Hydrophilic interaction and reversed phase mixed-mode liquid chromatography coupled to high resolution tandem mass spectrometry for polar lipids analysis

A hydrophilic interaction liquid chromatography (HILIC) fused-core column (150 × 2.1 mm ID, 2.7 μm particle size) and a short reversed-phase liquid chromatography (RPLC) column (20 mm × 2.1 mm ID, 1.9 μm) were serially coupled to perform mixed-mode chromatography (MMC) on complex mixtures of phospholipids (PL). Mobile phase composition and gradient elution program were, preliminarily, optimized using a mixture of phosphatidylcholines (PC), phosphatidylethanolamines (PE), their corresponding lyso-forms (LPC and LPE), and sphingomyelins (SM). Thus a mixture of PC extracted from soybean was characterized by MMC coupled to electrospray ionization (ESI) high-resolution Fourier-transform mass spectrometry (FTMS) using an orbital trap analyzer. Several previously undiscovered PC, including positional isomers (i.e. 16:0/19:1 and 19:1/16:0) of PC 35:1 and skeletal isomers (i.e. 18:1/18:2 and 18:0/18:3) of PC 36:3 were identified. Therefore, high-resolution MS/MS spectra unveiled the occurrence of isomers for several overall side chain compositions. The proposed MMC-ESI-FTMS/MS approach revealed an unprecedented capability in disclosing complexity of an actual lipid extract, thus representing a very promising approach to lipidomics

Acute shock efficacy of the subcutaneous implantable cardioverter-defibrillator according to the implantation technique

Background: The traditional technique for subcutaneous implantable cardioverter defibrillator (S-ICD) implantation involves three incisions and a subcutaneous (SC) pocket. An intermuscular (IM) 2-incision technique has been recently adopted. Aims: We assessed acute defibrillation efficacy (DE) of S-ICD (DE ≤65 J) according to the implantation technique. Methods: We analyzed consecutive patients who underwent S-ICD implantation and DE testing at 53 Italian centers. Regression analysis was used to determine the association between DFT and implantation technique. Results: A total of 805 patients were enrolled. Four groups were assessed: IM + 2 incisions (n = 546), SC + 2 incisions (n = 133), SC + 3 incisions (n = 111), and IM + 3 incisions (n = 15). DE was ≤65 J in 782 (97.1%) patients. Patients with DE ≤65 J showed a trend towards lower body mass index (25.1 vs. 26.5; p = .12), were less frequently on antiarrhythmic drugs (13% vs. 26%; p = .06) and more commonly underwent implantation with the 2-incision technique (85% vs. 70%; p = .04). The IM + 2-incision technique showed the lowest defibrillation failure rate (2.2%) and shock impedance (66 Ohm, interquartile range: 57-77). On multivariate analysis, the 2-incision technique was associated with a lower incidence of shock failure (hazard ratio: 0.305; 95% confidence interval: 0.102-0.907; p = .033). Shock impedance was lower with the IM than with the SC approach (66 vs. 70 Ohm p = .002) and with the 2-incision than the 3-incision technique (67 vs. 72 Ohm; p = .006). Conclusions: In a large population of S-ICD patients, we observed a high defibrillation success rate. The IM + 2-incision technique provides lower shock impedance and a higher likelihood of successful defibrillation

Physical activity measured by implanted devices predicts atrial arrhythmias and patient outcome: Results of IMPLANTED (Italian Multicentre Observational Registry on Patients With Implantable Devices Remotely Monitored)

Background--To determine whether daily physical activity (PA), as measured by implanted devices (through accelerometer sensor), was related to the risk of developing atrial arrhythmias during long-term follow-up in a population of heart failure (HF) patients with an implantable cardioverter defibrillator (ICD). Methods and Results--The study population was divided into 2 equally sized groups (PA cutoff point: 3.5 h/d) according to their mean daily PA recorded by the device during the 30- to 60-day period post-ICD implantation. Propensity score matching was used to compare 2 equally sized cohorts with similar characteristics between lower and higher activity patients. The primary end point was time free from the first atrial high-rate episode (AHRE) of duration 656 minutes. Secondary end points were: first AHRE 656 hours, first AHRE 6548 hours, and a combined end point of death or HF hospitalization. Data from 770 patients (65\ub115 years; 66% men; left ventricular ejection fraction 35\ub112%) remotely monitored for a median of 25 months were analyzed. A PA =3.5 h/d was associated with a 38% relative reduction in the risk of AHRE 656 minutes (72-month cumulative survival: 75.0% versus 68.1%; log rank P=0.025), and with a reduction in the risk of AHRE 656 hours, AHRE 6548 hours, and the combined end point of death or HF hospitalization (all P < 0.05). Conclusions--In HF patients with ICD, a low level of daily PA was associated with a higher risk of atrial arrhythmias, regardless of the patients' baseline characteristics. In addition, a lower daily PA predicted death or HF hospitalization

An in vivo humanized model to study homing and sequestration of Plasmodium falciparum transmission stages in the bone marrow

IntroductionRecent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a “niche” for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.MethodsWe report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.ResultsWe demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.DiscussionOur model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role