Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

Introduction: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S), like other hypoabsorptive procedures, could be burdened by long-term nutritional deficiencies such as malnutrition, anemia, hypocalcemia, and hyperparathyroidism. Objectives: We aimed to report our experience in terms of mid-term (2 years) bariatric, nutritional, and metabolic results in patients who underwent SADI-S both as a primary or revisional procedure. Methods: One hundred twenty-one patients were scheduled for SADI-S as a primary or revisional procedure from July 2016 to February 2020 and completed at least 2 years of follow-up. Demographic features, bariatric, nutritional, and metabolic results were analyzed during a stepped follow-up at 3 months, 6 months, 1 year and 2 years. Results: Sixty-six patients (47 female and 19 male) were included. The median preoperative BMI was 53 (48–58) kg/m². Comorbidities were reported in 48 (72.7%) patients. At 2 years, patients had a median BMI of 27 (27–31) kg/m² (p < 0.001) with a median %EWL of 85.3% (72.1–96.1), a TWL of 75 (49–100) kg, and a %TWL of 50.9% (40.7–56.9). The complete remission rate was 87.5% for type 2 diabetes mellitus, 83.3% for obstructive sleep apnea syndrome and 64.5% for hypertension. The main nutritional deficiencies post SADI-S were vitamin D (31.82%) and folic acid deficiencies (9.09%). Conclusion: SADI-S could be considered as an efficient and safe procedure with regard to nutritional status, at least in mid-term (2 years) results. It represents a promising bariatric procedure because of the excellent metabolic and bariatric outcomes with acceptable nutritional deficiency rates. Nevertheless, larger studies with longer follow-ups are necessary to draw definitive conclusions.

Neurological disorders like Parkinson disease and Alzheimer disease, spinal cord injury and stroke have some recurrent characteristics such as abnormal protein aggregation, oxidative stress induction, apoptosis, excitotoxicity, perturbation of intracellular Ca2+ homeostasis and inflammation. To date, there are few effective treatments available and the drugs currently used to manage the symptoms have important side effects. Therefore, research studies are focusing on natural phytochemicals present in diet as bioactive molecules potentially useful against neurodegenerative diseases. In this review, we will discuss the neuroprotective role of palmitoylethanolamide, hydroxytyrosol, and Bacopa monnieri extracts against neuroinflammation and neurodegeneration, thereby revealing their remarkable potential as novel therapeutic options for the treatment of neurodegenerative disorders. (www.actabiomedica.it)

Neuropilins are transmembrane coreceptors expressed by endothelial cells and neurons. NRP1 and NRP2 bind a variety of ligands, by which they trigger cell signaling, and are important in the development of lymphatic valves and lymphatic capillaries, respectively. This study focuses on identifying rare variants in the NRP1 and NRP2 genes that could be linked to the development of lymphatic malformations in patients diagnosed with lymphedema. Two hundred and thirty-five Italian lymphedema patients, who tested negative for variants in known lymphedema genes, were screened for variants in NRP1 and NRP2. Two probands carried variants in NRP1 and four in NRP2. The variants of both genes segregated with lymphedema in familial cases. Although further functional and biochemical studies are needed to clarify their involvement with lymphedema and to associate NRP1 and NRP2 with lymphedema, we suggest that it is worthwhile also screening lymphedema patients for these two new candidate genes.

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet–Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery.

Background. ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the ARAP3 gene are associated with impaired lymphatic vessel formation. Objective. The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the ARAP3 gene in order to explore its role in the development of lymphedema. Methods and Results. We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including ARAP3. Three out of 235 probands proved to carry rare missense heterozygous variants in ARAP3. In the case of two families, other family members were also tested and proved negative for the ARAP3 variant, besides being unaffected by lymphedema. According to in silico analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins. Conclusions. Based on our results, we propose that variants in ARAP3 could be included in genetic testing for lymphedema.