A new combined protocol to treat the dentin hypersensitivity associated with non-carious cervical lesions: A randomized controlled trial

The goal of this research is to assess the desensitizing effect of a diode laser on noncarious cervical lesions (NCCLs) responsible for dentin hypersensitivity (DH) in two separate output forces implemented both independently and in sequential combination modalities. A randomized controlled trial for this study was applied. Sixty-nine NCCLs responsible for DH pain with severity between 6 and 9 on the VAS scale were considered. Three study groups were developed using just one lesion from three different quadrants of the oral cavity of each patient. All treatment procedures were conducted using a laser diode (810 nm, 5 W) with varying power outputs used separately or in combination. The pain by DH was evaluated at baseline, at treatment completion, and at 15 days and 3 months after each laser procedure. Data analysis was performed using a Wilcoxon test for paired samples, a one-way ANOVA test, and an unpaired t-test. The significant reduction of the mean VAS score was estimated in each study group immediately and at 15 days and 3 months after the end of treatment and compared with the baseline mean VAS score (p-value < 0.0001). The best result concerning the improvement of DH symptomatology was assessed when a combined protocol of two different output powers of the diode laser was used. The authors conclude that the diode laser (810 nm) therapy procedure combining two separate output forces (low and high power) can improve the painful symptoms of DH from NCCLs

Regenerative potential of DPSCs and revascularization. direct, paracrine or autocrine effect?

A new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration. Graphical abstract: [Figure not available: see fulltext.

Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies

Cardiovascular outcome trials (CVOT) showed that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with significant cardiovascular benefits. However, CVOT are scarcely representative of everyday clinical practice, and real-world studies could provide clini-cians with more relatable evidence. Here, literature was thoroughly searched to retrieve real-world studies investigating the cardiovascular and renal outcomes of GLP-1RA vs. other glucose-lowering drugs and carry out relevant meta-analyses thereof. Most real-world studies were conducted in populations at low cardiovascular and renal risk. Of note, real-world studies investigating cardio-renal outcomes of GLP-1RA suggested that initiation of GLP-1RA was associated with a greater benefit on composite cardiovascular outcomes, MACE (major adverse cardiovascular events), all-cause mortality, myocardial infarction, stroke, cardiovascular death, peripheral artery disease, and heart failure compared to other glucose-lowering drugs with the exception of sodium-glucose transporter-2 inhibitors (SGLT-2i). Initiation of SGLT-2i and GLP-1RA yielded similar effects on composite cardiovascular outcomes, MACE, stroke, and myocardial infarction. Conversely, GLP-1RA were less effective on heart failure prevention compared to SGLT-2i. Finally, the few real-world studies addressing renal outcomes suggested a significant benefit of GLP-1RA on estimated glomerular filtration rate (eGFR) reduction and hard renal outcomes vs. active comparators except SGLT-2i. Further real-world evidence is needed to clarify the role of GLP-1RA in cardio-renal protection among available glucose-lowering drugs

25-hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25-hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin-sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin-sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin-sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low-density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin-sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = -0.58; P = 0.01), PTH (r = -0.44; P 0.01), insulin-sensitivity (r = -0.43; P < 0.01), total (r = -0.34; P = 0.030) and LDL (r = -0.40; P = 0.023) (but not high-density lipoprotein (HDL)) cholesterol, and triglycerides (r = -0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin-sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = -0.52; P < 0.01), whereas insulin-sensitivity was not significant. Our study suggested that there is no cause-effect relationship between vitamin D and insulin-sensitivity. In obesity, both low 25(OH)D concentration and insulin-resistance appear to be dependent on the increased body size. © 2010 The Obesity Society

Targeting lipid rafts as a strategy against coronavirus

Lipid rafts are functional membrane microdomains containing sphingolipids, including gangliosides, and cholesterol. These regions are characterized by highly ordered and tightly packed lipid molecules. Several studies revealed that lipid rafts are involved in life cycle of different viruses, including coronaviruses. Among these recently emerged the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The main receptor for SARS-CoV-2 is represented by the angiotensin-converting enzyme-2 (ACE-2), although it also binds to sialic acids linked to host cell surface gangliosides. A new type of ganglioside-binding domain within the N-terminal portion of the SARS-CoV-2 spike protein was identified. Lipid rafts provide a suitable platform able to concentrate ACE-2 receptor on host cell membranes where they may interact with the spike protein on viral envelope. This review is focused on selective targeting lipid rafts components as a strategy against coronavirus. Indeed, cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, consequently impairing coronavirus adhesion and binding. Moreover, these compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Furthermore, cyclodextrins can assemble into complexes with various drugs to form host–guest inclusions and may be used as pharmaceutical excipients of antiviral compounds, such as lopinavir and remdesivir, by improving bioavailability and solubility. In conclusion, the role of lipid rafts-affecting drugs in the process of coronavirus entry into the host cells prompts to introduce a new potential task in the pharmacological approach against coronavirus

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

The role of cardiolipin as a scaffold mitochondrial phospholipid in autophagosome formation: In vitro evidence

Cardiolipin (CL) is a hallmark phospholipid localized within the inner mitochondrial membrane. Upon several mitochondrial stress conditions, CL is translocated to specialized plat-forms, where it may play a role in signaling events to promote mitophagy and apoptosis. Recent studies characterized the molecular composition of MAM-associated lipid microdomains and their implications in regulating the autophagic process. In this study we analyzed the presence of CL within MAMs following autophagic stimulus and the possible implication of raft-like microdomains enriched in CL as a signaling platform in autophagosome formation. Human 2FTGH fibroblasts and SKNB-E-2 cells were stimulated under nutrient deprivation with HBSS. MAM fraction was obtained by an ultracentrifugation procedure and analyzed by HPTLC immunostaining. CL interactions with mitofusin2 (MFN2), calnexin (CANX) and AMBRA1 were analyzed by scanning confocal microscopy and coimmunoprecipitation. The analysis revealed that CL accumulates in MAMs fractions following autophagic stimulus, where it interacts with MFN2 and CANX. It associates with AMBRA1, which in turn interacts with BECN1 and WIPI1. This study demonstrates that CL is present in MAM fractions following autophagy triggering and interacts with the multimolecular complex (AMBRA1/BECN1/WIPI1) involved in autophagosome formation. It may have both structural and functional implications in the pathophysiology of neurodegenerative disease(s)

Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives

Several studies have shown that vitamin D may play a role in many biochemical mechanisms in addition to bone and calcium metabolism. Recently, vitamin D has sparked widespread interest because of its involvement in the homeostasis of the cardiovascular system. Hypovitaminosis D has been associated with obesity, related to trapping in adipose tissue due to its lipophilic structure. In addition, vitamin D deficiency is associated with increased risk of cardiovascular disease (CVD) and this may be due to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which it might modulate cardiovascular risk are not fully understood. Given this background, in this work we summarise clinical retrospective and prospective observational studies linking vitamin D levels with cardio-metabolic risk factors and vascular outcome. Moreover, we review various randomised controlled trials (RCTs) investigating the effects of vitamin D supplementation on surrogate markers of cardiovascular risk. Considering the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D replacement therapy in this population may be warranted; however, further RCTs are urgently needed to establish when to begin vitamin D therapy, as well as to determine the dose and route and duration of administration. © 2011 Elsevier B.V

Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy