A method for dynamic subtraction MR imaging of the liver

BACKGROUND: Subtraction of Dynamic Contrast-Enhanced 3D Magnetic Resonance (DCE-MR) volumes can result in images that depict and accurately characterize a variety of liver lesions. However, the diagnostic utility of subtraction images depends on the extent of co-registration between non-enhanced and enhanced volumes. Movement of liver structures during acquisition must be corrected prior to subtraction. Currently available methods are computer intensive. We report a new method for the dynamic subtraction of MR liver images that does not require excessive computer time. METHODS: Nineteen consecutive patients (median age 45 years; range 37–67) were evaluated by VIBE T1-weighted sequences (TR 5.2 ms, TE 2.6 ms, flip angle 20°, slice thickness 1.5 mm) acquired before and 45s after contrast injection. Acquisition parameters were optimized for best portal system enhancement. Pre and post-contrast liver volumes were realigned using our 3D registration method which combines: (a) rigid 3D translation using maximization of normalized mutual information (NMI), and (b) fast 2D non-rigid registration which employs a complex discrete wavelet transform algorithm to maximize pixel phase correlation and perform multiresolution analysis. Registration performance was assessed quantitatively by NMI. RESULTS: The new registration procedure was able to realign liver structures in all 19 patients. NMI increased by about 8% after rigid registration (native vs. rigid registration 0.073 ± 0.031 vs. 0.078 ± 0.031, n.s., paired t-test) and by a further 23% (0.096 ± 0.035 vs. 0.078 ± 0.031, p < 0.001, paired t-test) after non-rigid realignment. The overall average NMI increase was 31%. CONCLUSION: This new method for realigning dynamic contrast-enhanced 3D MR volumes of liver leads to subtraction images that enhance diagnostic possibilities for liver lesions

Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues

Violent masculinities: Gendered dynamics of policing in Rio de Janeiro

Historically, policing in Rio de Janeiro has been shaped by the equation of racialized violence and masculinity. Attempts to reform the police have paradoxically drawn on forms of male violence that are centered on the rational and professional use of force and on “softer” practices, such as dialogue and collaboration, symbolically coded as feminine. The failure of police reform reflects the cultural salience of understandings of masculinity centered around violence within the police, historical patterns of policing in Rio, and political actors’ strategic cultivation of male violence. Through Rio de Janeiro's failed attempt at police reform, we theorize the relation between racialized state violence, authoritarian political projects, and transgressive forms of male violence, arguing that an important appeal of authoritarianism lies in its promise to carve out a space for performing what we call wild masculinity. [masculinity, race, police, violence, gender, politics, favela, Rio de Janeiro, Brazil]publishedVersio

ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus Document : percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation patients: Indications, patient selection, staff skills, organisation, and training

Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is increasing due to the progressive aging of the population. About 20% of strokes are attributable to AF and AF patients are at five-fold increased risk of stroke. The mainstay of treatment of AF is the prevention of thromboembolic complications with oral anticoagulation therapy. Drug treatment for many years has been based on the use of vitamin K antagonists, but recently newer and safer molecules have been introduced (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban). Despite these advances, many patients still do not receive adequate anticoagulation therapy because of contraindications (relative and absolute) to this treatment. Over the last decade, percutaneous closure of left atrial appendage, main site of thrombus formation during AF, proved effective in reducing thromboembolic complications, thus offering a valid medical treatment especially in patients at increased bleeding risk. The aim of this consensus document is to review the main aspects of left atrial appendage occlusion (selection and multidisciplinary assessment of patients, currently available methods and devices, requirements for centres and operators, associated therapies and follow-up modalities) having as a ground the significant evolution of techniques and the available relevant clinical data

A method for dynamic subtraction MR imaging of the liver.

none6L. MAINARDI; PASSERA KM; LUCESOLI A; POTEPAN P; SETTI E; MUSUMECI RMainardi, Luca; Passera, Km; Lucesoli, A; Potepan, P; Setti, E; Musumeci, R

Intranasal Administration of a TRAIL Neutralizing Monoclonal Antibody Adsorbed in PLGA Nanoparticles and NLC Nanosystems: An In Vivo Study on a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively compromises cognitive functions. Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL), a proinflammatory cytokine belonging to the TNF superfamily, appears to be a key player in the inflammatory/immune orchestra of the AD brain. Despite the ability of an anti-TRAIL monoclonal antibody to reach the brain producing beneficial effects in AD mice, we attempted to develop such a TRAIL-neutralizing monoclonal antibody adsorbed on lipid and polymeric nanocarriers, for intranasal administration, in a valid approach to overcome issues related to both high dose and drug transport across the blood–brain barrier. The two types of nanomedicines produced showed physico-chemical characteristics appropriate for intranasal administration. As confirmed by enzyme-linked immunosorbent assay (ELISA), both nanomedicines were able to form a complex with the antibody with an encapsulation efficiency of ≈99%. After testing in vitro the immunoneutralizing properties of the nanomedicines, the latter were intranasally administered in AD mice. The antibody–nanocarrier complexes were detectable in the brain in substantial amounts at concentrations significantly higher compared to the free form of the anti-TRAIL antibody. These data support the use of nanomedicine as an optimal method for the delivery of the TRAIL neutralizing antibody to the brain through the nose-to-brain route, aiming to improve the biological attributes of anti-TRAIL-based therapy for AD treatment

Impact of multivessel coronary artery disease on early ischemic injury, late clinical outcome, and remodeling in patients with acute myocardial infarction treated by primary coronary angioplasty.

OBJECTIVE: The mechanism through which multivessel coronary artery disease (MVD) adversely affects the outcome of patients with ST-elevation myocardial infarction (STEMI) is poorly characterized. We assessed whether the impact of MVD on outcome of STEMI patients is because of ischemic damage after primary percutaneous coronary intervention (PPCI) or to late ischemic events. METHODS: From August 2005 to 2007, 288 STEMI patients treated by (bare metal) stent-PPCI were prospectively enrolled. The ischemic injury early after PPCI (evaluated by multiparametric approach) and the incidence of late adverse cardiovascular events were compared between the two groups. RESULTS: Compared with single vessel coronary artery disease, MVD patients (n=134) were older, with higher prevalence of diabetes, prior MI, anterior MI and higher collateral score. Myocardial perfusion as assessed by myocardial blush and SigmaST-segment resolution was similar in the two groups as well as the infarct size and microvascular obstruction as assessed by Troponin I and by the delayed enhancement of cardiac magnetic resonance. At clinical (98% complete) and echocardiogaphic (94% complete) follow-up (median 32 months) MVD patients showed a higher incidence of re-MI (6.1 vs. 1.3%), and urgent revascularization (8.3 vs. 2.7%) and worse left ventricular remodeling than single vessel disease patients. At propensity adjusted analysis MVD was an independent predictor of re-MI (odds ratio: 5.7) and ventricular remodeling (odds ratio: 2.2). CONCLUSION: The impact of MVD on clinical outcome and remodeling of STEMI patients is not because of the extent of ischemic damage observed after PPCI, but to recurrent ischemic events during follow-up