Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD)

This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.     

VDR,RANKL and OPG polymorphisms as possible predisposing cofactors of postmenopausal osteoporosis: explorative study in Italian population

Postmenopausal osteoporosis (PO) has a strong genetic component. Presently, the published evidence on the association between the main single-nucleotide polymorphisms (SNPs) of the receptor activator of nuclear factor-kb ligand (RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR) and bone mass density (BMD) are scarce, mostly considering Italian population. This study sought to determine whether OPG (rs2073618), RANKL (rs9525641) and the VDR (rs2228570) SNPs were associated with BMD in a sample of 139 North-Italian postmenopausal women. The allelic distribution of rs9525641 in women with PO or osteopenia (OP?+?OPE group) differed from controls (p?p?相似文献   

Evaluation of the prognostic role of tumour‐associated macrophages in newly diagnosed classical Hodgkin lymphoma and correlation with early FDG‐PET assessment

In Hodgkin Lymphoma (HL), about 20% of patients still have relapsed/refractory disease and late toxic effects rate continue to rise with time. ‘Early FDG‐PET’ and tissue macrophage infiltration (TAM) emerged as powerful prognostic predictors. The primary endpoint was to investigate the prognostic role of both early FDG‐PET and TAM; the secondary endpoint was to test if early FDG‐PET positivity could correlate with high TAM score. A cohort of 200 HL patients was analysed. Induction treatment plan consisted of two to six courses of ABVD and, if indicated, involved field radiation therapy. All patients repeated CT scan and FDG‐PET after two cycles and after the completion of therapy. TAM in diagnostic specimens was determined by immunohistochemistry with a monoclonal antibody (anti‐CD68 KP1). Overall, early FDG‐PET was negative in 163 patients (81.5%) and positive in 37 patients (18.5%), showing a significant correlation with the achievement of CR (p < 0.0001). After a median follow‐up of 40 months, progression free survival (PFS) was significantly better for PET negative patients (p < 0.0001). CD68 expression was low, intermediate or high in 26 (13%), 100 (50%) and 74 (37%) cases, without difference in the distribution between responders and non‐responders. PFS analysis showed no significant difference in any score group. TAM score did not show any correlation with early FDG‐PET result. This study confirms that early FDG‐PET has a high prognostic power, while TAM score does not seem to influence the outcome; in contrast to our original hypothesis, it does not correlate with FDG‐PET assessment. Copyright © 2015 John Wiley & Sons, Ltd.     

Attachment orientations and psychological adjustment of parents of children with cancer: A matched-group comparison

Objective: To investigate the impact of childhood cancer on parents' adult attachment, social support, marital adjustment, anxiety, and depression. Methods: 30 parents of children with childhood cancer and 30 matched controls completed the following questionnaires: Experiences in Close Relationships-Revised, Dyadic Adjustment Scale-4, Multidimensional Scale of Perceived Social Support, State-Trait Anxiety Inventory – form Y, and Beck Depression Inventory. Results: Parents of children with childhood cancer had a significantly lower dyadic adjustment than controls, and higher levels of insecure-avoidant attachment, state anxiety, and depression. Conclusion: It is important for health-care personnel to take into account these parents' propensity to show increased levels of avoidant attachment during children's treatment to foster effective communication and supportive relationships between clinicians, pediatric patients, and parents.     

Hydrolysed Formulas in the Management of Cow’s Milk Allergy: New Insights,Pitfalls and Tips

An allergy to cow’s milk requires the avoidance of cow’s milk proteins and, in some infants, the use of a hypoallergenic formula. This review aims to summarize the current evidence concerning different types of hydrolysed formulas (HF), and recommendations for the treatment of IgE- and non-IgE-mediated cow’s milk allergy and functional gastrointestinal disorders in infancy, for which some dietary intervention and HF may be of benefit to both immune and motor mechanisms. Current guidelines recommend cow’s milk protein (i.e., whey or casein) extensively hydrolysed formula (eHF) as the first choice for cow’s milk allergy treatment, and amino acid formulas for more severe cases or those with reactions to eHF. Rice hydrolysed formulas (rHF) have also become available in recent years. Both eHF and rHF are well tolerated by the majority of children allergic to cow’s milk, with no concerns regarding body growth or adverse effects. Some hydrolysates may have a pro-active effect in modulating the immune system due to the presence of small peptides and additional components, like biotics. Despite encouraging results on tolerance acquisition, evidence is still not conclusive, thus hampering our ability to draw firm conclusions. In clinical practice, the choice of hypoallergenic formula should be based on the infant’s age, the severity, frequency and persistence of symptoms, immune phenotype, growth pattern, formula cost, and in vivo proof of tolerance and efficacy.     

The Emerging Role of Nutraceuticals in Cardiovascular Calcification: Evidence from Preclinical and Clinical Studies

Cardiovascular calcification is the ectopic deposition of calcium-phosphate crystals within the arterial wall and the aortic valve leaflets. This pathological process leads to increased vascular stiffness, reduced arterial elasticity, and aortic valve stenosis, increasing the risk of cardiovascular diseases. Although cardiovascular calcification is an increasing health care burden, to date no medical therapies have been approved for treating or preventing it. Considering the current lack of therapeutic strategies and the increasing prevalence of cardiovascular calcification, the investigation of some nutraceuticals to prevent this pathological condition has become prevalent in recent years. Recent preclinical and clinical studies evaluated the potential anti-calcific role of nutraceuticals (including magnesium, zinc, iron, vitamin K, and phytate) in the progression of vascular calcification, providing evidence for their dietary supplementation, especially in high-risk populations. The present review summarizes the current knowledge and latest advances for nutraceuticals with the most relevant preclinical and clinical data, including magnesium, zinc, iron, vitamin K, and phytate. Their supplementation might be recommended as a cost-effective strategy to avoid nutritional deficiency and to prevent or treat cardiovascular calcification. However, the optimal dose of nutraceuticals has not been identified and large interventional trials are warranted to support their protective effects on cardiovascular disease.     

Electrochemically Synthesized Poly(3-hexylthiophene) Nanowires as Photosensitive Neuronal Interfaces

Poly(3-hexylthiophene) (P3HT) is a hole-conducting polymer that has been intensively used to develop organic optoelectronic devices (e.g., organic solar cells). Recently, P3HT films and nanoparticles have also been used to restore the photosensitivity of retinal neurons. The template-assisted electrochemical synthesis of polymer nanowires advantageously combines polymerization and polymer nanostructuring into one, relatively simple, procedure. However, obtaining P3HT nanowires through this procedure was rarely investigated. Therefore, this study aimed to investigate the template-assisted electrochemical synthesis of P3HT nanowires doped with tetrabutylammonium hexafluorophosphate (TBAHFP) and their biocompatibility with primary neurons. We show that template-assisted electrochemical synthesis can relatively easily turn 3-hexylthiophene (3HT) into longer (e.g., 17 ± 3 µm) or shorter (e.g., 1.5 ± 0.4 µm) P3HT nanowires with an average diameter of 196 ± 55 nm (determined by the used template). The nanowires produce measurable photocurrents following illumination. Finally, we show that primary cortical neurons can be grown onto P3HT nanowires drop-casted on a glass substrate without relevant changes in their viability and electrophysiological properties, indicating that P3HT nanowires obtained by template-assisted electrochemical synthesis represent a promising neuronal interface for photostimulation.     

Electrophysiological effects of ivabradine in dog and human cardiac preparations: potential antiarrhythmic actions

Ivabradine is a novel antianginal agent which inhibits the pacemaker current. The effects of ivabradine on maximum rate of depolarization (V_max), repolarization and spontaneous depolarization have not yet been reported in human isolated cardiac preparations. The same applies to large animals close to human in heart size and spontaneous frequency. Using microelectrode technique action potential characteristics and by applying patch-clamp technique ionic currents were studied. Ivabradine exerted concentration-dependent (0.1–10 μM) decrease in the amplitude of spontaneous diastolic depolarization and reduction in spontaneous rate of firing of action potentials and produced a concentration- and frequency-dependent V_max block in dog Purkinje fibers while action potential duration measured at 50% of repolarization was shortened. In the presence of ivabradine, at 400 ms cycle length, V_max block developed with an onset kinetic rate constant of 13.9 ± 3.2 beat⁻¹ in dog ventricular muscle. In addition to a fast recovery of V_max from inactivation (τ = 41–46 ms) observed in control, a second slow component for recovery of V_max was expressed (offset kinetics of V_max block) having a time constant of 8.76 ± 1.34 s. In dog after attenuation of the repolarization reserve ivabradine moderately but significantly lengthened the repolarization. In human, significant prolongation of repolarization was only observed at 10 μM ivabradine. Ivabradine in addition to the Class V antiarrhythmic effect also has Class I/C and Class III antiarrhythmic properties, which can be advantageous in the treatment of patients with ischemic heart disease liable to disturbances of cardiac rhythm.     

Development of solid nanoparticles based on hydroxypropyl-β-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium

Objectives Nanoparticles were designed for the oral administration and transmucosal colon delivery of drugs. Methods Preparation parameters were studied in order to develop solid pH‐dependent drug‐release nanoparticles, constituted by hydroxypropyl‐β‐cyclodextrin and/or Eudragit^® L100 loaded with diclofenac sodium. Nanoemulsions were prepared by the emulsion‐evaporation method using various homogenizers. Different preparative conditions were tested. The emulsions obtained were analysed in terms of size and then dried to obtain solid nanoparticles which were characterized in vitro (particle size, morphology, dissolution, solid state characterization). The effect of nanoparticles on drug permeation through synthetic membranes, colonic pig mucosa and Caco2 cell line were performed. Toxicity studies were carried out to assess the safety of the raw materials used and the nanosystems produced. Key findings Appropriate parameters to obtain nanoemulsions stable enough to be desiccated were determined: Panda NS100L was the most suitable homogenizer for the preparation; particle size ranged between 100 and 600 nm depending on the production method. Solid nanoparticles were obtained by an exsiccation process, which does not modify the mean size. pH‐dependent drug‐release nanoparticles were obtained. The nanoencapsulation process decreased the crystallinity of the drug. Materials and nanoparticles were highly biocompatible. Transmucosal delivery of drug is dependent on the polymer and the test employed: cyclodextrin improved drug permeation across colonic pig mucosa. Conclusions Formulations containing hydroxypropyl‐β‐cyclodextrin represent new colon‐targeted nanoparticles for transmucosal delivery of drugs.