Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.Action Medical ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1160

Provisional TAP-Stenting Strategy to Treat Bifurcated Lesions with Drug-Eluting Stents: One-Year Clinical Results of a Prospective Registry

Objective To assess the clinical outcome of unselected patients undergoing drug-eluting stent (DES) implantation on bifurcated lesions using a provisional T And small Protrusion (TAP) stenting strategy Methods Consecutive patients undergoing DES implantation on one major bifurcation lesion were treated by main-vessel (MV) stenting followed (if needed) by side branch (SB) rewiring (with a pullback technique) and kissing balloon SB stenting was performed according to the TAP-technique in selected cases The endpoint of the study was a 12 month incidence of major adverse cardiac events (MACE) defined as cardiac death myocardial infarction (MI) stent thrombosis and target vessel revascularization (TVR) Results The study population included 266 patients (9% unprotected left main) Only 19 patients (7 1%) (with more complex angiographic features) received stents in both the MV and SB using the TAP-technique Overall 22 (8 2%) patients had MACE at 1 year Observed, non-hierarchical MACE were 1 (0 4%) cardiac death 11 (4 1%) MI 2 probable stent thromboses and 12 (4 5%) TVRs Post procedural troponin T increase and adverse events up to 12 months were similar between patients treated by MV stenting only or double stenting Conclusions In unselected patients undergoing DES implantation on bifurcated lesions a provisional TAP-stenting strategy (with a low rate of SB stenting) appears to be safe and effectiv

Outcome of Patients Treated by a Novel Thin-Strut Cobalt-Chromium Stent in the Drug-Eluting Stent Era: Results of the SKICE (Skylor in Real World Practice) Registry

Objectives: To investigate the outcome of patients undergoing percutaneous coronary interventions (PCI) with implantation of a new thin-strut cobalt-chromium bare-metal-stent (BMS) in the drug-eluting-stent (DES) era. Background: Despite the contemporary penetration of DES In the clinical practice, a relevant percentage of patients are still treated by BMS. Data on clinical outcome of novel BMSs are lacking. Methods: This is a sing le-centre-registry enrolling patients treated by Skylor (TM) stent implantation. During the study, the criteria for BMS selection adopted at our institution ("internal" criteria) were as follows: (1) limited compliance to prolonged double antiplatelet therapy, (2) ST-elevation myocardial infarction (STEMI) or saphenous vein grafts (SVG) interventions, and (3) in the absence of these conditions, noncomplex (no bifurcations, no chronic total occlusions) lesions considered at low restenosis risk on the basis of arbitrary angiographic criteria (short lesions, large vessels). Primary and secondary end-points were respectively major adverse cardiovascular events (MACE) and target vessel failure (TVF) up to 9-month. Results: A total of 150 patients were treated with Skylor (TM) stent on 169 lesions. At 9-month follow-up, MACE occurred in 12 patients (8.0%) and TVF in 21 lesions (12.4%). By multivariable analysis, the predictors of MACE were Euroscore >= 9 and ejection fraction < 30% while the predictors of TVF were the absence of the angiographic criteria of low restenosis risk and ejection fraction < 30%. Conclusions: In the DES era, the use of a last-generation BMS in patients with limited compliance to double antiplatelet therapy, STEMI or SVG interventions, and noncomplex angiographic lesions may be associated with acceptable clinical outcome. (C) 2009 Wiley-Liss, Inc