Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis.

CONTEXT: Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results. OBJECTIVE: To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations. DATA SOURCE AND STUDY SELECTION: MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality. DATA EXTRACTION: Performed independently by two investigators, using a standardized data extraction sheet. DATA SYNTHESIS: In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45). CONCLUSIONS: Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease

Efficacy, feasibility and tolerability of ketogenic diet for the treatment of poor response to bariatric surgery

AbstractPurpose: Poor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition. Methods: A real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated.Results: A significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected.Conclusion: Our data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery.Abstract Purpose: Poor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition. Methods: A real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated. Results: A significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected. Conclusion: Our data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery

The Middle Pleistocene human metatarsal from Sedia del Diavolo (Rome, Italy)

The peopling of Europe during the Middle Pleistocene is a debated topic among paleoanthropologists. Some authors suggest the coexistence of multiple human lineages in this period, while others propose a single evolving lineage from Homo heidelbergensis to Homo neanderthalensis. The recent reassessment of the stratigraphy at the Sedia del Diavolo (SdD) site (Latium, Italy), now dated to the beginning of marine isotope stage (MIS) 8, calls for a revision of the human fossils from the site. In this paper, we present the morphometric, biomechanical and palaeopathological study of the second right metatarsal SdD2, to both re-evaluate its taxonomical affinities and possibly determine the levels of physical activity experienced by the individual during lifetime. Results demonstrate the persistence of archaic features in SdD2 suggesting new insights into the technology and hunting strategies adopted by Homo between MIS 9 and MIS 8

Haplotype Structure of the ENPP1 Gene and Nominal Association of the K121Q Missense Single Nucleotide Polymorphism With Glycemic Traits in the Framingham Heart Study

OBJECTIVE—A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K→Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium with it

ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies

The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities

The DEMO magnet system – Status and future challenges

We present the pre-concept design of the European DEMO Magnet System, which has successfully passed the DEMO plant-level gate review in 2020. The main design input parameters originate from the so-called DEMO 2018 baseline, which was produced using the PROCESS systems code. It defines a major and minor radius of 9.1 m and 2.9 m, respectively, an on-axis magnetic field of 5.3 T resulting in a peak field on the toroidal field (TF) conductor of 12.0 T. Four variants, all based on low-temperature superconductors (LTS), have been designed for the 16 TF coils. Two of these concepts were selected to be further pursued during the Concept Design Phase (CDP): the first having many similarities to the ITER TF coil concept and the second being the most innovative one, based on react-and-wind (RW) Nb3Sn technology and winding the coils in layers. Two variants for the five Central Solenoid (CS) modules have been investigated: an LTS-only concept resembling to the ITER CS and a hybrid configuration, in which the innermost layers are made of high-temperature superconductors (HTS), which allows either to increase the magnetic flux or to reduce the outer radius of the CS coil. Issues related to fatigue lifetime which emerged in mechanical analyses will be addressed further in the CDP. Both variants proposed for the six poloidal field coils present a lower level of risk for future development. All magnet and conductor design studies included thermal-hydraulic and mechanical analyses, and were accompanied by experimental tests on both LTS and HTS prototype samples (i.e. DC and AC measurements, stability tests, quench evolution etc.). In addition, magnet structures and auxiliary systems, e.g. cryogenics and feeders, were designed at pre-concept level. Important lessons learnt during this first phase of the project were fed into the planning of the CDP. Key aspects to be addressed concern the demonstration and validation of critical technologies (e.g. industrial manufacturing of RW Nb3Sn and HTS long conductors, insulation of penetrations and joints), as well as the detailed design of the overall Magnet System and mechanical structures

Advance in the conceptual design of the European DEMO magnet system

The European DEMO, i.e. the demonstration fusion power plant designed in the framework of the Roadmap to Fusion Electricity by the EUROfusion Consortium, is approaching the end of the pre-conceptual design phase, to be accomplished with a Gate Review in 2020, in which all DEMO subsystems will be reviewed by panels of independent experts. The latest 2018 DEMO baseline has major and minor radius of 9.1 m and 2.9 m, plasma current 17.9 MA, toroidal field on the plasma axis 5.2 T, and the peak field in the toroidal-field (TF) conductor 12.0 T. The 900 ton heavy TF coil is prepared in four lowerature-superconductor (LTS) variants, some of them differing slightly, other significantly, from the ITER TF coil design. Two variants of the CS coils are investigated - a purely LTS one resembling the ITER CS, and a hybrid coil, in which the innermost layers made of HTS allow the designers either to increase the magnetic flux, and thus the duration of the fusion pulse, or to reduce the outer radius of the CS coil. An issue presently investigated by mechanical analyzes is the fatigue load. Two variants of the poloidal field coils are being investigated. The magnet and conductor design studies are accompanied by the experimental tests on both LTS and HTS prototype samples, covering a broad range of DC and AC tests. Testing of quench behavior of the 15 kA HTS cables, with size and layout relevant for the fusion magnets and cooled by forced flow helium, is in preparation.</p

A sub-analysis of the SAGE study in Italy indicates good glycemic control in type 1 diabetes

Background and aims: Intensive glycemic control minimizes the risk of micro- and macrovascular complications in patients with type 1 diabetes (T1D). We report glycemic control in Italian participants (age groups: 26–44, 45–64, and ≥65 years) of the global SAGE study. Methods and results: The primary endpoint was proportion of participants who achieved an HbA1c &lt;7% in predefined age groups. In the 523 patients with T1D, mean age was 44.6 years and mean body mass index (BMI) was 25 kg/m2. Mean HbA1c was 7.5% and 29.4% had HbA1c &lt;7.0%, with the highest percentage in those 26–45 years (31.7%) and the lowest in those ≥65 years (20%). Altogether, 22.9% of patients achieved their physician-established individualized HbA1c target. Most patients had ≥1 symptomatic hypoglycemic episode in the previous 3 months (≤70 mg/dL 82.5%; ≤54 mg/dL 61%). Severe hypo- and hyperglycemia were experienced by 16.3% and 12% of patients, of which 7.1 and 9.5%, respectively, required hospitalization/emergency visits. More patients achieved HbA1c &lt;7% with CSII (30%) than with multiple daily insulin injections (27.9%). In multivariate analysis, BMI (OR 0.94, 95% CI 0.89–0.99, p = 0.032) and adherence to diet (OR 0.36, 95% CI 0.18–0.70, p = 0.0028) were significantly associated with HbA1c &lt;7.0%. Conclusions: Glycemic control can be considered good in the Italian SAGE cohort, especially in younger patients, who more frequently use pumps/continuous glucose monitoring. Greater patient education and use of technology may further support this achievement. Patients should be encouraged to maintain a low BMI and adhere to their diet