Fat Pad Research Articles

Abstract 2007: Ischemic And Non-ischemic Cardiovascular Events Differentially Regulate Cross Disease Communication With Cancer

Cancer and cardiovascular disease (CVD) are the top two leading causes of death worldwide, exhibiting cross-disease communication that increases morbidity. Cancer patients are at significantly increased risk for CVD and recent studies by our lab and others indicate that CVDs like myocardial infarction (MI) or heart failure can in turn accelerate tumor growth. We previously showed this occurs through changes in the innate immune system or via tumor-promoting factors secreted from the damaged myocardium, which together have established the nascent field of Reverse CardioOncology. We hypothesized that ischemic and non-ischemic CVD injuries have distinctly different mechanisms underlying mammary tumor growth. To mimic these events, we modeled non-cardiac hind limb ischemic injury by femoral artery ligation (FAL) and non-ischemic cardiac injury by cardiac cryoinjury (CCI). To test our hypothesis, we introduced primary E0771 mouse mammary cancer cells into the mammary fat pad three days prior to FAL or CCI. Measurements of tumor over time showed significant increases in tumor growth after both FAL and CCI when compared to sham surgeries. However, only the ischemic injury, FAL, induced similar changes in immune cells to what we observed after MI (induced by left anterior descending coronary artery [LAD] ligation). This included significant increases in myeloid populations and decreased lymphocytes within the circulation. Additionally, flow cytometry of immune cells within tumors of mice exposed to FAL showed significantly increased myeloid cells and macrophages, as well as increased immunosuppressive T-regulatory cells. In contrast, while CCI showed significantly increased tumor burden and circulating leukocytes, there were no differences in the above-mentioned subsets of immune cells within the circulation or within the tumor. These data suggest that ischemic injury, via FAL or LAD, induces an immunosuppressive environment within the tumor that accelerates cancer growth that is distinct from the non-ischemic cardiac injury induced by CCI. Taken together, our data suggest that the immune reprogramming after ischemic CVDs is a risk factor for tumor growth and these data help to elucidate the mechanisms that underlie cancer risk in CVD patients.

The role of the cardiac vagus in maintaining cardiac function during exercise

There is a strong association between parasympathetic nervous system activity (vagal tone) and physical fitness. High vagal tone is associated with increased capacity to exercise and overall cardiovascular health. Evidence for vagal withdrawal during exercise comes from historic studies examining heart rate control and the use of cholinergic blockers. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via neurotransmitters other than acetylcholine. The left cardiac vagal branch was identified in anesthetized open-chested sheep. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Custom-built coil electrodes were placed around the left cardiac vagal branch. 3-10 days after surgery, conscious, direct recordings of cardiac vagal nerve activity (CVNA), cardiac output, coronary artery blood flow and heart rate were recorded in adult female sheep during whole-body treadmill exercise. Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), vasoactive intestinal peptide (VIP) ([4Cl−D-Phe6,Leu17]-VIP 25 μg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated. Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded CVNA increased during exercise. CVNA increases during the lowest exercise intensity and plateaus as exercise intensity increases. Left cardiac vagal branch, denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5 ± 5.9 ml/min, n = 8, cardiac vagal denervated: 32.7 ± 5.6 ml/min, n = 6, mean ± SEM. P = 2.5x10−7. Two-way ANOVA-interaction), cardiac output and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation (maximum exercise, paired: control: 68.2 ± 6.0 ml/min, VIP antagonism: 44.9 ± 3.9 ml/min, n = 6, mean ± SEM. P = 4.8x10−3. Two-way ANOVA-interaction). Our study challenges the conventional view and demonstrates that cardiac vagal nerve activity increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show that the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP and that acetylcholine has no role in modulating cardiac function during exercise. This work is supported by the Health Research Council of New Zealand 23/119 (Fellowship. JS) and the New Zealand Heart Foundation (JS, RR). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Defining healthy and breast tumor-associated neutrophils at a whole-organism, single-cell resolution

Abstract Neutrophils accumulate systemically in tumor-bearing organisms, and have been shown to promote primary tumor progression and metastasis through suppression of the anti-tumor immune response. However, neutrophils have specialized phenotypes in different organs, and their full transcriptional heterogeneity and maturation trajectory has yet to be defined across healthy and cancer states. Here, we performed single-cell RNA sequencing on isolated neutrophils from bone marrow, spleen, lymph nodes, blood, mammary fat pad/tumor, and lungs from wild-type and breast tumor-bearing MMTV-PyMT mice. Our analysis reveals distinct transcriptional programs which distinguish systemic neutrophil function in normal homeostasis and cancer. In wild-type mice, we describe a neutrophil maturation trajectory that begins with granulopoiesis in the bone marrow, continues development in the spleen and blood, and reaches a fully mature state in the lymph nodes, mammary fat pad, and lungs. This is captured by five maturation stages, N0-N4, each with its own characteristic gene signature. In MMTV-PyMT mice, we observe a systemic upregulation of genes including Ifitm1, Wfdc17, Clec4e, Igfbp6, and Saac, which have been implicated in cancer-induced immunosuppression. Taken altogether, this work provides a multi-organ perspective into neutrophil development across healthy and cancer states and identifies markers specific to breast tumor-associated neutrophils which may be potential immunotherapeutic targets.

Correction of severe upper-eyelid sunken deformity in Asians by double-eyelid procedure and combination of orbital fat pad repositioning and autologous fat transplantation: a one-year follow-up study of 79 cases.

Nowadays, people's pace of life continues to rapid up, and many bad habits will accelerate the aging of the eye periphery, and patients with sunken upper eyelids are to be found in younger people. In young Asians, single eyelids are often accompanied by upper eyelid depression, so correcting the upper eyelid depression during blepharoplasty becomes a higher challenge for plastic surgeons. Current surgical methods for upper eyelid depression include three major categories: tissue repositioning, injection and filling, and combined use. According to grades 1 and 2 are mild or moderate upper eyelid sunken. The sunken can be well corrected only by repositioning the orbital fat pad, while the correction effect for severe upper eyelid sunken in grades 3 and 4 is Poor, need to be used in combination to achieve the desired effect. The authors sought to determine whether, for patients with single eyelids and severe upper eyelid depression of grades 3 and 4, combined with orbital fat pad repositioning and autologous fat transplantation during blepharoplasty, an aesthetic and youthful blepharoplasty can be achieved. This study included 79 patients with single eyelids and severe upper eyelid depression of grades 3 and 4 who received treatment between June 2020 and July 2022. All patients underwent double eyelid surgery plus orbital fat repositioning and autologous fat grafting. After a minimum follow-up period of 1 year, overall patient satisfaction was 92%. The recurrence rate within the first year was 6% and the complication rate was 5%. This combined surgery may be an option for young Asians with single eyelids and severe upper eyelid depression. In this study, the surgery resulted in natural-looking double eyelids and younger-looking eye sockets in most patients. A combination of different surgical methods based on the patient's preoperative condition is critical to achieving long-term correction.

Association between quadriceps fat pad edema and patellofemoral osteoarthritis: a quantitative Q-Dixon-based magnetic resonance imaging (MRI) analysis.

Anterior knee pain (AKP) is a common symptom of patellofemoral osteoarthritis (PFOA). There is limited prospective evidence supporting the relationships between patellofemoral maltracking parameters, AKP, and PFOA. Thus, this prospective cross-sectional study aimed to determine the association between quadriceps fat pad (QFP) edema and patellofemoral maltracking in patients with chronic AKP and to evaluate the feasibility and diagnostic performance of a PFOA assessment using fat fraction (FF) and T2* based on Q-Dixon. This was a cross-sectional study with prospective data collection. Patients with chronic AKP were recruited from an orthopedic outpatient magnetic resonance imaging (MRI) waiting room at Shanghai Tongren Hospital between November 1, 2022, and April, 30, 2023. Exclusion criteria included age of <18 years, knee trauma, major internal derangement, prior surgery/arthroscopy, pre-existing joint diseases, and contraindications to MRI. MRI was performed using a 3.0-T instrument, and patellofemoral maltracking parameters were measured. Patellofemoral feature-relevant items, including patellar cartilage defects, patellar bone marrow lesions (BMLs), patellar osteophytes, anterior femoral osteophytes, Hoffa synovitis, and synovitis-effusion, from the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) were measured. The Anterior Knee Pain Scale (AKPS) was used to assess pain and function. FF/T2* measurement differences between groups and their associations with maltracking metrics, osteoarthritis grading based on the Iwano grading system, MOAKS, and AKPS, were investigated. Based on Iwano grading, the participants were categorized as having no-PFOA (n=40), mild PFOA (n=40), and advanced PFOA (n=40). Chi-squared and one-way analysis of variance were used to assess potential differences between the groups. Spearman's correlation test was used to analyze the correlation between the morphological parameters, AKPS, Iwano grade, MOAKS, and MRI quantitative values. Receiver operating characteristic (ROC) curves assessed the area under the curve (AUC), sensitivity, and specificity of quantitative values for distinguishing PFOA from no-PFOA. Among the 120 included patients, those in the mild (86.2±8.5) and advanced (83.9±9.5) PFOA groups had significantly lower AKPS scores than those in the no-PFOA group (88.8±7.3) (P=0.03). The mean FF and T2* values of the QFP were significantly higher in the no-PFOA group than those in the mild and advanced PFOA groups (P<0.001 for FF and P=0.02 for T2*). Quantitative data on the QFP and patellofemoral maltracking parameters showed no association. FF (r=-0.686, P<0.001) and T2* (r=-0.314, P=0.008) showed a negative correlation with the Iwano grade. The AUCs for PFOA diagnosis were 0.906 [95% confidence interval (CI), 0.853-0.960] (FF) and 0.744 (95% CI, 0.657-0.831) (T2*). QFP FF and T2* were not associated with patellofemoral maltracking parameters but with increased PFOA in patients with AKP, suggesting that QFP abnormalities play a role in PFOA. Therefore, a quantitative QFP assessment (FF and T2*) based on Q-Dixon technology could be a convenient and reliable new imaging biomarker for PFOA severity during clinical diagnosis, treatment, and follow-up.

Gross anatomy of vascular supply and drainage of mammary fat pads in mice models.

This work extensively studied the vasculature of mice mammary fat pads (BALB/c and C57BL/6) with special reference to haematogenous drainage routes. Mammary fat pads were five pairs (first cervical, second and third thoracic, fourth abdominal and fifth inguinal), bilaterally symmetrical, extending laterally and continuously with the subcutaneous fascia. The superficial cervical artery and vein primarily accomplished the blood vasculature of the first mammary fat pad, while the lateral thoracic and external thoracic arteries and veins supplied the second and third mammary fat pads. The superficial cervical vein (found parallel to the superficial cervical artery) drained into the external jugular vein. The lateral thoracic artery and external thoracic artery branched almost at the same level as the axillary artery (branch of subclavian artery), the latter being more medial in position. However, in some specimens, the branching of both arteries appeared to be at the same level, and their origins were indistinguishable. The lateral thoracic vein that was parallel to the lateral thoracic artery drained to the axillary vein close to the drainage of the external thoracic vein. The lateral thoracic, superficial caudal epigastric, iliolumbar and external thoracic arteries and veins vascularized the fourth mammary fat pad and displayed anastomosis among themselves. The iliolumbar vein (found parallel to the iliolumbar artery) drained into the inferior vena cava. The superficial caudal epigastric vein (found parallel to the superficial caudal epigastric artery (SCaEA)) drained into the femoral vein. Unlike humans, the internal thoracic artery and vein did not participate in the vasculature of mammary fat pads. The SCaEA and vein supplied blood and drained the fifth mammary fat pad. The anatomical continuity of the fourth and fifth mammary fat pads provided common drainage for both mammary fat pads. The BALB/c and C57BL/6 mice strains studied did not differ in topography and size of mammary fat pads. The vascular supply and drainage of the mammary fat pads also did not differ in the strains studied. Only minor variations could be noted in the small veins draining into the lateral thoracic vein. Lateral tributaries seen in the terminal end of the lateral thoracic vein were absent in the C57BL/6 mice.

Associating Knee Osteoarthritis Progression with Temporal-Regional Graph Convolutional Network Analysis on MR Images.

Artificial intelligence shows promise in assessing knee osteoarthritis (OA) progression on MR images, but faces challenges in accuracy and interpretability. To introduce a temporal-regional graph convolutional network (TRGCN) on MR images to study the association between knee OA progression status and network outcome. Retrospective. 194 OA progressors (mean age, 62 ± 9 years) and 406 controls (mean age, 61 ± 9 years) from the OA Initiative were randomly divided into training (80%) and testing (20%) cohorts. Sagittal 2D IW-TSE-FS (IW) and 3D-DESS-WE (DESS) at 3T. Anatomical subregions of cartilage, subchondral bone, meniscus, and the infrapatellar fat pad at baseline, 12-month, and 24-month were automatically segmented and served as inputs to form compartment-based graphs for a TRGCN model, which containing both regional and temporal information. The performance of models based on (i) clinical variables alone, (ii) radiologist score alone, (iii) combined features (containing i and ii), (iv) composite TRGCN (combining TRGCN, i and ii), (v) radiomics features, (vi) convolutional neural network based on Densenet-169 were compared. DeLong test was performed to compare the areas under the ROC curve (AUC) of all models. Additionally, interpretability analysis was done to evaluate the contributions of individual regions. A P value <0.05 was considered significant. The composite TRGCN outperformed all other models with AUCs of 0.841 (DESS) and 0.856 (IW) in the testing cohort (all P < 0.05). Interpretability analysis highlighted cartilage's importance over other structures (42%-45%), tibiofemoral joint's (TFJ) dominance over patellofemoral joint (PFJ) (58%-67% vs. 12%-37%), and importance scores changes in compartments over time (TFJ vs. PFJ: baseline: 44% vs. 43%, 12-month: 52% vs. 39%, 24-month: 31% vs. 48%). The composite TRGCN, capturing temporal and regional information, demonstrated superior discriminative ability compared with other methods, providing interpretable insights for identifying knee OA progression. Stage 2.

The addition of calcium soap in the ration on the performance, carcass and abdominal fat of native chickens

This study aims to examine the effect of adding calcium soap (Ca-PFAD) to feed on performance, carcass and abdominal fat in native chickens. A total of two hundred and forty 6 week old native chickens were obtained from commercial native chicken farming with an average body weight of 662.52±21.75 g. All chickens were kept in a room with controlled environment. A total of 240 native chickens were divided randomly into four treatments, namely control feed without Ca-PFAD supplement as control (C0); feed supplemented with 2% Ca-PFAD (C1); added feed with 4% Ca-PFAD (C2); and diet supplemented with 6% Ca-PFAD. All diets were isocaloric and isonitrogen. Each treatment had six replications and each replication had 60 chickens. The results showed that the addition of 2-4% Ca-PFAD in feed significantly (P&lt;0.05) improved performance, carcasses, carcass percentage and carcass meat percentage. The amount of pad fat and abdominal fat in chickens decreased significantly (P&lt;0.05) with the addition of 2% Ca-PFAD in the feed. It can be concluded that the addition of 2% calcium soap (Ca-PFAD) in feed can improve performance and carcass quality in native chickens, on the other hand it can reduce the amount of abdominal fat.

A reinterpretation of human breast anatomy includes all the layers of the anterior body wall.

Mammary glands define mammals as a group, yet a comprehensive anatomical description of the mammary gland does not exist for almost any mammalian species. In humans, the anatomical and surgical literature provide conflicting and incomplete descriptions of the gross anatomy of the breast. We dissected 9 male and 15 female human body donors to clarify this gross anatomy. We found that, like other epidermally derived glands of the body, the mammary glandular tissue is constrained to a membrane-bound, central structure referred to as the corpus mammae in the surgical literature, and not dispersed throughout the breast as typically described in the anatomical literature. The major fasciae of the human anterior body wall, including the superficial fatty Camper's fascia and the deeper membranous Scarpa's fascia, both contribute to the structure of the breast. This anatomical arrangement suggests that, as the mammary gland invaginates posteriorly from the integument during embryological development, the mammary fat pad most likely derives from Camper's fascia, and growth of Scarpa's fascia around this fat pad forms the anterior and posterior lamellae of the breast pocket. Anteriorly, Scarpa's fascia becomes a double layer that creates the surface structure of the breast. Posteriorly, Scarpa's fascia forms a circummammary ligament that (1) stabilizes the breast against the thoracic wall and (2) is continuous with Scarpa's fascia on the rest of the anterior body wall. The suspensory ligaments of the breast represent the typical retinaculae cuti found consistently throughout the human body wall, and do not directly attach to the skin. Instead, these retinaculae attach to the anterior or posterior lamella of Scarpa's fascia.

Is bovine somatotropin an alternative strategy to overcome the detrimental effects of high-gain diets on prepubertal Holstein × Gyr heifers?

Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus, frequent application of bovine somatotropin (bST) may prevent future losses in productivity, improve mammary development and animal performance. We aimed to evaluate the effects of bST on digestibility, performance, blood metabolites, mammary gland development, and carcass composition of high-performance prepubertal Holstein × Gyr heifers. Thirty-four Holstein × Gyr heifers with an average initial body weight of 218 ± 49 kg and 14 ± 4 months of age were submitted to an 84-day trial evaluating the effects of no bST or bST injections. Treatments were randomly assigned to each animal within one of the tree blocks. The bST did not influence digestibility or performance parameters. Regarding blood results, IGF1 concentration presented an interaction between treatment and day, where bST heifers had the highest IGF1 concentration. Heifers receiving bST also showed increased ribeye area; however, only an experimental day effect for backfat thickness was observed, with greater accumulation of carcass fat on day 84. Heifers receiving bST had lower pixels/mm² on parenchyma, characteristic of greater parenchymal tissue. Moreover, heifers on bST treatment also had reduced pixels/mm2, characteristic of reduced fat pad tissue. Lastly, bST injections did not influence liver and muscle gene expression, nor most genes evaluated in mammary gland tissue, except for IGFBP3 expression, which was greater for bST heifers. In summary, we confirm the efficacy of bST injections to overcome the detrimental effects of high-gain diets on mammary gland growth and to improve lean carcass gain of prepubertal Holstein × Gyr heifers.

Effect of Low-Intensity Pulsed Ultrasound on Macrophage Properties and Fibrosis in the Infrapatellar Fat Pad in a Carrageenan-Induced Knee Osteoarthritis Rat Model.

In the progression of knee osteoarthritis (KOA), fibrosis of the infrapatellar fat pad (IFP) is a key pathological change. Low-intensity pulsed ultrasound (LIPUS) inhibits IFP fibrosis by decreasing the gene expression and activity of hypoxia-inducible factor (HIF-1α), which is a protein involved in IFP fibrosis in KOA rat models. On the other hand, macrophages play an important role in the progression of fibrosis in various tissues, and LIPUS irradiation suppresses macrophage infiltration and inflammatory cytokine secretion. However, whether LIPUS suppresses macrophage polarity and IFP fibrosis in KOA remains unclear. Therefore, we investigated the effect of LIPUS on macrophage polarity and IFP fibrosis. A KOA model was created by injecting carrageenin into the bilateral knee joints of Wistar rats (eight weeks old). Tissues were harvested over time for histological and molecular biological analysis. The KOA model was also subjected to LIPUS irradiation for two weeks following the injection of carrageenin. RM-4-positive cells were widely distributed in IFP two weeks after carrageenin administration, but M2 macrophages were significantly increased, and the Sirius red area was decreased in the LIPUS-irradiated group compared with those in the non-irradiated group. The gene expression of M1 macrophage markers was significantly decreased and that of M2 macrophage markers was significantly increased in the LIPUS-irradiated group. The expression of transforming growth factor-β (TGF-β) and type 1 collagen was also significantly decreased. These results suggest that LIPUS may serve as a novel approach for the treatment of KOA through its effect on M1 macrophages and suppression of TGF-β expression.

Sonographic Characterization of the Pericruciate Fat Pad with the Use of Compression Elastography-A Cross-Sectional Study among Healthy and Post-Injured Patients.

Background: The pericruciate fat pad (PCFP) in the knee joint is still insufficiently studied despite its potential role in knee pathologies. This is the first reported study which aimed to clarify the characteristics of the PCFP in healthy individuals and contrast them with cases of post-traumatic injuries. Methods: Conducted as a retrospective cross-sectional study (n = 110 knees each) following STROBE guidelines, it employed grayscale ultrasound with echogenicity measurement, compression elastography with elasticity measurement, and Color Doppler for blood flow assessment. Results: PCFP showed a homogenic and hyperechoic echostructure. The echogenicity of the PCFP was higher than that of the posterior cruciate ligament (PCL) (p < 0.001, z-score = 8.97) and of the medial head of gastrocnemius (MHG) (p = 0.007, z-score = 2.72) in healthy knees, but lower than subcutaneous fat (SCF) (p < 0.001, z-score = -6.52). Post-injury/surgery, PCFP echogenicity surpassed other structures (p < 0.001; z-score for PCL 12.2; for MHG 11.65 and for SCF 12.36) and notably exceeded the control group (p < 0.001, z-score = 8.78). PCFP elasticity was lower than MHG and SCF in both groups, with significantly reduced elasticity in post-traumatic knees (ratio SCF/PCFP 15.52 ± 17.87 in case group vs. 2.26 ± 2.4 in control group; p < 0.001; z-score = 9.65). Blood flow was detected in 71% of healthy PCFPs with three main patterns. Conclusions: The main findings, indicating increased echogenicity and reduced elasticity of PCFP post-trauma, potentially related to fat pad fibrosis, suggest potential applications of echogenicity and elasticity measurements in detecting and monitoring diverse knee pathologies. The description of vascularity variations supplying the PCFP adds additional value to the study by emphasizing the clinically important role of PCFP as a bridge for the middle genicular artery on its way to the inside of the knee joint.

Release of fibrous web bands between the preaponeurotic fat pad and Levator aponeurosis in subclinical blepharoptosis correction during double-eyelid blepharoplasty.

Double-eyelid blepharoplasty is a popular cosmetic procedure in Asia; however, there are some drawbacks to this procedure for mild blepharoptosis. Enhancing movement of the levator aponeurosis can correct blepharoptosis through the release of fibrous web bands present between the preaponeurotic fat pad and levator aponeurosis. To improve our understanding of the anatomical link between the levator aponeurosis and orbital septum fat and to introduce that the release of the link can provide favorable results in double-eyelid blepharoplasty. We included patients with latent ptosis or subclinical blepharoptosis who underwent double-eyelid blepharoplasty with the release of fibrous web bands between June 2021 and March 2023. Mild ptosis was corrected following complete release of the fibrous bands beneath the preaponeurotic fat pad. Patients were followed up for 4-12 months postoperatively, and surgical outcomes were evaluated. Patient demographic variables and photographs were collected pre- and postoperatively. Patients, surgeons, and laypersons were asked to evaluate the outcomes postoperatively. The Friedman's nonparametric (for repeated measures) two-way analysis of variance was used for statistical analyses. Outcomes were assessed in 45 individuals with an average monitoring period of 6.9 months. There were no cases of incomplete eyelid closure or upper eyelid ectropion. Over 50% of the surgical outcomes were deemed "satisfactory" by each of the three groups in relation to the widening of the eyelid fissure. Most of the examined patients demonstrated favorable long-term results. Fibrous web bands are implicated in subclinical or mild blepharoptosis. The release of fibrous web bands between the preaponeurotic fat pad and levator aponeurosis can provide favorable results in double-eyelid blepharoplasty.

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation

BackgroundPostoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. ObjectivesThis study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. MethodsThis phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. ResultsAmong 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years of age (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years of age (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. ConclusionsThere were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68)

NOT LOSING ONE CM OF MUSCLE CIRCUMFERENCE DURING EXTENSIVE BONE LENGTHENING: A PACT WITH THE DEVIL OR THE ANGELS?

IntroductionA 6cm femoral gain requires 5-Y during normal growth, but only 6–8-W surgically (x30–40 faster). In lengthening surgery, losses of muscle force (MF) and circumferences (MC) are major. Recovery is long, preventing sports till bone fusion.Can we maintain MC and strength throughout the entire lengthening and how?We monitored for over 30 years patients for muscle force (isokinetic), circumferences, activities (including sports) and food intake, and acted on the 5 principles of the Osteostasis.Materials &amp; MethodsOver 750 femoral lengthening with Full WB Nails (FWBN) got Isokinetic testing (≧1991), circumferences measurements (≧2012; 20-15-10-5-0cm above patella, max-calf, mini/max-ankle), food intake (≧2012), using MyFitnessPal App (≧2016), gradually enforced. Preoperative training along with a daily post-operative training are supervised by our trainers. Recommendations for food intake and activities were provided. Patients noted on a specific App all parameters. Compliance was noted.ResultsInstead of a traditional 7–9cm circumference loss for 8–10cm gains using Ex-fix or nails, with FWBN and our protocols, no MC loss could be noted in compliant pre-trained patients, intensive early post-op resistance training, high calory intake (M:&gt;4200, F:&gt;3000; 20–25% Proteins) and supplements (no fat pad increase). Bone fusion could be obtained at the end of lengthening or within short weeks (Healing Index down to 8D/cm)Non-compliant patients (or using morphine), lost weight and MC.ConclusionsIncreasing by 8–10cm muscle length, even bilaterally, and maintaining MC during lengthening, is possible, with very fast bone fusion. It requires building up several hundred of grams of muscles.The ‘building up equation’ associating resistance bike from the early post-operative phase with sports, strong food intake with increased protein intake, and added supplements with no morphine medication, proved to boost circumferences and bone fusion. It induced fast recovery, walking and sports capacities.

Long-term glucocorticoid infusion impairs epididymal adipocyte metabolism and maturation and affects miR-150–5p actions

The most common form of hypercortisolism is iatrogenic Cushing's syndrome. Lipodystrophy and metabolic disorders can result from the use of exogenous glucocorticoids (GC). Adipocytes play an important role in the production of circulating exosomal microRNAs, and knockdown of Dicer promotes lipodystrophy. The aim of this study is to investigate the effect of GCs on epididymal fat and to assess their influence on circulating microRNAs associated with fat turnover. The data indicate that despite the reduction in adipocyte volume due to increased lipolysis and apoptosis, there is no difference in tissue mass, suggesting that epididymal fat pad, related to animal size, is not affected by GC treatment. Although high concentrations of GC have no direct effect on epididymal microRNA-150–5p expression, GC can induce epididymal adipocyte uptake of microRNA-150–5p, which regulates transcription factor Ppar gamma during adipocyte maturation. In addition, GC treatment increased lipolysis and decreased glucose-derived lipid and glycerol incorporation. In conclusion, the similar control and GC epididymal fat mass results from increased dense fibrogenic tissue and decreased adipocyte volume induced by the lipolytic effect of GC. These findings demonstrate the complexity of epididymal fat. They also highlight how this disease alters fat distribution. This study is the first in a series published by our laboratory showing the detailed mechanism of adipocyte turnover in this disease.

White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy-based therapy.

White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.

Partial CArdiac Denervation to Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (pCAD-POAF): Study Protocol for a Randomized Controlled Trial

Postoperative atrial fibrillation (POAF) is commonly seen in patients undergoing coronary artery bypass grafting (CABG), increasing the risk of morbidity, mortality and hospital expenses. This study is aimed to evaluate the effect of partial cardiac denervation, which is achieved by cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove, on the prevention of POAF after CABG. Patients planned for CABG at our center will be screened for eligibility for this study. A total of 430 patients will be randomized into intervention (partial cardiac denervation) group and control group. Intraoperative high-frequency electrical stimulation and further histologic analysis will be performed among certain number of patients to confirm the existence of ganglia. All of the patients will be continuously monitored for the incidence of POAF through electrophysiologic device until the 6th day postoperatively, and required to complete a 30-day follow-up (twelve lead electrocardiogram and echocardiogram assesment) after discharge. The primary endpoint is the incidence of POAF, while the secondary endpoints are the cost-effectiveness and safety outcomes. In conclusion, this trial will evaluate whether partial cardiac denervation through cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove can reduce the incidence of POAF after CABG. If this procedure is revealed to be effective and safe, it may provide a potential therapeutic approach to prevent POAF in this group of patients.

Transcutaneous lower eyelid blepharoplasty with micro-autologous fat transplantation harvested from orbital fat pads for lower eyelid aging treatment

The aging process of lower eyelids results in lower eyelid wrinkles, tear troughs, and eye bags. Many therapies have been described for treatment of lower eyelid aging, and transcutaneous blepharoplasty is often used for treating cases with eyebags and dermatochalasis. However, it may cause depression near the medial orbit resulting in a hollowed look. In the present study, we developed an innovative method transferring the herniated fatty tissue to volume loss area during the surgical procedure of transcutaneous lower eyelid blepharoplasty by means of micro-autologous fat transplantation harvested from resected orbital fat pads. Besides, we also analyze it efficacy and safety compared with traditional methods of transcutaneous lower eyelid blepharoplasty. We reviewed the records of the patients who underwent transcutaneous lower eyelid blepharoplasty with and without micro-autologous fat transplantation, for lower eyelid aging improvement. We used global aesthetic improvement scale, Hirmand's classification system, and Wrinkle Severity Rating Scale to evaluate the cosmetic outcome at 1week, 1month, and 3months after operation by two independent investigators. We found patients received transcutaneous lower eyelid blepharoplasty with autologous fat graft had significantly higher global aesthetic improvement scale and Wrinkle Severity Rating Scale improvement than those underwent transcutaneous lower eyelid blepharoplasty only in each evaluation timepoints. There was no significant difference of adverse effects between both surgical methods. The present study demonstrated the efficacy and safety of the lower eyelid blepharoplasty with micro-autologous fat transplantation harvesting from resected orbital fat pads.

Carryover effects of maternal late-gestation heat stress on granddaughters' growth and mammary gland development

Maternal (F0) exposure to late-gestation heat stress reduces their daughter's (F1) mammary gland fat pad mass (FP), parenchyma (PAR) mass, and epithelial cell proliferation when evaluated at birth and weaning, and go on to produce less milk in their first lactation. Herein, we investigated the effect of maternal late-gestation heat stress on whole-body growth and mammary development of their granddaughters (F2). Multiparous F0 cows had access to heat abatement (n = 41, shade, and active cooling via fans and water soakers) or not (n = 41, shade only) for the last 56 d of gestation during a subtropical summer. Consequently, the F1 daughters, born to F0 cows, were heat-stressed (HTF1, n = 36) or cooled (CLF1, n = 37) in utero during the last 2 mo of gestation. All F1 heifers were raised as an identically managed cohort until first calving. The F2 granddaughters, born to HTF1 (HTF2, n = 12) or CLF1 (CLF2, n = 17), were raised as an identically managed cohort until 70 d of age. Dry matter intake (DMI), body weight, hip height, wither height, chest girth, head circumference, mammary gland teat length, and left-right and front-rear teat distances were measured. Average daily gain (ADG) was calculated for the pre-weaned period (0-49 d). Mammary ultrasounds were performed on d 21, 49, and 70 (n = 9/group) on the rear left and right quarters to quantify PAR and FP areas. Mammary biopsies were collected for histological evaluation of epithelial structures (H&E staining), and to quantify cells positive for ERα (estrogen receptor, α subunit), cell proliferation (Ki67), and apoptosis (TUNEL). Heifer growth from birth to d 49 was similar between CLF2 and HTF2 for all parameters evaluated. Distances between teats and teat length were not different between groups. On d 70, CLF2 tended to have a greater average PAR (right and left quarters) relative to HTF2. Although the left FP was smaller in HTF2 relative to CLF2, the average FP was not different. The lumenal and non-lumenal epithelial structures in the PAR of HTF2 were significantly smaller than those of CLF2. In addition, HTF2 had a reduced percentage of proliferating cells in the epithelial and stromal compartments and a greater percentage of apoptotic cells, particularly in the stroma. The percentage of ERα positive cells was significantly reduced in HTF2. In summary, although HTF2 heifer's DMI was similar and they grew at the same rate as CLF2 heifers throughout the pre-weaning phase, their mammary glands had smaller PAR areas with fewer epithelial structures characterized by reduced cell turnover and lower ERα expression. These early changes in the microstructure and cellular turnover of the mammary gland may partly explain the reduction in lactation performance relative to CLF2 counterparts at maturity.