Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients.

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo.

Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here.

Modified fish-incision technique in brachioplasty: a surgical approach to correct excess skin and fat of the upper arm (restoring the armpit contour).

UNLABELLED: Brachial ptosis is one of the consequences of massive weight loss. At an early stage, brachial ptosis can be corrected by liposuction, dermolipectomy and liposuction, or minibrachioplasty while the most advanced stage requires extended brachioplasty. Since brachioplasty was first described, various techniques have been proposed in the management of upper extremity contour deformities. Modifications to the original technique were mainly made to shape arm contour, to obtain good morphological reconstruction with attention directed toward improving and refining the resulting scar. We describe a modified approach to the "fish incision" technique defining a preoperative marking procedure that permits the reduction of overcorrection problems to reshape and improve the contour of the armpit with camouflage of scar sequelae. Our modifications to the original technique focus on incision placement along the medial bicipital groove and armpit, based on the the drawings of the tails following dynamic lines of the armpit contour established by the underlying muscles. We drew the tails slightly with a 60° angle between the tails and the width depending on patient's arm contour and on the excess of the skin in the armpit to be removed. The modified technique has obtained satisfactory results for patients and may be considered as a new surgical approach in the management of brachial ptosis. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A useful method to overcome the difficulties of applying silicone gel sheet on irregular surfaces.

To date, silicone gel and silicone occlusive plates are the most useful and effective treatment options for hypertrophic scars (surgical and traumatic). Use of silicone sheeting has also been demonstrated to be effective in the treatment of minor keloids in association with corticosteroid intralesional infiltration. In our practice, we encountered four problems: maceration, rashes, pruritus and infection. Not all patients are able to tolerate the cushion, especially children, and certain anatomical regions as the face and the upper chest are not easy to dress for obvious social, psychological and aesthetic reasons. In other anatomical regions, it is also difficult to obtain adequate compression and occlusion of the scar. To overcome such problems of applying silicone gel sheeting, we tested the use of liquid silicone gel (LSG) in the treatment of 18 linear hypertrophic scars (HS group) and 12 minor keloids (KS group) as an alternative to silicone gel sheeting or cushion. Objective parameters (volume, thickness and colour) and subjective symptoms such as pain and pruritus were examined. Evaluations were made when the therapy started and after 30, 90 and 180 days of follow-up. After 90 days of treatment with silicone gel alone (two applications daily), HS group showed a significant improvement in terms of volume decrease, reduced inflammation and redness and improved elasticity. In conclusion, on the basis of our clinical data, we find LSG to be a useful method to overcome the difficulties of applying silicone gel sheeting on irregular surface.

Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues.

Stem cell based therapies for the repair and regeneration of various tissues are of great interest for a high number of diseases. Adult stem cells, instead, are more available, abundant and harvested with minimally invasive procedures. In particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to differentiate into bone, cartilage, and adipose tissues. Human adult adipose tissue seems to be the most abundant source of MSCs and, due to its easy accessibility; it is able to give a considerable amount of stem cells. In this study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This stem cell population displayed higher proliferative capacity than CD34(-) CD90(-) cells and was able to differentiate in vitro into adipocytes (PPARγ(+) and adiponectin(+)) and endothelial cells (CD31(+) VEGF(+) Flk1(+)). In addition, in methylcellulose without VEGF, it formed a vascular network. The aim of this study was to investigate differentiation potential of human adipose CD34(+) /CD90(+) stem cells loaded onto commercial collagen sponges already used in clinical practice (Gingistat) both in vitro and in vivo. The results of this study clearly demonstrate that human adult adipose and loose connective tissues can be obtained in vivo, highlighting that CD34(+) /CD90 ASCs are extremely useful for regenerative medicine.

Clinical and histologic effects from CO2 laser treatment of keloids.

Keloids and hypertrophic scars are abnormal responses to wound healing. In general, keloids exhibit a proliferative growth beyond the margins of the scar and remain persistent; while hypertrophic scars are contained to the original wound and may regress over time. In particular, keloid formation is one of the most challenging clinical problems, with increasing frequency in surgical practice. Many treatments are available such as intralesional corticosteroids, topical applications, cryotherapy, surgical excision, radiation therapy, silicone gel sheeting, pressure therapy, and laser therapy. There are no set guidelines for the treatment of keloids and the most common treatments are individualized and depended on the distribution, size, thickness, and consistency of lesions. The authors have evaluated carbon dioxide laser successfully in the treatment of keloids and the aim of this study was to determine the immediate and long-term histologic and clinical effects of keloids after carbon dioxide laser. Fifty consecutive patients (40 females, 10 males, ages 18-60 years, mean age 40 years) with moderate to severe keloids were evaluated. All the patients received regional treatments (deltoid, elbow, chin, and ear) in an outpatient setting with a high-energy pulsed CO2 laser. Significant immediate and prolonged clinical improvement in skin tone, texture, and appearance of carbon dioxide laser was examined in all patients. Dermal remodeling was observed also on histologic examination of biopsied tissue after treatment. Carbon dioxide laser appears to be effective and well tolerated for the treatment of keloids, avoiding the adverse effects and lengthy recovery time.

Management of prepubertal gynecomastia in two monozygotic twins with Peutz-Jeghers syndrome: from aromatase inhibitors to subcutaneous mastectomy.

BACKGROUND: Prepubertal gynecomastia is characterized by the presence of palpable uni- or bilateral breast tissue in boys without other signs of sexual maturation. It may be the endocrine expression of rare syndromes such as Peutz-Jeghers syndrome (PJS). This study aimed to evaluate the effectiveness of anastrozole and to describe an innovative surgical approach. METHODS: This report presents twins with PJS, bilateral prepubertal gynecomastia, and testicular multifocal calcifications. Both twins were treated with anastrozole for 2 years. After finishing treatment, both were followed before subcutaneous mastectomy was performed by the "modified" Webster technique. RESULTS: Growth velocity decreased and gynecomastia diminished during anastrozole treatment. After discontinuation of therapy due to a sharp reduction in growth velocity, both twins showed regrowth of gynecomastia, with painful and strained breasts. A significant reduction in breast volume with glandular removal was achieved. CONCLUSIONS: The findings of this study showed a multidisciplinary approach to prepubertal gynecomastia due to the synergy of pediatricians, radiologists, and plastic surgeons. The follow-up evaluation after the anastrozole treatment showed it to be an efficacious medical treatment, as an alternative to orchidectomy, to control the effects of circulating estrogens. Moreover, the results observed in the patients confirmed the validity and feasibility of the "modified" Webster technique in terms of aesthetic and functional results, patient satisfaction, and absence of complications.

Hyaluronic acid-based fillers in patients with autoimmune inflammatory diseases.

The use of hyaluronic acid (HA)-based aesthetic therapies is growing steadily, and according to the International Society of Aesthetic Plastic Surgery, more than 4.3 million aesthetic procedures using HA were performed in 2019, an increase of 15.7% than 2018. More people are offering these types of services, often without proper training or qualifications. Therefore, there is an increasing number of reports in the literature relating to possible adverse events, with subsequent therapeutic problems and more or less serious consequences for patients. The aim of this research is to carry out a review of the literature in order to evaluate the impact of hyaluronic acid-based fillers in patients with autoimmune inflammatory diseases, in particular scleroderma and Systemic Lupus Erythematosus (SLE). Although HA plays a central role in the inflammatory process, the use of HA-based fillers in patients with autoimmune inflammatory diseases is still controversial. HA, in fact, in inflamed tissues helps to propagate the inflammatory response and, injected in the form of a dermal filler, could potentially promote reactivation of the underlying disease. For this reason, many specialists do not perform HA-based aesthetic treatments in patients with scleroderma or SLE. However, recent scientific evidence suggests that the use of HA-based fillers in patients with scleroderma can lead to improvement of skin lesions, with satisfactory results. In the literature, there are no clinical studies that contraindicate the administration of HA-based dermal fillers in patients with inflammatory disease.

Effects of a new centrifugation method on adipose cell viability for autologous fat grafting.

The use of adipose tissue transfer in plastic and reconstructive surgery is not new and has been studied extensively. Due to different results with regard to adipose cell damage and the level of survival of the transferred tissue in clinical practice, the authors aimed to investigate the effects of centrifugation on fat aspirates to optimize the centrifugal force for fat transplantation and to obtain an increased number of intact adipose progenitor cells. The following different centrifugation forces were evaluated in vitro in terms of fat decantation: 3,000 rpm (1,500×g), 1,300 rpm (250×g), and 500 rpm (50×g). Moreover, the density level, morphology of fat cells, cell viability, and progenitor cell number also were evaluated. Centrifugation leads to a good fat tissue density, with a significant number of progenitor cells, and efficiently removes the liquid portion. High centrifugal forces (at 3,000 rpm) caused significant damage to fat cells with low cell viability, whereas very low centrifugal forces (at 500 rpm) showed little effect on adipose tissue density, resembling fat decantation. Fat aspirates, withdrawn from 30 healthy donors in vivo, were centrifuged at different rotations per minute (rpm), as follows. For the 10 patients in group A, Coleman's technique was used with a centrifugation of the aspirated fat at 3,000 rpm (1,500×g) for 3 min. For the 10 patients in group B, the authors' technique was used, with centrifugation of the aspirated fat at 1,300 rpm (250×g) for 5 min. For the 10 patients in group C, simple decantation of fat was used. In conclusion, a centrifugal force of 1,300 rpm resulted in better density of adipose tissue, with good cell viability and increased ability to preserve a significant number of progenitor cells.

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study.

OBJECTIVES: This study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women. BACKGROUND: To our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women. METHODS: Prospective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition. RESULTS: The propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation. CONCLUSIONS: Among pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217).

Effects of intensive lifestyle changes on erectile dysfunction in men.

INTRODUCTION: Limited data are available supporting the notion that treatment of lifestyle risk factors may improve erectile dysfunction (ED). AIM: In the present study, we analyzed the effect of a program of changing in lifestyle designed to improve erectile function in subjects with ED or at increasing risk for ED. METHODS: Men were identified in our database of subjects participating in randomized controlled trials evaluating the effect of lifestyle changes. A total of 209 subjects were randomly assigned to one of the two treatment groups. The 104 men randomly assigned to the intervention program received detailed advice about how to reduce body weight, improve quality of diet, and increase physical activity. The 105 subjects in the control group were given general information about healthy food choices and general guidance on increasing their level of physical activity. MAIN OUTCOME MEASURES: Changes in erectile function score (International Index of Erectile Function-5 [IIEF-5]; items 5, 15, 4, 2, and 7 from the full-scale IIEF-15) and dependence of the restoration of erectile function on the changes in lifestyle that were achieved. RESULTS: Erectile function score improved in the intervention group. At baseline, 35 subjects in the intervention group and 38 subjects in the control group had normal erectile function (34% and 36%, respectively). After 2 years, these figures were 58 subjects in the intervention group and 40 subjects in the control group, respectively (56% and 38%, P = 0.015). There was a strong correlation between the success score and restoration of erectile function. CONCLUSIONS: It is possible to achieve an improvement of erectile function in men at risk by means of nonpharmacological intervention aiming at weight loss and increasing physical activity.

Role of subcutaneous abdominal fat on cardiac function and proinflammatory cytokines in premenopausal obese women.

The role of surgically removing subcutaneous fat by abdominoplasty on circulating inflammatory markers and myocardial dysfunction, evaluated by myocardial performance index (MPI), were investigated. Twenty volunteers submitted to the abdominoplasty (abdominoplasty group), and other 28 women treated by hypocaloric diet (diet group) were evaluated. Echocardiographic parameters of MPI, circulating levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, were performed at baseline and 2 months later. Compared with nonobese women, obese women had increased concentrations of TNF-alpha (P < 0.01), IL-6 (P < 0.01), and higher MPI (P < 0.02), indicating ventricular dysfunction. Subcutaneous fat concentrations of TNF-alpha and IL-6 were related to MPI impairment. After 60 days, waist-to hip ratio was significantly reduced in the abdominoplasty group. Anthropometric changes were accompanied by a significant decline in plasma concentrations of TNF-alpha and IL-6 levels as well as by significant improvements of MPI in abdominoplasty group compared with diet group. Abdominoplasty may represent a safe method for ameliorating cardiac function in obese women.

Cardiac syncope recurrence in type 2 diabetes mellitus patients vs. normoglycemics patients: The CARVAS study.

STUDY HYPOTHESIS: Cardiac autonomic dysfunction might lead to higher vaso vagal syncope (VVS) recurrence rate in type 2 diabetes mellitus (T2DM) patients vs. non diabetics patients. BACKGROUND: VVS recurrence might be due to alterations of autonomic system function, as assessed by heart rate variability (HRV). To date, in this study we investigated the correlation between HRV alterations and VVS recurrence at 12 months of follow up in T2DM vs. non T2DM patients. MATERIALS AND METHODS: In a prospective multicenter study we studied a propensity score matching (PSM) analysis of 121 T2DM vs. 121 non T2DM patients affected by VVS. RESULTS: T2DM vs. non T2DM patients had at baseline a higher rate of HRV dysfunction, and this was linked to higher rate of VVS recurrence at 12 months of follow up (p < 0.05). Blood pressure alterations and lower LF/HF ratio were linked to higher rate of all cause syncope recurrence, and of vasodepressor, cardio inhibitory, and mixed syncope recurrence (p < 0.05). Anti hypertensive drug therapies increased the number of vasodepressor and mixed syncope events (p < 0.05); alterations of heart rate increased syncope recurrence and mixed syncope recurrence events (p < 0.05). Finally, T2DM was linked to higher rate of VVS recurrence, and specifically of vasodepressor and mixed VVS recurrence (p < 0.05). CONCLUSIONS: T2DM patients have alterations of the autonomic nervous system, as result of cardiac autonomic neuropathy. However, T2DM diagnosis and autonomic dysfunction assessed by HRV alterations predicted VVS recurrence.

HLA-G and anti-HCV in patients on the waiting list for kidney transplantation.

PURPOSE: Human leukocyte antigen (HLA)-G is a non-classic major histocompatibility complex HLA class I molecule. HLA-G may have tolerogenic properties which are linked to epigenetic-sensitive pathways. There is a correlation of sHLA-G levels and graft acceptance in transplantation studies. There are previous data on correlation of sHLA-G with graft rejection as well as with viral infections such as hepatitis C virus (HCV) in kidney transplanted patients. Here, we report the sHLA-G expression in patients on the waiting list for kidney transplantation, with and without anti-HCV compared to a control group. METHODS: Serum of 67 patients on the waiting list for kidney transplantation (n = 43 with anti-HCV and n = 24 without anti-HCV) was analyzed. Among these patients, n = 39 were on the waiting list for the first transplantation, while n = 28 were patients who returned in the list. The control group included n = 23 blood donors with anti-HCV (n = 13) and without anti-HCV (n = 10). RESULTS: The expression of sHLA-G was significantly lower in the control group (39.6 ±â€¯34.1 U/ml) compared to both - patients on the waiting list for the first transplantation (62.5 ±â€¯42.4 U/ml, p=0.031) and patients who returned in the list (76.7 ±â€¯53.9 U/ml, p=0.006). No significant differences were observed in all anti-HCV positive groups. A positive linear correlation between sHLA-G and TNF-α, and patient age was observed. CONCLUSIONS: Serum sHLA-G values were significantly increased in both - patients on the waiting list for the first transplantation and patients who returned in the list, as compared to control group. Our findings confirm the key tolerogenic role of sHLA-G levels as epigenetic-related marker for measuring the state of kidney allograft acceptance.

Effects of incretin treatment on cardiovascular outcomes in diabetic STEMI-patients with culprit obstructive and multivessel non obstructive-coronary-stenosis.

BACKGROUND: No proper data on prognosis and management of type-2 diabetic ST elevation myocardial infarction (STEMI) patients with culprit obstructive lesion and multivessel non obstructive coronary stenosis (Mv-NOCS) exist. We evaluated the 12-months prognosis of Mv-NOCS-diabetics with first STEMI vs.to non-diabetics, and then Mv-NOCS-diabetics previously treated with incretin based therapy vs. a matched cohort of STEMI-Mv-NOCS never treated with such therapy. METHODS: 1088 Patients with first STEMI and Mv-NOCS were scheduled for the study. Patients included in the study were categorized in type 2 diabetics (n 292) and non-diabetics (n 796). Finally, we categorized diabetics in current-incretin-users (n 76), and never-incretin-users (n 180). The primary end point was all cause deaths, cardiac deaths, and major adverse cardiac events (MACE) at 12 months of follow up. RESULTS: The study results evidenced higher percentage of all cause deaths (2.2% vs. 1.1%, p value 0.05), cardiac deaths (1.6% vs. 0.5%, p value 0.045), and MACE (12.9% vs. n 5.9%), p value 0.001) in diabetic vs. no diabetic patients at 12 months follow up. Among diabetic patients, the current vs never-incretin-users, did not present a significant difference about all cause of deaths, and cardiac deaths through 12-months. The MACE rate at 1 year was 7.4% in diabetic incretin-users STEMI Mv-NOCS patients vs. 12.9% in diabetic never-incretin-users STEMI-Mv-NOCS patients (p value 0.04). In a risk-adjusted hazard analysis, MACE through 12 months were lower in diabetic STEMI-Mv NOCS incretin-users vs never-incretin-users patients (HR 0.513, CI [0.292-0.899], p 0.021). Consequently, lower levels of glucagon-like peptide 1(GLP-1) were predictive of MACE at follow up (HR 1.528, CI [1.059-2.204], p 0.024). CONCLUSION: In type 2 diabetic patients with STEMI-Mv-NOCS, we observed higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared to non-diabetic STEMI-Mv-NOCS patients. In diabetic patients, never-incretin-users have worse prognosis as compared to current-incretin-users.Trail registration Clinical trial number: NCT03312179, name of registry: clinicaltrialgov, URL: clinicalltrialgov.com, date of registration: September 2017, date of enrollment first participant: September 2009.

Inflammatory Cytokines and SIRT1 Levels in Subcutaneous Abdominal Fat: Relationship With Cardiac Performance in Overweight Pre-diabetics Patients.

Objectives: In obese patients the superficial adipose tissue expresses cytokines, and sirtuins, that may affect myocardial function. In this study, we investigated the effect of metformin therapy added to a hypocaloric diet on the inflammatory pattern and cardiac performance (MPI) in obese patients with pre-diabetic condition. Materials and Methods: Fifty-eight obese patients that were enrolled for abdominoplastic surgery were divided into patients with pre-diabetic condition (n 40) and normo-glycemic patients (n18). Patients with pre-diabetic condition were randomly assigned to metformin therapy added to a hypocaloric diet (group 1, n 20) or to a hypocaloric diet therapy alone (group 2, n20). Patients with normo-glycemic condition were assigned to a hypocaloric diet therapy. Results: During enrollment, obese patients with a pre-diabetic condition (group 1 and 2) presented higher glucose values, lower values of insulin, and higher values of the homeostasis model for the assessment of insulin resistance (HOMA-IR) than obese patients with normo-glycemic condition(group 3). In addition, they had higher values of C Reactive protein (CRP), interleukin 6 (IL6), and lower values of sirtuin 1(SIRT1). In the 12th month of the follow-up, metformin therapy induced in patients with pre-diabetic condition (group 1) a significant reduction of glucose values, HOMA-IR, and inflammatory markers such as CRP (1.04 ± 0.48 vs. 0.49 ± 0.02 mmol/L, p < 0.05), IL6 (4.22 ± 0.45 vs. 3.33 ± 0.34 pg/ml, p < 0.05), TNFα (6.95 ± 0.59 vs. 5.15 ± 0.44 pg/ml, p < 0.05), and Nitrotyrosine (5,214 ± 0,702 vs. 2,151 ± 0,351 nmol/l, p < 0.05). This was associated with a significant reduction of Intima-media thickness (1.01 ± 0.15 vs. 0.86 ± 0.15 mm, p < 0.05), Septum (14 ± 2.5 vs. 10.5 ± 2 mm, p < 0.05), Posterior wall (11 ± 1.5 vs. 8 ± 1 mm, p < 0.05), LV mass (192.5 ± 49.5 vs. 133.2 ± 37.6 g, p < 0.05) and of MPI (0.58 ± 0.03 vs. 0.38 ± 0.02, p < 0.05). At 12 months of follow-up, group 2 experienced only a reduction of cholesterol (4.15 ± 0.94 vs. 4.51 ± 0.88 mmol/L, p < 0.05) and triglycerides (1.71 ± 1.18 vs. 1.83 ± 0.54 mmol/L, p < 0.05). At 12 months of follow-up, group 3 experienced a significant reduction of inflammatory markers, and also of echographic parameters, associated with amelioration of myocardial performance. To date, IL6 expression was related to higher values of left ventricle mass (R-value 0.272, p-value 0.039), and to higher IMT (R-value 0.272, p-value 0.039), such as those observed for CRP (R-value 0.308, p-value 0.021), for glucose blood values (R-value 0.449, p-value 0.001), and for HOMA-IR (R-value 0.366, p-value 0.005). An inverse correlation was found between subcutaneous fat expression of SIRT1 and myocardial performance index (R-value-0.236, p-value 0.002). Conclusion: In obese patients with pre-diabetic condition a metformin therapy may reduce inflammation and oxidative stress, and this may be associated with the amelioration of the cardiac performance. Clinical research trial number: NCT03439592.

Human melanoma metastases express functional CXCR4.

PURPOSE: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. EXPERIMENTAL DESIGN: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. RESULTS: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 mumol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. CONCLUSIONS: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.

Epigenetics and type 1 diabetes: mechanisms and translational applications.

Type 1 diabetes (T1D) is an irreversible degenerative disease with severe complications such as heart disease, nephropathy, neuropathy, and retinopathy. Although exogenous insulin administration is a life-saving therapy, it does not cure the disease. This review addresses the epigenetic mechanisms responsible for the development of T1D and discusses epigenetic-based strategies for prevention and treatment of the disease. We describe novel epigenetic biomarkers for the identification of susceptible individuals and the establishment of innovative therapies with epidrugs and cell therapy to regenerate the lost ß-cells. Despite the wealth of promising data regarding the potential benefits of epigenetic tools to reduce the burden of T1D, clinical trials are still very few, and this issue needs to be resolved in the near future.

Augmentation Mastopexy with Implant and Autologous Tissue for Correction of Moderate/Severe Ptosis.

PURPOSE: Breast augmentation combined with mastopexy is associated with a significantly higher complication rate than augmentation alone. The combination of mastopexy and breast implants has revealed a moderate recurrence of breast ptosis in many patients particularly with use of medium to large implants. Ptosis is the "bottoming out" of the breast tissue with loss of the desired roundness, due to the ptosis of the breast implant and the mammary tissue. In this study, we hypothesize the need for careful planning and careful preoperative surgical execution to minimize this complication. PATIENTS AND METHODS: Between January 2007 and July 2011, augmentation mastopexy with implant and autologous tissue ("double implant") was performed for 25 patients with grade III mammary ptosis. All patients underwent inverted-T mastopexy with supramuscular moderately cohesive gel breast implant using an inferior-based flap of de-epitelialized dermoglandular tissue and a superior-based nipple-areola complex pedicle. RESULTS: An inferior-based flap of deepithelialized dermoglandular tissue was used to stabilize the implant and is projection. Breast lifting was performed through a strong anchorage to fascia and to muscle of second intercostal space, improving the profile of the breast. Results were analyzed, no breast ptosis recurrence was noted at 30-month follow-up. CONCLUSIONS: Our technique presents the challenge of determining the amount of excess skin to be removed after implantation to create symmetry and provide for skin tightening without compromising tissue vascularization.

Differential effects of all-trans-retinoic acid (RA) on Erk1/2 phosphorylation and cAMP accumulation in normal and malignant human prostate epithelial cells: Erk1/2 inhibition restores RA-induced decrease of cell growth in malignant prostate cells.

OBJECTIVE: All-trans-retinoic acid (RA) regulates cellular growth, differentiation and apoptosis in human prostate by binding to RA receptors. Non-genomic retinoid effects on signal transduction kinases in the cytoplasm are also described in several cells but they are still unknown in prostate cells. METHODS: Using an epithelial cell line derived from normal human prostate (EPN), and normal (NPEC) and malignant (CPEC) epithelial primary cultures of human prostate, we have examined effects of RA on both extracellular signal-regulated kinase 1/2 (Erk1/2) and cAMP accumulation. Then we have verified the effect of the inhibition of Erk1/2 on RA-induced growth arrest and apoptosis in malignant cells. RESULTS: In NPEC and in EPN treated with RA for up to 24 h, Western blot analyses of Erk1/2 phosphorylation show that RA causes a rapid activation of Erk1/2 within 5 min, which is maintained for 30 min, followed by a return to basal levels. In CPEC, the activated phosphorylation levels persist up to 24 h. While basal cAMP levels are not affected by 30 min treatment with RA in both EPN and NPEC, levels are increased in CPEC. Forskolin-induced cAMP levels are decreased by RA in all cell types. CPEC were incubated for up to 96 h with RA with and without the inhibitor of Erk1/2, UO126. CPEC incubated with RA and UO126 for 72 h showed a significant arrest of cell growth and after 96 h apoptosis in 11% of cells. CONCLUSIONS: We show rapid effects of RA on cytoplasmic messenger pathways in human prostate, and that responses can differ between normal and malignant cells. The inhibition of these pathways could improve the efficiency of RA in prostate cancer growth control.