstream serum oestradiol or progesterone were observed during the acute four-hour study. Conclusion We report the first investigation of the effects of intranasal kisspeptin delivery on reproductive hormone release in humans. Our results demonstrate that intranasal kisspeptin robustly and dose-dependently stimulates reproductive hormone release in healthy men and crucially in a patient-group of women with hypogonadism. Given the ongoing development of kisspeptin therapeutics, intranasal kisspeptin therefore offers a novel, safe, effective and non-invasive route of administration for the management of reproductive disorders. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:36 p.m. - 12:41 p.m.

Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial

Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen+Cal, n=40, mean±SEM age: 21.3±0.5 y; weight: 55.0±1.0kg; BMI: 20.4±0.3kg/m2) who increased energy intake 20%-40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n=36; mean±SEM age: 20.7±0.5 y; weight: 59.1±1.3kg; BMI: 21.3±0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed. Oligo/Amen+Cal improved energy status [increased body mass (2.6±0.4kg), BMI (0.9±0.2 kg/m2), fat mass (2.0±0.3kg), body fat percentage (2.7%±0.4%), and insulin-like growth factor 1 (37.4±14.6ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P<0.05). Total body and spine aBMD remained unchanged (P>0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006g/cm2; 95% CI: -0.011, -0.0002g/cm2 ; time main effect P=0.043) and month 12 (-0.011g/cm2; 95% CI: -0.021, -0.001g/cm2; time main effect P=0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006g/cm2; 95% CI: -0.011, -0.002g/cm2; time main effect P=0.004). Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen.This trial was registered at clinicaltrials.gov as NCT00392873.

Red Raspberry and Fructo-Oligosaccharide Supplementation, Metabolic Biomarkers, and the Gut Microbiota in Adults with Prediabetes: A Randomized Crossover Clinical Trial

BackgroundEvidence suggests that the gut microbiota and cardiometabolic status are associated, suggesting dietary interventions that alter the microbiota may affect metabolic health. ObjectivesWe investigated whether supplementation with (poly)phenol-dense red raspberries (RRB), alone or with a fructo-oligosaccharide (FOS) prebiotic, would improve biomarkers of cardiometabolic risk in individuals with prediabetes (PreDM) and insulin resistance (IR) and whether the effects are related to modulation of the gut microbiota. MethodsAdults with PreDM-IR (n = 26; mean ± SEM age, 35 ± 2 years; fasting glucose, 5.7 ± 0.1 mmol/L; HOMA-IR, 3.3 ± 0.3) or who were metabolically healthy (reference group; n = 10; age, 31 ± 3 years; fasting glucose, 5.1 ± 0.2 mmol/L; HOMA-IR, 1.1 ± 0.1) participated in a randomized crossover trial with two 4-week supplementation periods, in which they consumed either RRB (125 g fresh equivalents) daily or RRB + 8g FOS daily, separated by a 4-week washout. The primary outcome variable was the change in the gut microbiota composition, assessed by shotgun sequencing before (baseline) and at the end of each supplementation period. Secondary outcomes were changes in glucoregulation, lipid metabolism, anti-inflammatory status, and anthropometry. The trial is registered at ClinicalTrials.gov, NCT03049631. ResultsIn PreDM-IR, RRB supplementation reduced hepatic-IR (−30.1% ± 14.6%; P = 0.04) and reduced plasma total and LDL cholesterol [−4.9% ± 1.8% (P = 0.04) and −7.2% ± 2.3% (P = 0.003), respectively] from baseline. Adding FOS (RRB + FOS) improved β-cell function [insulin secretion rate, +70.2% ± 32.8% (P = 0.02); Disposition Index, +94.4% ± 50.2% (P = 0.04)], but had no significant effect on plasma cholesterol compared to baseline. RRB increased Eubacterium eligens (2-fold) and decreased Ruminococcus gnavus (−60% ± 34%), whereas RRB + FOS increased Bifidobacterium spp. (4-fold) and decreased Blautia wexlerae (−23% ± 12%) from baseline (all P values ≤ 0.05). R. gnavus was positively correlated with hepatic-IR, and E. eligens and Bifidobacterium catenulatum were negatively correlated with cholesterol concentrations (P ≤ 0.05). ConclusionsIncreased Bifidobacterium spp., concurrently with reduced R. gnavus, was associated with metabolic improvements in adults with PreDM-IR, warranting further research on the mechanisms involved in (poly)phenol/FOS-microbial interactions with host metabolism.

Introduction of adult cats to indirect calorimetry respiration chambers causes increased energy expenditure and respiratory quotient that decrease following acclimation.

To replicate a previously defined behavioral procedure to acclimate adult cats to temporary restriction in indirect calorimetry chambers and measure energy expenditure and respiratory quotient changes during acclimation. 8 healthy adult cats (4 spayed females, and 4 neutered males; mean ± SEM age, 2.5 ± 1.5 years; mean body weight, 4.8 ± 1.8 kg). Cats underwent a 13-week incremental acclimation procedure whereby cats were acclimated to the chambers in their home environment (weeks 1 to 3), to the study room (weeks 4 to 6), and to increasing lengths of restriction within their home environment (weeks 7 to 8) and the chambers (weeks 9 to 13). Cat stress score, respiratory rate, fearfulness (assessed with a novel object test), energy expenditure, and respiratory quotient were measured. Data were analyzed by use of a repeated-measures mixed model. Stress, based on cat stress scores, fearfulness, and respiration, peaked at weeks 4, 9, and 10 but returned to baseline levels by week 11. Energy expenditure and respiratory quotient peaked at weeks 10 and 11, respectively, but were reduced significantly by weeks 11 and 13, respectively. All cats returned to baseline by the end of the study and were deemed fully acclimated. Changes in perceived stress level, energy expenditure, and respiratory quotient at various stages of the acclimation procedure suggest that stress should be considered a significant variable in energy balance measurements when indirect calorimetry is used in cats. An incremental acclimation procedure should therefore be used to prepare cats for the temporary space restriction necessary for indirect calorimetry studies.

Predictive Equations Overestimate Resting Metabolic Rate in Survivors of Chronic Stroke

ObjectiveTo measure resting metabolic rate (RMR) in survivors of chronic (>3 months prior) stroke (mean ± SEM age, 61±7.5 years) and to compare to predicted RMR using predictive equations in adults without stroke. DesignCross-sectional study. SettingHospital. ParticipantsSurvivors of stroke (N=71). InterventionNot applicable. Main Outcome MeasuresRMR was measured by indirect calorimetry. Participants underwent a total body dual-energy x-ray absorptiometry scan and treadmill test for peak oxygen consumption (V̇o2peak). RMR was calculated using 9 established equations. ResultsRMR measured (1552±319 kcal/d) was significantly lower than 9 predicted RMR values (all P<.001), with the best being McArdle-Katch (1652±233 kcal/d), Livingston (1677±230 kcal/d), and Mifflin (1707±242 kcal/d). The Institute of Medicine of the National Academies (2437±386 kcal/d) had the largest discrepancy with measured RMR. Predicted RMR determined with 8 of 9 equations was between 9% and 18% greater than measured RMR. Appendicular lean mass (r=0.64, P<.001), total lean mass (r=0.64, P<.001), and V̇o2peak (r=0.41, P<.001) were associated with measured RMR. ConclusionsRMR predictive equations established in adults without stroke are not appropriate for the population with stroke population, indicating the need to measure RMR until a more accurate predictive equation is developed. This could support modifications to nutritional intake guidelines in patients with conditions of muscle atrophy. If measurement of RMR is not feasible, the Katch-McArdle equation should be used to estimate RMR in a patient with stroke because on average it provides the lowest percentage overestimate compared with other equations.

Evaluation of free light chains of immunoglobulins in normal and pathological seminal fluids: Preliminary data.

Immunoglobulins free light chains (FLCs) are assayable in several biological fluids. Currently, there are no reports on FLCs in seminal plasma. The aims of our study were to investigate the presence and detectability of FLCs in seminal plasma and to evaluate the usefulness of this assay in the diagnostic approach to infertile patients. We enrolled 61 patients aged 18-50years. Semen analysis was performed. They were divided into four groups: controls-normozoospermic, 10 patients, mean±SEM age 35±1.5years; varicoceles (VAR), 18 patients aged 24.3±0.96years; inflammatory (INF) seminal fluids, 24 patients, aged 38.8±2.2years; and varicoceles and inflammatory (VAR/INF) seminal fluids, 9 patients, aged 29.5±0.71years. A trend towards higher λ FLCs levels was evidenced in the INF and VAR/INF groups. κ FLCs were higher in normozoospermic patients with lower levels in VAR, both isolated and associated with inflammatory parameters. This differential pattern of the two types of FLCs reached statistical significance when comparing κ/λ ratio, with significant lower levels in VAR vs controls. This is the first report of FLCs assay in seminal plasma. We can hypothesize that λ FLCs are increased in inflammatory processes, whether κ FLCs seem to be influenced by other molecular mechanisms related to varicocele.

The Goldilocks Procedure with and without Implant-Based Immediate Breast Reconstruction in Obese Patients: The Mayo Clinic Experience.

Obesity is a risk factor for complications in breast reconstruction. Thus, implant-based immediate breast reconstruction in obese women may be controversial. The authors analyzed obese patients who underwent skin-sparing mastectomy using Wise-pattern incisions (Goldilocks procedure) and compared outcomes between two groups: Goldilocks with immediate breast reconstruction and Goldilocks only. A retrospective review was performed of patients with a body mass index of 30 kg/m2 or higher who underwent the Goldilocks procedure at the Mayo Clinic Health System from 2012 to 2019. Data were extracted from electronic medical records. Minor complications (partial-thickness wound dehiscence or flap necrosis, or tissue expander/implant malposition) and major complications (full-thickness wound dehiscence or flap necrosis, capsular contracture, tissue expander/implant explantation, or unplanned reoperation or readmission) were compared between groups. Patient-reported outcomes using BREAST-Q questionnaires were also assessed. One hundred five patients (181 breasts) were included. Mean ± SEM age and body mass index were 57.1 ± 10.4 years and 37.9 ± 5.8 kg/m2 for the Goldilocks-only group and 51.5 ± 1.1 years and 35.5 ± 0.4 kg/m2 for the Goldilocks with immediate breast reconstruction group, respectively. Median follow-up time was 15.1 months (interquartile range, 10.0 to 28.6 months). Overall, 96 breasts underwent the Goldilocks-only procedure and 85 Goldilocks with immediate breast reconstruction. Multivariable analyses revealed a higher rate of minor complications (adjusted hazard ratio, 2.83; 95 percent CI, 1.22 to 7.02) and major complications (adjusted hazard ratio, 2.26; 95 percent CI, 1.25 to 4.24) in the Goldilocks with immediate breast reconstruction group compared with the Goldilocks-only group, at any given time. Patient satisfaction was not statistically different between groups. The Goldilocks procedure is a feasible breast reconstructive option in obese patients; however, when it is performed with immediate breast reconstruction, it is associated with higher rates of complications. For patients with a body mass index of 40 kg/m2 or greater, the authors recommend the Goldilocks-only procedure or delayed reconstruction. Therapeutic, III.

Dietary supplementation with fish oil and safflower oil, during the finishing period, alters brisket muscle fatty acid profile and n-6/n-3 ratio but not carcass traits of dairy beef bulls

With increases in the global population, there is a need to identify strategies that increase beef output while maintaining or improving health benefits of beef products. Studies have demonstrated that there are many benefits to human health in response to reducing the dietary ratio of n-6 to n-3. The aim of this study was to characterize the carcass characteristics and brisket muscle fatty acid profile of young dairy-bred bulls following dietary supplementation with n-6 or n-3 PUFA. Holstein-Friesian (n = 43) and Jersey (n = 7) bulls with a mean ± SEM age and BW of 420.1 ± 5.86 d and 382.0 ± 8.94 kg, respectively, were offered a cereal-based concentrate diet on an ad libitum basis, fortified with 1 of 3 lipid supplements: control (CTL; no supplementary lipid), n-6 PUFA safflower oil (SO), or n-3 PUFA enriched fish oil (FO). Bulls were individually offered their respective diet for 12 wk before slaughter. Carcass weight, conformation, and fat score were recorded at slaughter for all animals. Brisket muscle was collected from 26 randomly selected bulls, and lipid profile was analyzed using gas chromatography. Total n-3 PUFA concentration was greater for FO than for either SO or CTL diets ( P < 0.05). Although there was no difference in the muscle total n-6 concentration between diets ( P = 0.52), the ratio of n-6 to n-3 was 3.2 and 3.9 times lower for FO ( P < 0.001) than either CTL or SO diets, respectively. Total intake of n-3 PUFA accounted for 72% of the variation in the ratio of n-6 to n-3. Despite the differences in fatty acid profiles, there was no effect of dietary lipid supplementation on carcass weight ( P = 0.63), conformation ( P = 0.79), or fat score ( P = 0.84). Beef producers can feed diets enriched with n-6 and n-3 PUFA, which would result in beef having potential health benefits and greater branding potential.

Daily apple consumption reduces plasma and peripheral blood mononuclear cell–secreted inflammatory biomarkers in adults with overweight and obesity: a 6-week randomized, controlled, parallel-arm trial

Obesity-associated low-grade inflammation contributes to the development of cardiovascular disease (CVD). Apples are rich in anti-inflammatory bioactives including polyphenols and fiber. We aimed to determine the effects of regular apple consumption on fasting plasma biomarkers of inflammation (primary outcome), endotoxemia, carbohydrate and lipid metabolism (glucose, insulin, triacylglycerol; secondary outcomes), and peripheral blood mononuclear cell (PBMC)-secreted cytokines (secondary outcome) in individuals with overweight and obesity. A randomized, controlled, parallel-arm trial was conducted with n=46 participants. After avoiding foods and beverages rich in polyphenols and fiber for 2 wk, participants consumed 3 whole Gala apples (∼200 g edible parts)/d as part of their habitual diet (n=23) or avoided apples (control, n=23) for 6 wk. All participants limited consumption of polyphenols and fiber during the 6-wk trial. Fasting blood samples were collected before and after 6 wk for analysis of plasma biomarkers and isolation of PBMCs, which were cultured for 24 h unstimulated or stimulated with LPS (10 ng/mL). Forty-four participants completed the trial (30 female, 14 male; mean±SEM age: 45.4±2.2 y; BMI: 33.4±0.9 kg/m2). After ANCOVA and correcting for multiple comparisons, apples decreased fasting plasma C-reactive protein by 17.0% (range: 14.3%-19.6%, P=0.005), IL-6 by 12.4% (range: 6.7%-17.5%, P<0.001), and LPS-binding protein by 20.7% (range: 14.1%-26.4%, P<0.001) compared with control. Apples also decreased PBMC-secreted IL-6 by 28.3% (range: 22.4%-33.5%, P<0.001) and IL-17 by 11.0% (range 5.8-15.6%, P=0.003) in the unstimulated condition compared with control. Exploratory analysis showed apples also increased plasma total antioxidant capacity by 9.6% (range: 1.7-18.9%, P=0.002) compared with control. However, apples had no effect on anthropometric or other CVD risk markers. Six-week daily whole Gala apple consumption may be an effective dietary strategy to mitigate the obesity-associated inflammation that exacerbates CVD risk, without weight loss. This trial was registered at clinicaltrials.gov as NCT03523403.

Strawberry Consumption, Cardiometabolic Risk Factors, and Vascular Function: A Randomized Controlled Trial in Adults with Moderate Hypercholesterolemia.

Certain fruits, such as strawberries, may impart cardiometabolic benefits due to their phytochemical content. Study aims were to assess the effects of strawberry intake on cardiometabolic risk factors and vascular endothelial function in adults with moderate hypercholesterolemia. This study was a randomized, controlled, double-blinded, 2-arm, 2-period (4-wk/period) crossover trial. Adults (n=34; male/female 1:1; mean±SEM age, 53±1y; BMI, 31±1kg/m2; LDL cholesterol, 133±3mg/dL)were randomly allocated to 1 of 2 study sequences in a 1:1 ratio. Participants drank study beverages twice daily containing freeze-dried strawberry powder (2× 25 g)orenergy-, volume-matched control powder for 4 wk separated by a 4-wk washout. The primary outcome variable was the difference in fasting LDL cholesterol after 4-wk interventions. Secondary outcomes were metabolic markers, inflammation, quantitative (poly)phenolic metabolomics, flow-mediated dilation (FMD), and blood pressure (BP), with the latter (FMD, BP) also assessed acutely at 1h and 2h after a 50-gbolus strawberry or control beverage. Mixed-model analysis of repeated measures via PROC MIXED, PC-SAS was performed on primary and secondary outcome variables. LDL cholesterol did not differ after the 4-wk interventions (P>0.05), nor did fasting total cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, FMD, or BP (all P >0.05). Significant intervention-by-hour interaction for FMD (P=0.03) and BP (P=0.05) revealed increased FMD at 1h after strawberry compared with control by 1.5±0.38%(P=0.0008) and attenuated systolic BP at 2h by 3.1±0.99mmHg(P=0.02). Select phenolic metabolites increased significantly (P<0.05) in blood following strawberry consumption while others decreased, including 3-(4-methoxyphenyl)propanoic acid-3-O-glucuronide, which was significantly correlated with increased FMD (P<0.05). Strawberries may improve vascular health, independent of other metabolic changes. The effect may be related to changes in microbial-derived phenolic metabolites after strawberry consumption influencing endothelial function. Data support inclusion of strawberries in a heart-healthy diet in adults with moderate hypercholesterolemia.This trial was registered at clinicaltrials.gov as NCT02612090.

Postprandial Fatty Acid Profile, but Not Cardiometabolic Risk Markers, Is Modulated by Dairy Fat Manipulation in Adults with Moderate Cardiovascular Disease Risk: The Randomized Controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) Study.

ABSTRACTBackgroundChronic consumption of dairy products with an SFA-reduced, MUFA-enriched content was shown to impact favorably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation.ObjectiveThe effects of sequential high-fat mixed meals rich in fatty acid (FA)–modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above the population mean) were compared.MethodsIn a randomized crossover trial, 52 participants [mean ± SEM age: 53 ± 2 y; BMI (kg/m2) 25.9 ± 0.5] consumed a high-dairy-fat breakfast (0 min; ∼50 g total fat: modified: 25 g SFAs, 20 g MUFAs; control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ∼30 g total fat; modified: 15 g SFAs, 12 g MUFAs; control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300, and 420 min. Data were analyzed by linear mixed models.ResultsPostprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher AUC for the %FMD response following the modified-dairy-fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans-18:1, respectively, following the modified relative to the control dairy meals (all P < 0.0001).ConclusionsIn adults at moderate cardiovascular risk, acute consumption of sequential high-fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals.This trial was registered at clinicaltrials.gov as NCT02089035.

Co-administration of viscous fiber, Salba-chia and ginseng on glycemic management in type 2 diabetes: a double-blind randomized controlled trial

Viscous dietary fiber, functional seeds and ginseng roots have individually been proposed for the management of diabetes. We explored whether their co-administration would improve glycemic control in type 2 diabetes beyond conventional therapy. In a randomized, double-blind, controlled trial conducted at two academic centers (Toronto, Canada and Zagreb, Croatia), individuals with type 2 diabetes were assigned to either an active intervention (10g viscous fiber, 60g white chia seeds, 1.5g American and 0.75g Korean red ginseng extracts), or energy and fiber-matched control (53g oat bran, 25g inulin, 25g maltodextrose and 2.25g wheat bran) intervention for 24weeks, while on conventional standard of care. The prespecified primary endpoint was end difference at week 24 in HbA1c, following an intent-to-treat analysis adjusted for center and baseline. Between January 2016 and April 2018, 104 participants (60M:44F; mean ± SEM age 59 ± 0.8 years; BMI 29.0 ± 0.4kg/m2; HbA1c 7.0 ± 0.6%) managed with antihyperglycemic agent(s) (n = 98) or lifestyle (n = 6), were randomized (n = 52 test; n = 52 control). At week 24, HbA1c levels were 0.27 ± 0.1% lower on test compared to control (p = 0.03). There was a tendency towards an interaction by baseline HbA1c (p = 0.07), in which a greater reduction was seen in participants with baseline HbA1c > 7% vs ≤ 7% (- 0.56 ± 0.2% vs 0.03 ± 0.2%). Diet and body weight remained unchanged. The interventions were well tolerated with no related adverse events and with high retention rate of 84%. Co-administration of selected dietary and herbal therapies was well-tolerated and may provide greater glycemic control as add-on therapy in type 2 diabetes. Registration: Clinicaltrials.gov NCT02553382 (registered on September 17, 2015).

Adults Who Are Overweight or Obese and Consuming an Energy-Restricted Healthy US-Style Eating Pattern at Either the Recommended or a Higher Protein Quantity Perceive a Shift from “Poor” to “Good” Sleep: A Randomized Controlled Trial

Limited evidence suggests that consuming a higher-protein diet during weight loss improves subjective indices of sleep in overweight and obese adults. We sought to a priori assess the effects of consuming the recommended versus a higher protein Healthy US-Style Eating Pattern during energy-restriction on sleep quality indices. Using a randomized, parallel study design, 51 adults (mean±SEM age: 47±1 y; BMI: 32.6±0.5kg/m2) consumed a controlled USDA Healthy US-Style Eating Pattern containing 750kcal/d less than their estimated energy requirement for 12 wk. Participants were randomly assigned to consume either 5 or 12.5 oz-equivalent (eq)/d of protein foods. The additional 7.5 oz-eq/d came from animal-based protein sources and displaced primarily grains. Objective (wrist-worn actigraphy) and subjective (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale) sleep quality indices were measured at baseline, week 6, and week 12. Among all participants, body mass decreased (-6.2±0.4kg). Dietary protein intake did not affect any objective or subjective sleep quality outcomes measured (repeated measures ANOVA). Over time, objective measures of time spent in bed, time spent sleeping, sleep onset latency, and time awake after sleep onset did not change; however, sleep efficiency improved (1±1%; P=0.027). Subjectively, global sleep scores [GSS: -2.7±0.4 arbitrary units (au)] and daytime sleepiness scores (-3.8±0.4 au; both P < 0.001) improved over time. The GSS improvement transitioned the participants from being categorized with "poor" to "good" sleep (GSS: >5 compared with ≤5 au of a 0-21 au scale; baseline 7.6±0.4 au, week 12: 4.8±0.4 au). Although objective sleep quality may not improve, adults who are overweight or obese and poor sleepers may become good sleepers while consuming either the recommended or a higher-protein energy-restricted Healthy US-Style Eating Pattern. This trial was registered at clinicaltrials.gov as NCT03174769.

Abstract 13215: Gender-affirming Hormones Are Associated With Increased Risk of QT Prolongation in Transgender Females

Introduction: Women have a longer QT interval than men. This sex-specific difference is attributed to hormones associated with the biological female sex. Male-to-female transgender individuals often take antiandrogens such as spironolactone or goserelin in addition to estrogens to suppress testosterone effects while increasing feminine features. Effects of gender-affirming hormone therapy (GHT) on the QT interval in these individuals remains to be elucidated. Hypothesis: We assessed the hypothesis that the use of GHT is associated with an increased risk for QT interval prolongation in transgender females. Methods: We identified 46 transgender females through a search of the electronic medical records of a Veterans Administration hospital in Northern Nevada. Patients with a diagnosis of congenital long QT syndrome were excluded. Of these, 13 patients had ECGs before and after initiation of GHT and were included. We adapted the Tisdale score using the auto-calculated corrected QT interval (QTc) to estimate the risk of QT prolongation. Age, QTc, and Tisdale scores before and after GHT initiation were compared using the Wilcoxon signed-rank test. All tests were performed as two-tailed at a 5% level of significance. Results: All 13 study patients were taking estrogens. Of these, 3 (23.1%) were taking goserelin and 9 (69.2%) were taking spironolactone. Mean ± SEM age at ECG acquisition was 45.0 ± 4.4 and 47.7 ± 4.7 years before and after the initiation of GHT respectively. Mean ± SEM QTc after initiation of GHT was significantly higher compared to the baseline (467.5 ± 12.8 ms vs. 428.2 ± 7.1 ms) (Figure 1A). The average baseline Tisdale score was significantly smaller on follow-up (1-point vs. 3 points) (Figure 1B). Conclusions: GHT appears to be associated with increased QTc in transgender women. This needs to be interpreted with caution owing to the very small sample size in this study. Further studies to investigate the strength of this association, if it exists, are warranted.

High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males

Unavoidable periods of disuse lead to muscle atrophy and functional decline. Preventing such declines can reduce the risk of re-injury and improve recovery of normal physiological functioning. We aimed to determine the effectiveness of high-dose leucine supplementation on muscle morphology and strength during 7 d of unilateral lower-limb immobilization, and the role of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in disuse atrophy. Sixteen healthy males (mean±SEM age: 23±1 y) underwent 7 d of unilateral lower-limb immobilization, with thrice-daily leucine (LEU; n=8) or placebo (PLA; n=8) supplementation (15 g/d). Before and after immobilization, muscle strength and compartmental tissue composition were assessed. A primed continuous infusion of l-[ring-13C6]-phenylalanine with serial muscle biopsies was used to determine postabsorptive and postprandial (20 g milk protein) MyoPS and MitoPS, fiber morphology, markers of protein turnover, and mitochondrial function between the control leg (CTL) and the immobilized leg (IMB). Leg fat-free mass was reduced in IMB (mean±SEM: -3.6%±0.5%; P=0.030) but not CTL with no difference between supplementation groups. Isometric knee extensor strength declined to a greater extent in IMB (-27.9%±4.4%) than in CTL (-14.3%±4.4%; P=0.043) with no difference between groups. In response to 20 g milk protein, postprandial MyoPS rates were significantly lower in IMB than in CTL (-22%±4%; P<0.01) in both LEU and PLA. Postabsorptive MyoPS rates did not differ between legs or groups. Postabsorptive MitoPS rates were significantly lower in IMB than in CTL (-14%±5%; P<0.01) and postprandial MitoPS rates significantly declined in response to 20 g milk protein ingestion (CTL: -10%±8%; IMB: -15%±10%; P=0.039), with no differences between legs or groups. There were no significant differences in measures of mitochondrial respiration between legs, but peroxisome proliferator-activated receptor γ coactivator 1-α and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P<0.05), with no differences between groups. High-dose leucine supplementation (15 g/d) does not appear to attenuate any functional declines associated with 7 d of limb immobilization in young, healthy males.This trial was registered at clinicaltrials.gov as NCT03762278.

MON-280 Plasmatic Lipocalin-2 Levels in Chronic Low-Grade Inflammation Syndromes: Comparison Between Metabolic Syndrome, Total and Partial Growth Hormone Deficiency

Lipocalin-2 (LCN2) is a secreted glycoprotein, member of the lipocalin superfamily and mediator of several chronic inflammatory processes. Metabolic syndrome (METs) and total growth hormone deficiency (GHD) are known as chronic inflammatory conditions (1,2). While discrepant results have been found in literature on LCN2 plasmatic levels in metabolic syndrome, no studies have been performed in GHD. Partial growth hormone deficiency (pGHD) either is associated with cardiovascular risk (3). Therefore, the primary end-point of this observational cross-sectional study was to compare LCN2 in these clinical settings, trying to assess its possible role as a biomarker in these diseases, whether the secondary end-point was to evaluate the impact of BMI and indexes of insulin sensitivity/resistance on this protein plasmatic levels. 74 patients were included in the study. They were divided as follows: Group A, METs (18 patients, 13 females and 5 males, mean±SEM age 45.1±4.11 ys, BMI 31.22±1.73 kg/m2); Group B, GHD (18 patients, 8 F and 10 M, mean±SEM age 52.44±2.61 ys, BMI 30.49±1.87 kg/m2); Group C, Partial GHD (19 patients, 13 F and 6 M, mean±SEM age 48.63±2.19 ys, BMI 29.11±1.85 kg/m2); Group D, Controls (19 patients, 13 F and 6 M, mean±SEM age 40.26±2.87 ys, BMI 23.25±0.95 kg/m2). The diagnosis of metabolic syndrome was made according to NCEP ATPIII criteria (2005 revision). GHD was diagnosed with dynamic test using Growth Hormone-Releasing Hormone (GHRH 50 μg i.v. + arginine 0,5 g/Kg), with a peak GH response between 9 and 16 μg/L when BMI was < 30 kg/m2 or 4 and 9 μg/L when BMI was > 30 kg/m2. Partial GHD was defined with dynamic test using GHRH, with a peak GH response < 9 μg/L when BMI was < 30 kg/m2 or < 4 μg/L when BMI was > 30 kg/m2.They were evaluated for: serum glucose and insulin, HOMA-index, QUICKI-index, Total/LDL/HDL cholesterol, triglycerides, IGF-1 and LCN2 (measured using ELISA kit DuoSet LCN2/NGAL, R&D systems).LCN2 plasmatic levels were significantly increased in METs, while no difference with control group was found in total and partial GHD. LCN2 levels were not influenced by BMI and HOMA-index. A significant positive correlation between LCN2 and HOMA-index was found in controls, while a trend-like, yet not significant, positive correlation was evidenced in partial GHD. No correlations between these parameters were identified in METs and GHD groups. Our data support the hypothesis that LCN2 plasmatic levels increase in metabolic syndrome. As previously shown (4), different inflammatory patterns characterize the two pathological conditions. However, the correlation between HOMA index and LCN2 suggest a possible modulatory action of LCN2 on insulin resistance in normal subjects and partial GHD ones. (1): Esser et al, Diab Res Clin Prac, 105(2):141–50, 2014.(2): Caicedo et al, Int J Mol Sci, 19(1), 2018.(3): Colao et al, JCEM, 91(6):2191–200, 2006.(4): Mancini et al, Endocrine, 59(1):130–136, 2018.