Stress-energy tensor correlations across regular black holes horizons

Hawking radiation can be regarded as a spontaneous and continuous creation of virtual particle-antiparticle pairs outside the event horizon of a black hole where strong tidal forces prevent the annihilation: the particle escapes to infinity contributing to the Hawking flux, while its corresponding antiparticle partner enters the event horizon and ultimately reaches the singularity. The aim of this paper is to investigate the energy density correlations between the Hawking particles and their partners across the event horizon of two models of non-singular black holes by calculating the two-point correlation function of the density operator of a massless scalar field. This analysis is motivated by the fact that in acoustic black holes particle-partner correlations are signalled by the presence of a peak in the equal time density-density correlator. Performing the calculation in a Schwarzschild black hole it was shown in [1] that the peak does not appear, mainly because of the singularity. It is then interesting to consider what happens when the singularity is not present. In the Hayward and Simpson-Visser non-singular black holes we show that the density-density correlator remains finite when the partner particle approaches the hypersurface that replaces the singularity, opening the possibility that partner-particle correlations can propagate towards other regions of spacetime instead of being lost in a singularity.Comment: Version accepted for publication in PR

Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes

Background: Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality. Methods: A Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable. Our investigation was carried out in the Gargano Heart Study-prospective design, comprising 356 patients with type 2 diabetes, in whom both total and high molecular weight (HMW) adiponectin were measured and cardiovascular mortality was recorded (mean follow-up = 5.4 ± 2.5 years; 58 events/1922 person-year). Results: The A allele of rs822354 was associated with both total and HMW adiponectin [β (SE) = 0.10 (0.042), p = 0.014 and 0.17 (0.06), p = 0.003; respectively]. In a Poisson model comprising age, sex, smoking habits, BMI, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, insulin therapy and hypertension, both rs822354 (IRR = 1.94, 95 % CI 1.23-3.07; p = 0.005), as well as the genetic equivalent of total adiponectin change (IRR = 1.07, 95 % CI 1.02-1.12; p = 0.003) were significantly associated with cardiovascular mortality. The observed genetic effect was significantly greater than that exerted by the genetic equivalent change of serum adiponectin (p for IRR heterogeneity = 0.012). In the above-mentioned adjusted model, very similar results were obtained when HMW, rather than total, adiponectin was used as the exposure variable of interest. Conclusions: Our data suggest that the paradoxical association between high serum adiponectin levels and increased cardiovascular mortality rate is based on a cause-effect relationship, thus pointing to an unexpected deleterious role of adiponectin action/metabolism on atherosclerotic processes

Serum resistin is causally related to mortality risk in patients with type 2 diabetes: Preliminary evidences from genetic data

Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and allcause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n = 350), Gargano Mortality Study (n = 698) and Foggia Mortality Study (n = 431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p = 3.5 ∗ 10-7) with effect size modest for GRS = 1 and 2 and much higher for GRS >3, with respect to GRS = 0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p = 3.3 ∗ 10-2), with a low effect size for GRS = 1 and 2, and nearly doubled for GRS ≥ 3, with respect to GRS = 0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22-3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients

Chronic migraine long-term regular treatment with onabotulinumtoxinA: a retrospective real-life observational study up to 4 years of therapy

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The PPARγ2 P12A polymorphism is not associated with all-cause mortality in patients with type 2 diabetes mellitus

The high mortality risk of patients with type 2 diabetes mellitus may well be explained by the several comorbidities and/or complications. Also the intrinsic genetic component predisposing to diabetes might have a role in shaping the risk of diabetes-related mortality. Among type 2 diabetes mellitus SNPs, rs1801282 is of particular interest because (i) it is harbored by peroxisome proliferator-activated receptor-γ2 (PPARγ2), which is the target for thiazolidinediones which are used as antidiabetic drugs, decreasing all-cause mortality in type 2 diabetes mellitus, and (ii) it is associated with insulin resistance and related traits, risk factors for overall mortality in type 2 diabetes mellitus. We investigated the role of PPARγ2 P12A, according to a dominant model (PA + AA vs. PP individuals) on incident all-cause mortality in three cohorts of type 2 diabetes mellitus, comprising a total of 1672 patients (462 deaths) and then performed a meta-analysis of ours and all available published data. In the three cohorts pooled and analyzed together, no association between PPARγ2 P12A and all-cause mortality was observed (HR 1.02, 95 % CI 0.79–1.33). Similar results were observed after adjusting for age, sex, smoking habits, and BMI (HR 1.09, 95 % CI 0.83–1.43). In a meta-analysis of ours and all studies previously published (n = 3241 individuals; 666 events), no association was observed between PPARγ2 P12A and all-cause mortality (HR 1.07, 95 % CI 0.85–1.33). Results from our individual samples as well as from our meta-analysis suggest that the PPARγ2 P12A does not significantly affect all-cause mortality in patients with type 2 diabetes mellitus

Mobilization in early rehabilitation in intensive care unit patients with severe acquired brain injury: An observational study.

Objective: To determine whether early mobilization of patients with severe acquired brain injury, performed in the intensive/neurointensive care unit, influences functional outcome. Design: Prospective observational study. Setting: Fourteen centres in Italy. Subjects: A total of 103 consecutive patients with acquired brain injury. Methods: Clinical, neurological and functional data, including the Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale (GOS), and Functional Independence Measure (FIM) were collected at admission and every 3–5 days until discharge from the intensive/neurointensive care unit. Patients were divided into mobilization and no mobilization groups, depending on whether they received mobilization. Data were analysed by intragroup and intergroup analysis using a multilevel regression model. Results: Sixty-eight patients were included in the mobilization group. At discharge, both groups showed significant improvements in GCS, DRS, LCF and ERBI scores. The mobilization group showed significantly better improvements in FIM cognitive, GOS and ERBI. The patients in the mobilization group stayed longer in the intensive care unit (p = 0.01) and were more likely to be discharged to intensive rehabilitation at a significantly higher rate (p = 0.002) than patients in the no mobilization group. No adverse events were reported in either group. Conclusion: Early mobilization appears to favour the clinical and functional recovery of patients with severe acquired brain injury in the intensive care unit

Microwave Ablation in Intermediate Hepatocellular Carcinoma in Cirrhosis: An Italian Multicenter Prospective Study

Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone. Methods: This multicenter study included 215 cirrhotics (age range: 67-84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3-8 cm) [group A], 70 had 2 nodules (Ø 3-6 cm) [group B] and 36 had 3-5 nodules (Ø 1.5-6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS). Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5-3.5 cm nodules. In nodules >3.5-5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5-8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival. Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome

Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel

MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656-1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517-1.000) and 10-years (AUC: 0.804. 95%CI: 0.517-1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients

Time related variations in stem cell harvesting of umbilical cord blood

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units