Geodetic Kinematic Terrestrial Navigation using a MMS – Multi-constellation and multi-frequency Galileo/GPS/GLONASS performance comparisons

This paper presents a part of the research activities performed from 2019 to 2022 in the framework of WP 5.3 “Field campaign” and in particular, the activities “Land urban and extra-urban data measurement campaigns” of the European GRC-MS (Galileo Reference Center – Member States) Project - GSA/GRANT/04/2016. The dynamic data-collection campaigns were conducted by three participating member states (Portugal, Italy, and Romania), in three different environments: aerial, terrestrial, and maritime, respectively. This article presents a comparison of the results obtained for the terrestrial environment, considering the performance of Galileo used in conjunction with other GNSS systems, such as GPS, using different geodetic and navigational multi-constellation and multifrequency receivers/devices experimental dynamic activities. Starting from the user’s needs and requirements, the experimental setup and the methodology for the estimation of the reference («actual») trajectory are provided. These are complemented by numerical results and reasons for possible performance degradations analyses. The processed rover trajectories and the produced outputs were compared to the reference trajectory obtained from GNSS/INS (INertial System) integrated high-performance solution. Galileo-only and GPS-only solutions, so as multi-system solutions (GPS+Galileo, GPS+GLONASS and GPS+GLONASS+Galileo) were analysed. PVT (Position Velocity Time) solutions were computed using post-processing geodetic interferential techniques. From the performed analyses, some preliminary conclusions relative to the Galileo performances applied to terrestrial urban and extraurban navigation were derived. These activities need to be continued in the near future, taking into consideration the Galileo constellation improvements and the ITS (Intelligent Transport Systems) applications in order to improve the offered services and the road safety

Sotagliflozin, the first dual SGLT inhibitor. Current outlook and perspectives

Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose. Well-designed clinical trials, have shown that sotagliflozin (as monotherapy or add-on therapy to other anti-hyperglycemic agents) improves glycated hemoglobin in adults with T2D, with beneficial effects on bodyweight and blood pressure. Similar results have been obtained in adults with T1D treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections, even after insulin optimization. A still ongoing phase 3 study is currently evaluating the effect of sotagliflozin on cardiovascular outcomes (ClinicalTrials.gov NCT03315143). In this review we illustrate the advantages and disadvantages of dual SGLT 2/1 inhibition, in order to better characterize and investigate its mechanisms of action and potentialities

Effect of Vitamin D Supplementation on Obesity-Induced Insulin Resistance: A Double-Blind, Randomized, Placebo-Controlled Trial

Objective: The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes. Methods: Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention. Results: Body weight in both groups decreased significantly (−7.5% in the vitamin D group and −10% in the placebo group; P < 0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg−1·min−1; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg−1·min−1; P = 0.84). Conclusions: Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity

Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes

BACKGROUND. The appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin, and a reduction of β cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifesting β cell dysfunction. The aim of this study was to verify the acute effect of one of these factors, the reduction of β cell mass, on the subsequent development of hyperglycemia. METHODS. To pursue this aim, nondiabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamp (HC) procedures, followed by arginine stimulation before and after surgery. Based on postsurgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal glucose tolerance (post-NGT), impaired glucose tolerance (post-IGT), or having diabetes mellitus (post-DM). RESULTS. At baseline, the 3 groups showed similar fasting glucose and insulin levels; however, examining the various parameters, we found that reduced first-phase insulin secretion, reduced glucose sensitivity, and rate sensitivity were predictors of eventual postsurgery development of IGT and diabetes. CONCLUSION. Despite comparable functional mass and fasting glucose and insulin levels at baseline and the very same 50% mass reduction, only reduced first-phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM)

Covid-19 and covid-like patients: A brief analysis and findings of two deceased cases

BACKGROUND: The predominant pattern of lung lesions in patients affected by coronavirus disease (COVID-19) disease is diffuse alveolar damage with massive thromboembolism similar as described in patients infected with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia were frequent. Importantly, the formation of platelet– fibrin thrombi in small vessels was seen consistent with coagulopathy, which appeared to be a common feature in patients who died of COVID-19. However, many were the cases found with similar COVID-19 symptomatology though negative results from nasal-pharyngeal swab performed by reverse transcription-polymerase chain reaction (RT-PCR). This latter typology of patients, otherwise named COVID-like, showed analogous clinical signs with similar arterial blood gas, cell blood count and laboratory parameters, and same computed tomography (CT)-scan ground-glass opacities. Symptoms such as cough, fever, and difficulty breathing were highly similar as well. Both forms, COVID-19 and COVID-like, are primarily respiratory with multi-organ involvement and both revealed comparable incubation periods often with a rapid onset and unexpected decay. CASE REPORT: In this brief paper, we described two cases regarding two deceased males, one confirmed COVID-19 (RT-PCR but not CT scan) and the second a COVID-like (negative for RT-PCR but positive to CT scan with ground-glass opacity) whom condition, disease patterns, and analysis were highly similar. CONCLUSION: Improved investigation is mandatory, in which RT-PCR and CT scan procedures are completed by data from more detailed laboratory analysis, ABG analysis, BALF, and a deeper clinical assessment

Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia

In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules

Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes

Aims/hypothesis: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. Methods: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. Results: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. Conclusions/interpretation: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity. Graphical abstract: [Figure not available: see fulltext.

GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

BACKGROUND: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. METHODS: Randomised trial of usual care versus GP-initiated PCC for women aged 18–40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI) before PCC (STAI-1) and after (STAI-2). After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3). RESULTS: The mean STAI-1-score (n = 466) was 36.4 (95% CI 35.4 – 37.3). Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4 – 4.8). Mean scores of the STAI-3 were 38.5 (95% CI 37.7 – 39.3) in the control group (n = 1090) and 38.7 (95% CI 37.9 – 39.5) in the intervention group (n = 1186). CONCLUSION: PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety. Trial Registration: ISRCTN5394291