Revisiting the Molecular Mechanism of Neurological Manifestations in Antiphospholipid Syndrome: Beyond Vascular Damage

Antiphospholipid syndrome (APS) is a multiorgan disease often affecting the central nervous system (CNS). Typically, neurological manifestations of APS include thrombosis of cerebral vessels leading to stroke and requiring prompt initiation of treatment with antiplatelet drugs or anticoagulant therapy. In these cases, alterations of the coagulation system at various levels caused by multiple effects of antiphospholipid antibodies (aPL) have been postulated to explain the vascular damage to the CNS in APS. However, several nonvascular neurological manifestations of APS have progressively emerged over the past years. Nonthrombotic, immune-mediated mechanisms altering physiological basal ganglia function have been recently suggested to play a central role in the pathogenesis of these manifestations that include, among others, movement disorders such as chorea and behavioral and cognitive alterations. Similar clinical manifestations have been described in other autoimmune CNS diseases such as anti-NMDAR and anti-VGCK encephalitis, suggesting that the spectrum of immune-mediated basal ganglia disorders is expanding, possibly sharing some pathophysiological mechanisms. In this review, we will focus on thrombotic and nonthrombotic neurological manifestations of APS with particular attention to immune-mediated actions of aPL on the vascular system and the basal ganglia

Noncoding RNAs in Duchenne and Becker muscular dystrophies: role in pathogenesis and future prognostic and therapeutic perspectives

Noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs, are key regulators of gene expression at the post-transcriptional level and represent promising therapeutic targets and biomarkers for several human diseases, including Duchenne and Becker muscular dystrophies (DMD/BMD). A role for ncRNAs in the pathogenesis of muscular dystrophies has been suggested, even if it is still incompletely understood. Here, we discuss current progress leading towards the clinical utility of ncRNAs for DMD/BMD. Long and short noncoding RNAs are differentially expressed in DMD/BMD and have a mechanism of action via targeting mRNAs. A subset of muscle-enriched miRNAs, the so-called myomiRs (miR-1, miR-133, and miR-206), are increased in the serum of patients with DMD and in dystrophin-defective animal models. Interestingly, myomiRs might be used as biomarkers, given that their levels can be corrected after dystrophin restoration in dystrophic mice. Remarkably, further evidence demonstrates that ncRNAs also play a role in dystrophin expression; thus, their modulations might represent a potential therapeutic strategy with the aim of upregulating the dystrophin protein in combination with other oligonucleotides/gene therapy approaches

The geometrical nature of optical resonances : from a sphere to fused dimer nanoparticles

We study the electromagnetic response of smooth gold nanoparticles with shapes varying from a single sphere to two ellipsoids joined smoothly at their vertices. We show that the plasmonic resonance visible in the extinction and absorption cross sections shifts to longer wavelengths and eventually disappears as the mid-plane waist of the composite particle becomes narrower. This process corresponds to an increase of the numbers of internal and scattering modes that are mainly confined to the surface and coupled to the incident field. These modes strongly affect the near field, and therefore are of great importance in surface spectroscopy, but are almost undetectable in the far field

Ocular tolerance and efficacy of short-term tamponade with double filling of polydimethyloxane and perfluoro-n-octane

Stefano Zenoni1, Mario R Romano2, Sonia Palmieri1, Natalia Comi1, Edoardo Fiorentini1, Piero Fontana11Ospedali Riuniti di Bergamo, Bergamo, Italy; 2Istituto Clinico Humanitas IRCSS, Rozzano, Milan, ItalyObjective: The aim of the study was to evaluate the ocular tolerance and efficacy of double filling with perfluoro-n-octane (n-C8F18) (PFO) and polydimethyloxane (PDMS) as a temporary vitreous substitute in patients with retinal detachment complicated by proliferative vitreoretinopathy (PVR).Material and methods: Tamponade was performed in 30 eyes of 30 patients by double filling with 30% PFO and 70% PDMS for an average of 23 (standard deviation 2.2) days. The follow-up visits were scheduled 1 week, 1 month, and 3 months after surgery. The main outcome measures were visual acuity, intraocular pressure (IOP), PVR reproliferation, and electrophysiological parameters.Results: The primary success rate was 80% (24/30). Fourteen patients (46.7%) had a postoperative improvement in visual acuity, 12 patients (40.0%) maintained their preoperative visual acuity, and four patients (13.3%) experienced a reduction in visual acuity. The mean postoperative IOP was 19.7 mm Hg (11–32 mm Hg); nine cases (30.0%) developed an IOP increase that was treated with topical drops and/or systemic carbonic anhydrase inhibitors. The electroretinogram (ERG) and the bright flash electroretinogram (bf ERG) parameters showed a statistically significant difference of means between 4- and 8-week follow-up visits.Conclusion: Our experience with double filling in selected cases of retinal detachment has been positive. No electroretinographic signs of retinal toxicity and a low incidence of PVR reproliferation were observed.Keywords: double filling, proliferative vitreo-retinopathy, perfluoro-n-octane, polydimethyloxane, retinal detachment, retinal detachment electrophysiolog

Green tea and pomegranate extract administered during critical moments of the production cycle improves blood antiradical activity and alters cecal microbial ecology of broiler chickens

Phytobiotics are usually tested in feed and throughout the production cycle. However, it could be beneficial to evaluate their effects when administered only during critical moments, such as changes in feeding phases. The aim of the trial was to investigate the effect of a commercial plant extract (PE; IQV-10-P01, InQpharm Animal Health, Kuala Lumpur, Malaysia) on growth performance, blood antiradical activity and cecal microbiome when administered in drinking water to broiler chickens during the post-hatching phase and at each change of diet. In the experiment, 480 1-day-old male broiler chicks were assigned to two groups in a 50-day trial. Broilers received drinking water (C) or drinking water plus PE (T) at a rate of 2 mL/L on days 0 to 4, 10\u201311 and 20\u2013 21. PE did not affect performance and water intake, while total antiradical activity was improved (p < 0.05). A greater abundance of lactic acid bacteria (false discovery rate (FDR) < 0.05) was found in the T group and the result was confirmed at a lower taxonomic level with higher Lactobacillaceae abundance (FDR < 0.05). Our findings suggest that PE administration during critical moments of the production cycle of broiler chickens may exert beneficial effects at a systemic level and on gut microbial ecology

Immunity and inflammation in neurodegenerative diseases.

Immune reactions inside the central nervous system are finely regulated, thanks to the presence of several checkpoints that have the fundamental purpose to preserve this fragile tissue form harmful events. The current knowledge on the role of neuroinflammation and neuro-immune interactions in the fields of multiple sclerosis, Alzheimer's disease and Parkinson's disease is reviewed. Moreover, a focus on the potential role of both active and passive immunotherapy is provided. Finally, we propose a common perspective, which implies that, under pathological conditions, inflammation may exert both detrimental and protective functions, depending on local factors and the timing of immune activation and shutting-off systems

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS