Gut Microbiota Profile Changes in Patients with Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease: A Metagenomic Study.

Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were stratified into four groups: IBD-NAFLD, IBD-only, NAFLD-only patients, and healthy controls (CTRLs). The 16S rRNA was sequenced by Next-Generation Sequencing. Bioinformatics and statistical analysis were performed. Bacterial α-diversity showed a significant lower value when the IBD-only group was compared to the other groups and particularly against the IBD-NAFLD group. ß-diversity also showed a significant difference among groups. The higher Bacteroidetes/Firmicutes ratio was found only when comparing IBD groups and CTRLs. Comparing the IBD-only group with the IBD-NAFLD group, a decrease in differential abundance of Subdoligranulum, Parabacteroides, and Fusicatenibacter was found. Comparing the NAFLD-only with the IBD-NAFLD groups, there was a higher abundance of Alistipes, Odoribacter, Sutterella, and Lachnospira. An inverse relationship in the comparison between the IBD-only group and the other groups was shown. For the first time, the singularity of the gut microbial composition in IBD and NAFLD patients has been shown, implying a potential microbial signature mainly influenced by gut inflammation.

Exploring the impact of lipid droplets on the evolution and progress of hepatocarcinoma.

Over the past 10 years, the biological role of lipid droplets (LDs) has gained significant attention in the context of both physiological and pathological conditions. Considerable progress has been made in elucidating key aspects of these organelles, yet much remains to be accomplished to fully comprehend the myriad functions they serve in the progression of hepatic tumors. Our current perception is that LDs are complex and active structures managed by a distinct set of cellular processes. This understanding represents a significant paradigm shift from earlier perspectives. In this review, we aim to recapitulate the function of LDs within the liver, highlighting their pivotal role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) (Hsu and Loomba, 2024) and their contribution to the progression towards more advanced pathological stages up to hepatocellular carcinoma (HC) (Farese and Walther, 2009). We are aware of the molecular complexity and changes occurring in the neoplastic evolution of the liver. Our attempt, however, is to summarize the most important and recent roles of LDs across both healthy and all pathological liver states, up to hepatocarcinoma. For more detailed insights, we direct readers to some of the many excellent reviews already available in the literature (Gluchowski et al., 2017; Hu et al., 2020; Seebacher et al., 2020; Paul et al., 2022).

How may we effectively motivate people to reduce the consumption of meat? Results of a meta-analysis of randomized clinical trials.

PURPOSE: Excessive meat consumption (MC) is associated with multiple health risks. Additionally, it can undermine environmental sustainability and affect the potential improvement of animal welfare. The aim of this study was to assess the efficacy of literacy interventions (LIs) in reducing MC. METHODS: Studies assessing the efficacy of LIs addressing health risks, environmental sustainability and/or animal welfare in reducing MC were searched. We used random-effects meta-analysis to estimate the overall efficacy and conducted subgroup analyses to identify the most effective information contents. Additionally, meta-regression analyses investigated participants' age, LI duration, and follow-up length influence on LIs' efficacy. RESULTS: Fourteen studies involving more than ten thousand subjects were meta-analyzed. The pooled estimate showed that LIs had a small (Hedges's g = 0.15; 95%CI: 0.06-0.25) but statistically significant effect in reducing MC. Subgroup analysis showed that the highest efficacy was achieved when subjects were alarmed about health risks (g = 0.29; 95% CI: -0.02, 0.60), compared to informing about the risks for the environment (g = 0.18; 95% CI: -0.15, 0.51) and for animal welfare (g = 0.02; 95%CI: -0.08, 0.11). The meta-regression analysis indicated that LIs had greater efficacy in younger individuals and when the intervention duration was longer. Conversely, it was suggested that efficacy improves as the length of follow-up increases. CONCLUSIONS: Informing about health risks related to MC temporarily decreased its intake, while informing about the impact on environmental sustainability or animal welfare was ineffective. Furthermore, long-lasting LIs achieve long-term dietary change toward MC.

Association of dietary patterns with sarcopenia in adults aged 50 years and older.

PURPOSE: Although numerous studies have investigated the impact of dietary factors on the prevention of decreased muscle mass and function, limited research has examined the relationship between dietary patterns and sarcopenia. This study aimed to assess the associations between dietary patterns, and sarcopenia, muscle strength, and mass in adults following a Mediterranean diet residing in southern Italian cities. METHODS: This cross-sectional study utilized data from an existing database, comprising 528 individuals aged 50 years or older who underwent health-screening tests at the Clinical Nutrition Unit of the "R.Dulbecco" University Hospital. Strength was assessed through handgrip strength, and appendicular skeletal muscle mass was estimated using bioelectrical impedance analysis. Dietary intake information was collected through a food frequency questionnaire linked to the MetaDieta 3.0.1 nutrient composition database. Principal Component Analysis, a statistical technique identifying underlying relationships among different nutrients, was employed to determine dietary patterns. Multinomial logistic regression analysis was conducted to estimate the odds ratio for sarcopenia or low handgrip strength in relation to the lowest tertile of dietary pattern adherence compared to the highest adherence. RESULTS: The participants had a mean age of 61 ± 8 years. Four dietary patterns were identified, with only the Western and Mediterranean patterns showing correlations with handgrip strength and appendicular skeletal muscle mass. However, only the Mediterranean pattern exhibited a correlation with sarcopenia (r = - 0.17, p = 0.02). The highest tertile of adherence to the Mediterranean dietary pattern demonstrated significantly higher handgrip strength compared to the lowest tertile (III Tertile: 28.3 ± 0.5 kg vs I Tertile: 26.3 ± 0.5 kg; p = 0.01). Furthermore, even after adjustment, the highest tertile of adherence to the Mediterranean pattern showed a significantly lower prevalence of sarcopenia than the lowest adherence tertile (4% vs 16%, p = 0.04). The lowest adherence to the Mediterranean dietary pattern was associated with increased odds of having low muscle strength (OR = 2.38; p = 0.03; 95%CI = 1.05-5.37) and sarcopenia (OR = 9.69; p = 0.0295; %CI = 1.41-66.29). CONCLUSION: A high adherence to the Mediterranean dietary pattern, characterized by increased consumption of legumes, cereals, fruits, vegetables, and limited amounts of meat, fish, and eggs, is positively associated with handgrip strength and appendicular skeletal muscle mass. The highest adherence to this dietary model is associated with the lowest odds of low muscle strength and sarcopenia. Despite the changes brought about by urbanization in southern Italy compared to the past, our findings continue to affirm the superior benefits of the Mediterranean diet in postponing the onset of frailty among older adults when compared to other dietary patterns that are rich in animal foods.

The Effects of Online Home-Based Pilates Combined with Diet on Body Composition in Women Affected by Obesity: A Preliminary Study.

Diet and exercise intervention are the first strategies to counteract obesity. An online home-based exercise program may be a feasible approach in an obese population. Therefore, this study aimed to investigate the effects of twelve weeks of online Pilates plus diet on body composition in individuals affected by obesity. Thirty-five females were randomly assigned to a home-based Pilates group (PG, n = 18) or a group without intervention (control group, CG, n = 17). All participants followed a Mediterranean diet. The PG followed a twelve-week online Pilates Matwork program (three times/week; 180 min/week), while the CG was not involved in any structured physical exercise program. Body composition and handgrip strength were evaluated at baseline (T0) and after the intervention (T1). A significant group × time interaction (p < 0.05) was found for the fat mass percentage (pFM). Specifically, the pFM was significantly lower at T1 than at T0 in the PG. Significant group × time interactions for fat-free mass (p < 0.05), appendicular skeletal muscle mass (p < 0.05), and skeletal muscle mass (p < 0.01) were found. All these variables were significantly higher at T1 than at T0 in the PG (p < 0.05). Home-based Pilates combined with diet intervention may represent an effective strategy to improve body composition in terms of fat mass reduction and muscle mass gain in adults affected by obesity.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis : Platelets in cardiovascular risk.

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography.

AIM: To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). METHODS: We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. RESULTS: Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (ß = 0.274, P = 0.008) and fasting insulin levels (ß = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (ß = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. CONCLUSION: Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.

A nutraceutical with Citrus bergamia and Cynara cardunculus improves endothelial function in adults with non-alcoholic fatty liver disease.

OBJECTIVE: Polyphenol intake may prevent hepatic steatosis and cardiovascular disease by potentially improving endothelial function. The purposes of this study are to investigate the association between fatty liver disease and endothelial dysfunction and to test the effects of a nutraceutical containing extracts made from Citrus bergamia and Cynara cardunculus on peripheral vascular endothelial function in adults with liver steatosis. METHODS: We analyzed data from 32 individuals with hepatic steatosis and endothelial dysfunction (reactive hyperemia index ≤ 1.67). Sixteen subjects took 1 capsule/d (300 mg/d) containing Cynara cardunculus extract and bergamot polyphenol fraction, while the other 16 subjects matched for age, sex, and body mass index took 1 capsule/d of placebo (maltodextrin) for 12 wk. All anthropometric parameters were assessed at baseline and after 12 wk as were lipids, glucose, and reactive hyperemia index using an EndoPAT 2000. RESULTS: The mean age was 52 ± 9 y. The mean reactive hyperemia index was 1.15 ± 0.4. After 12 wk, we found a greater increase in reactive hyperemia index in the participants taking the nutraceutical rather than placebo (0.58 ± 0.5 versus 0.13 ± 0.5; P = 0.02, respectively). The stepwise multivariable analysis confirmed a positive association between reactive hyperemia index change and the nutraceutical treatment (B = 0.38; P = 0.025) and negative association with reactive hyperemia index values at baseline (B = -0.81; P < 0.001). No association was found between the reduction in the amount of intrahepatic fat and the improvement of endothelial function (B = 0.002; P = 0.56). CONCLUSIONS: A nutraceutical containing bergamot and artichoke extracts improves peripheral vascular endothelial function in adults with hepatic steatosis and early phase of atherosclerosis.

Assessment of Mediterranean Citrus Peel Flavonoids and Their Antioxidant Capacity Using an Innovative UV-Vis Spectrophotometric Approach.

Citrus fruits exert various beneficial health effects due to the large amount of polyphenols they contain. Citrus peels, often considered food waste, contain several health-promoting polyphenols. Among these, flavonoids have long been quantified through colorimetric assays which, if not adequately applied, can lead to conflicting results. Flavonoids possess strong antioxidant properties and can decrease circulating free radicals, thereby reducing oxidative stress phenomena. Quantifying flavonoids and properly estimating their antioxidant capacity allows us to predict plausible beneficial effects of citrus fruits on human health. The aim of this research was to analyze the advantageous phenolic compounds found in the peels of citrus fruits commonly found in the Mediterranean region. The objective was to measure their antioxidant capacity and ability to neutralize free radicals. To achieve this purpose, UV-visible spectrophotometric analyses, liquid chromatography (LC) and Electron Paramagnetic Spectroscopy (EPR) were utilized and compared, finally suggesting an innovative approach for assessing the overall flavonoid content by the nitrite-aluminum assay. HPLC data demonstrated that hesperidin was the most abundant flavonoid in all peel extracts except for orange peels, in which naringin was the predominant flavonoid. The total flavonoid content was greater than 1.3 mg/mL in all extracts, with tangerine and orange yielding the best results. Citrus peel polyphenols exerted strong antioxidant and free radical scavenging effects, inhibiting up to 75% of the free radicals used as reference in the EPR analyses.

The impact of endometriosis on dietary choices and activities of everyday life: a cross-sectional study.

Introduction: Endometriosis is characterized by ectopic endometrial tissue and severe pain; frequently, women afflicted by this condition resort to non-medical interventions, such as dietary modifications. The aim of this study is to assess the impact of endometriosis on dietary patterns and quality of life. Methods: An online survey was conducted among Italian women with endometriosis to gather self-reported demographic, clinical, dietary habit, and daily life data post-diagnosis. Results: A total of 4,078 participants were included. Following an endometriosis diagnosis, 66% reported changes in eating habits, and 92% experienced a decline in daily life. Respondents chose dietary interventions: gluten-free (15%), anti-inflammatory (8%), Mediterranean (7.1%), or ketogenic (4%) diets, to improve health and reduce symptoms. The study revealed a shift in eating habits, with increased consumption of vegetables, fruits (10%), cereals, legumes (6.6%), and fish (4.5%), while reducing dairy products (18.4%), soy-containing foods (6.7%), and high saturated fats (8%). Eating habit changes correlated with endometriosis stages and worsened daily life. Educational level, endometriosis stages, years of symptoms, and eating habit changes linked to changes in daily life. Conclusion: Our findings emphasize the importance of monitoring eating behaviors to prevent unhealthy habits and malnutrition in women with endometriosis. Further studies are needed to evaluate how different diets impact symptoms and enhance daily life for these individuals.

Efficacy of intra-articular injections of hyaluronic acid in patients with glenohumeral joint osteoarthritis: A systematic review and meta-analysis.

Symptomatic primary glenohumeral (GH) joint osteoarthritis (OA) can be challenging to treat. Hyaluronic acid (HA) has emerged as a promising treatment for the nonsurgical management of GH-OA. In this systematic review with meta-analysis, we aimed to evaluate the current evidence regarding the efficacy of intra-articular HA on pain relief in patients suffering from GH-OA. A total of 15 studies (only randomized controlled trials providing data at the end of the intervention) were included. The relevant studies were selected based on the following PICO model: P: patients with diagnosis of shoulder OA; I: HA infiltrations as therapeutic intervention administered; C: no restriction for comparators assessed; O: pain, in terms of visual analog scale (VAS) or numeric rating scale. The risk of bias among the included studies was estimated using the PEDro scale. A total of 1023 subjects were analyzed. Comparing HA injections combined with physical therapy (PT) compared to PT alone resulted in superior scores, showing an overall effect size (ES) of 4.43 (p = 0.00006). Moreover, pooled analysis of VAS pain scores demonstrated a significant improvement in the ES of the HA in comparison with corticosteroid injections (p = 0.002). On average, we reported a PEDro score of 7.2. A total of 46.7% of studies showed probable signs of a randomization bias. The findings of this systematic review and meta-analysis showed that IA injections of HA might be effective on pain relief with significant improvements compared to baseline and compared to corticosteroid injections in patients affected by GH-OA.

Therapeutic Fasting in Reducing Chemotherapy Side Effects in Cancer Patients: A Systematic Review and Meta-Analysis.

The aim of this study was to assess the available evidence regarding the effect of a variety of fasting-like regimens on preventing chemotherapy-related side effects. PubMed, Scopus and Embase were used to select the studies for this review, which concluded on 24 November 2022. All types of clinical trials and case series reporting chemotherapy toxicity associated with fasting regimens and any comparison were considered. A total of 283 records were identified, of which 274 were excluded, leaving only nine studies that met the inclusion criteria. Five of these trials were randomized. Overall, moderate to high-quality evidence showed that several fasting regimens did not provide benefits compared to a conventional diet or other comparators in reducing the risk of adverse events. The overall pooled estimate for a variety of fasting regime when compared to non-fasting, indicated no significant difference in the side effects (RR = 1.10; 95% CI: 0.77-1.59; I2 = 10%, p = 0.60), including neutropenia alone (RR = 1.33; 95% CI: 0.90-1.97; I2 = 0%, p = 0.15). A sensitivity analysis confirmed these results. Based on our systematic review and meta-analysis, there is currently no evidence supporting the superiority of therapeutic fasting over non-fasting in preventing chemotherapy toxicity. The development of cancer treatment that do not entail toxicities remains imperative.

Preventing muscle wasting: pro-insulin C-peptide prevents loss in muscle mass in streptozotocin-diabetic rats.

BACKGROUND: C-peptide therapy exerts several positive actions on nerves, vasculature, smooth muscle relaxation, kidney function and bone. To date, the role of C-peptide in preventing type 1 diabetes-related muscle atrophy has not been investigated. Our aim was to evaluate if C-peptide infusion prevents muscle wasting in diabetic rats. METHODS: Twenty-three male Wistar rats were randomly divided into three groups: normal control group, diabetic group and diabetic group plus C-peptide. Diabetes was induced by streptozotocin injection, and C-peptide was administered subcutaneously for 6 weeks. The blood samples were obtained at baseline, before streptozotocin injection and at the end of the study to assess C-peptide, ubiquitin and other laboratory parameters. We also tested the ability of C-peptide to regulate the skeletal muscle mass, the ubiquitin-proteasome system, the autophagy pathway as well as to improve muscle quality. RESULTS: C-peptide administration reversed hyperglycaemia (P = 0.02) and hypertriglyceridaemia (P = 0.01) in diabetic plus C-peptide rats compared with diabetic control rats. The diabetic-control animals displayed a lower weight of the muscles in the lower limb considered individually than the control rats and the diabetic plus C-peptide rats (P = 0.03; P = 0.03; P = 0.04; P = 0.004, respectively). The diabetic-control rats presented a significantly higher serum concentration of ubiquitin compared with the diabetic plus C-peptide and the control animals (P = 0.02 and P = 0.01). In muscles of the lower limb, the pAmpk expression was higher in the diabetic plus C-peptide than the diabetic-control rats (in the gastrocnemius, P = 0.002; in the tibialis anterior P = 0.005). The protein expression of Atrogin-1 in gastrocnemius and tibialis was lower in the diabetic plus C-peptide than in diabetic-control rats (P = 0.02, P = 0.03). After 42 days, the cross-sectional area in the gastrocnemius of the diabetic plus C-peptide group had been reduced by 6.6% while the diabetic-control rats had a 39.5% reduction compared with the control animals (P = 0.02). The cross-sectional area of the tibialis and the extensor digitorum longus muscles was reduced, in the diabetic plus C-peptide rats, by 10% and 11%, respectively, while the diabetic-control group had a reduction of 65% and 45% compared with the control animals (both P < 0.0001). Similar results were obtained for the minimum Feret's diameter and perimeter. CONCLUSIONS: C-peptide administration in rats could protect skeletal muscle mass from atrophy induced by type 1 diabetes mellitus. Our findings could suggest that targeting the ubiquitin-proteasome system, Ampk and muscle-specific E3 ubiquitin ligases such as Atrogin-1 and Traf6 may be an effective strategy for molecular and clinical intervention in the muscle wasting pathological process in T1DM.

Effects of a Functional Ice Cream Enriched with Milk Proteins on Bone Metabolism: A Feasibility Clinical Study and In Vitro Investigation.

Background: Milk proteins (MPs) and their derivative whey proteins (WPs) are important components of human diet that might prevent bone loss. We aimed to investigate the effects of MP on the bones of postmenopausal women, along with the effects of WP on osteoblast cells. Methods: We conducted a feasibility controlled clinical study with 62 postmenopausal women who were asked to consume an MP-enriched ice cream. We also investigated the effect of WP on the ERK1/2 and AKT pathways, RUNX2, alkaline phosphatase, RANKL/OPG ratio, and COL1A of Saos-2. Results: After 12 weeks, we found a greater bone mineral density and bone alkaline phosphatase reduction in women who consumed the MP-enriched ice cream compared to the control group (p = 0.03 and p = 0.02, respectively). In Saos-2 cells, WP upregulated ERK1/2 and AKT pathways (p = 0.002 and p = 0.016), cell proliferation (p = 0.03), and osteoblast differentiation markers, along with downregulating RANKL/OPG (p < 0.001). Moreover, the inhibition of ERK1/2 by PD184253 reverted the effects on both the RUNX2 and ALP mRNA expression and cells proliferation (p = 0.028, p = 0.004, and p = 0.003, respectively) when treated with WP. Conclusions: WP upregulates cell proliferation, RUNX2, and alkaline phosphatase through the activation of the ERK1/2 pathways on Saos-2. These mechanisms probably contribute to preventing bone loss in postmenopausal women.

Preparing Patients for Cosmetic Surgery and Aesthetic Procedures: Ensuring an Optimal Nutritional Status for Successful Results.

Aesthetic and cosmetic medical practices have attracted considerable consumer attention globally. However, possible complications vary and range from mild, self-resolving ecchymoses or edema to more persistent complications. The aim of this review is to identify the nutritional deficits or excesses associated with the major complications of reconstructive surgery, aesthetic surgery, and mini-invasive aesthetic procedures. An additional goal is to provide a bundle of actions for professionals working in the industry in order to reduce the risks of aesthetic procedures and improve the clinical outcomes. Granulomas, hypertrophic scars and keloids, seromas, infections and xerosis, hyperpigmentation, petechiae, livedo reticularis, slower wound healing, and other poor outcomes are frequently associated with nutritional deficiencies. Nutritional status can markedly affect wound healing and tissue repair following surgical interventions, as well as the outcomes of aesthetic and cosmetic medical practices. Professionals working in this industry, therefore, need to consider the nutritional aspects of their patients to obtain the best results.

Impact of microvascular complications on the outcomes of diabetic foot in type 2 diabetic patients with documented peripheral artery disease.

PURPOSE: Microvascular disease (MVD) is associated with amputation linked to peripheral artery disease (PAD) in the general population. No study evaluated the impact of diabetic microvascular complications on the outcomes of vascular diabetic foot ulcers (DFU). The aim of the study was to investigate whether retinopathy, nephropathy, and polyneuropathy can predict the outcomes of DFU in type 2 diabetic patients with PAD. METHODS: Three hundred and thirty-one consecutive patients with vascular DFU were enrolled and followed up for 44.1 ± 23.9 months. RESULTS: The prevalence of retinopathy was significantly higher in subjects with ulcer persistence (45.2%; p < 0.01), minor amputation (48.9%; p < 0.001), and major amputation (57.9%; p < 0.001) than in healed patients (23.3%), and in non-survivors than in survivors (64.9 versus 20.5%; p < 0.001). The prevalence of nephropathy was significantly greater in subjects with ulcer persistence (83.9%; p < 0.01), minor amputation (86.7%; p < 0.001), and major amputation (94.7%; p < 0.001) than in those with healed DFU (64.4%), and in non-survivors than in survivors (88.3 versus 65.7%; p < 0.001). The prevalence of polyneuropathy was significantly higher in non-survivors than in survivors (76.6 versus 61.0%; p = 0.012). Multivariate analysis showed that absence of retinopathy (OR: 0.451; 95% CI: 0.250-0.815; p < 0.001) and nephropathy (OR: 0.450; 95% CI: 0.212-0.951; p = 0.036) were independently associated with healing. Moreover, retinopathy was a predictor both of minor amputation (OR: 2.291; 95% CI: 1.061-4.949; p = 0.034) and mortality (OR: 5.274; 95% CI: 2.524-11.020; p < 0.001). Polyneuropathy never entered the regression model. CONCLUSIONS: Diabetic microvascular complications, in particular retinopathy, may predict the outcomes of vascular DFU. Longitudinal studies should confirm this finding.

Association of erectile dysfunction with diabetic foot and its outcomes in type 2 diabetic men.

PURPOSE: Erectile dysfunction (ED) and diabetic foot (DF) are common complications in patients with diabetes. However, the relationship between ED and DF has been little studied. In particular, no study has evaluated whether ED is associated with the outcomes of DF. The aim of this retrospective cohort study was to investigate whether ED is a predictor of the outcomes of DF in a large population of men with DF. METHODS: Three hundred and twenty-six consecutive men with type 2 diabetes and a recent and single DF ulcer were recruited and followed up for 41.7 ± 22.7 months. RESULTS: Among men with DF, 56.1% had ED (ED group) and 43.9% did not (NO ED group). Wound healing rate was significantly higher in the NO ED than in the ED group (90.2 versus 73.3%; p = 0.0001). Minor amputation rate (13.7 versus 4.8%; p = 0.007) and mortality (25.7 versus 0.7%; p < 0.001) were significantly greater in the ED than in the NO ED group. Among 263 patients with healed ulcers, recurrence rate was significantly higher in the ED than in the NO ED group (51.5 versus 26.3%; p < 0.001). Multivariate analysis showed that the absence of ED was associated with wound healing (OR: 0.459; 95% CI: 0.213-0.993; p = 0.048), while the presence of ED predicted mortality (OR: 22.644; 95% CI: 2.976-34.271; p = 0.002) and DF recurrence (OR: 3.498; 95% CI: 1.882-6.499; p < 0.001). CONCLUSIONS: Our data show that among men with DF the prevalence of ED is very high. Moreover, ED may be a strong predictor of wound healing, mortality, and ulcer recurrence.

A Comprehensive Therapeutic Patient Education May Improve Wound Healing and Reduce Ulcer Recurrence and Mortality in Persons With Type 2 Diabetes.

OBJECTIVES: The impact of a comprehensive therapeutic patient education (TPE) on the prognosis of diabetic foot ulcer (DFU) has not yet been evaluated in the literature. The purpose of this study was to determine whether TPE is a predictor of outcome in type 2 diabetes patients with DFU. METHODS: We evaluated 583 consecutive individuals with a recent and single DFU. They were treated and followed for 42.8±23.3 months. Patients were divided into 2 groups. The TPE group included subjects who had been receiving regular sessions of a comprehensive TPE, including a specific foot care education (FCE), for at least 12 months before DFU occurred (n=129). The non-TPE group comprised the remaining subjects (n=454). All 583 patients received intensive FCE during the treatment period. RESULTS: We identified a significantly higher percentage of healed DFUs (96.0% vs 74.9%; p<0.0001) and a lower percentage of major amputations (0.8% vs 4.4%; p=0.0511), minor amputations (1.6% vs 12.3%; p=0.0003), DFU persistence (1.6% vs 8.4%; p=0.0069) and deaths (1.6% vs 21.4%; p<0.0001) in the TPE group than in the non-TPE group. Among 464 patients with healed ulcers, the proportion of subjects with re-ulceration was greater in the non-TPE group than in the TPE group (48.8% vs 6.5%; p<0.0001). Multivariate analysis showed that TPE can predict healing (odds ratio [OR], 4.202; 95% confidence interval [CI], 1.604 to 11.004; p=0.0035) and may significantly reduce DFU recurrence (OR, 0.093; 95% CI, 0.043 to 0.201; p<0.0001) and mortality (OR, 0.096; 95% CI, 0.022 to 0.410; p=0.0016). CONCLUSION: A comprehensive TPE may have a positive impact on wound healing, ulcer recurrence and mortality in people with DFU.

The Effect of an Innovative Combination of Bergamot Polyphenolic Fraction and Cynara cardunculus L. Extract on Weight Gain Reduction and Fat Browning in Obese Mice.

Obesity is one of the world's most serious public health issues, with a high risk of developing a wide range of diseases. As a result, focusing on adipose tissue dysfunction may help to prevent the metabolic disturbances commonly associated with obesity. Nutraceutical supplementation may be a crucial strategy for improving WAT inflammation and obesity and accelerating the browning process. The aim of this study was to perform a preclinical "proof of concept" study on Bergacyn®, an innovative formulation originating from a combination of bergamot polyphenolic fraction (BPF) and Cynara cardunculus (CyC), for the treatment of adipose tissue dysfunction. In particular, Bergacyn® supplementation in WD/SW-fed mice at doses of 50 mg/kg given orally for 12 weeks, was able to reduce body weight and total fat mass in the WD/SW mice, in association with an improvement in plasma biochemical parameters, including glycemia, total cholesterol, and LDL levels. In addition, a significant reduction in serum ALT levels was highlighted. The decreased WAT levels corresponded to an increased weight of BAT tissue, which was associated with a downregulation of PPARγ as compared to the vehicle group. Bergacyn® was able to restore PPARγ levels and prevent NF-kB overexpression in the WAT of mice fed a WD/SW diet, suggesting an improved oxidative metabolism and inflammatory status. These results were associated with a significant potentiation of the total antioxidant status in WD/SW mice. Finally, our data show, for the first time, that Bergacyn® supplementation may be a valuable approach to counteract adipose tissue dysfunction and obesity-associated effects on cardiometabolic risk.

Correlative Raman-Electron-Light (CREL) Microscopy Analysis of Lipid Droplets in Melanoma Cancer Stem Cells.

Among all neoplasms, melanoma is characterized by a very high percentage of cancer stem cells (CSCs). Several markers have been proposed for their identification, and lipid droplets (LDs) are among them. Different techniques are used for their characterization such as mass spectrometry, imaging techniques, and vibrational spectroscopies. Some emerging experimental approaches for the study of LDs are represented by correlative light-electron microscopy and by correlative Raman imaging-scanning electron microscopy (SEM). Based on these scientific approaches, we developed a novel methodology (CREL) by combining Raman micro-spectroscopy, confocal fluorescence microscopy, and SEM coupled with an energy-dispersive X-ray spectroscopy module. This procedure correlated cellular morphology, chemical properties, and spatial distribution from the same region of interest, and in this work, we presented the application of CREL for the analysis of LDs within patient-derived melanoma CSCs (MCSCs).