Oxidative conversion of transthyretin in formalin-fixed clinical amyloid samples results in the formation of the His90Asp and His90Asn variants.

Background: Proteomics is routinely used to type clinical amyloid deposits, and offers additional benefit of identifying genetic variants, which can be diagnostically useful. Reviewing the proteomics data for ATTR patients attending our Centre revealed an unusually large number of samples containing a rare pathogenic H90D TTR variant alongside the more common H90N variant.

Methods: These findings raised questions to their source.

Human wild-type and D76N β-microglobulin variants are significant proteotoxic and metabolic stressors for transgenic .

β-microglobulin (β-m) is a plasma protein derived from physiological shedding of the class I major histocompatibility complex (MHCI), causing human systemic amyloidosis either due to persistently high concentrations of the wild-type (WT) protein in hemodialyzed patients, or in presence of mutations, such as D76N β-m, which favor protein deposition in the adulthood, despite normal plasma levels. Here we describe a new transgenic Caenorhabditis elegans () strain expressing human WT β-m at high concentrations, mimicking the condition that underlies dialysis-related amyloidosis (DRA) and we compare it to a previously established strain expressing the highly amyloidogenic D76N β-m at lower concentrations. Both strains exhibit behavioral defects, the severity of which correlates with β-m levels rather than with the presence of mutations, being more pronounced in WT β-m worms.

Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence.

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in 16 patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.

Clinical Amyloid Typing by Proteomics: Performance Evaluation and Data Sharing Between Two Centres.

Amyloidosis is a relatively rare human disease caused by the deposition of abnormal protein fibres in the extracellular space of various tissues, impairing their normal function. Proteomic analysis of patients' biopsies, developed by Dogan and colleagues at the Mayo Clinic, has become crucial for clinical diagnosis and for identifying the amyloid type. Currently, the proteomic approach is routinely used at National Amyloidosis Centre (NAC, London, UK) and Istituto di Tecnologie Biomediche-Consiglio Nazionale delle Ricerche (ITB-CNR, Milan, Italy).

Comparative study of the stabilities of synthetic and natural transthyretin amyloid fibrils.

Systemic amyloidosis caused by extracellular deposition of insoluble fibrils derived from the pathological aggregation of circulating proteins, such as transthyretin, is a severe and usually fatal condition. Elucidation of the molecular pathogenic mechanism of the disease and discovery of effective therapies still represents a challenging medical issue. The preparation of amyloid fibrils that exhibit structural and biochemical properties closely similar to those of natural fibrils is central to improving our understanding of the biophysical basis of amyloid formation and may offer an important tool for drug discovery.

Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre.

Systemic amyloidosis is a serious disease which is caused when normal circulating proteins misfold and aggregate extracellularly as insoluble fibrillary deposits throughout the body. This commonly results in cardiac, renal and neurological damage. The tissue target, progression and outcome of the disease depends on the type of protein forming the fibril deposit, and its correct identification is central to determining therapy.

Pitfalls in the characterization of circulating and tissue-resident human γδ T cells.

Dissection of the role and function of human γδ T cells and their heterogeneous subsets in cancer, inflammation, and auto-immune diseases is a growing and dynamic research field of increasing interest to the scientific community. Therefore, harmonization and standardization of techniques for the characterization of peripheral and tissue-resident γδ T cells is crucial to facilitate comparability between published and emerging research. The application of commercially available reagents to classify γδ T cells, in particular the combination of multiple Abs, is not always trouble-free, posing major demands on researchers entering this field.

Binding of Monovalent and Bivalent Ligands by Transthyretin Causes Different Short- and Long-Distance Conformational Changes.

The wild type protein, transthyretin (TTR), and over 120 genetic TTR variants are amyloidogenic and cause, respectively, sporadic and hereditary systemic TTR amyloidosis. The homotetrameric TTR contains two identical thyroxine binding pockets, occupation of which by specific ligands can inhibit TTR amyloidogenesis in vitro. Ligand binding stabilizes the tetramer, inhibiting its proteolytic cleavage and its dissociation.

The effect of lipedema on health-related quality of life and psychological status: a narrative review of the literature.

Purpose: The aim of this narrative review of the literature was to evaluate and summarize the current literature regarding the effect of lipedema on health-related quality of life (HRQOL) and psychological status.

Methods: The authors collected articles through a search into Medline, Embase, Scopus, Web of Science, Physiotherapy Evidence Database (PEDro), and the Cochrane Review. Search terms used included "Lipoedema," "Lipedema," "psychological status," "Quality of life," "Health related quality of life," and "HRQOL.

Exopolymeric substances (EPS) from Salmonella enterica: polymers, proteins and their interactions with plants and abiotic surfaces.

When Salmonella enterica is not in a planktonic state, it persists in organised communities encased in extracellular polymeric substances (EPS), defined as biofilms. Environmental conditions ultimately dictate the key properties of the biofilms such as porosity, density, water content, charge, sorption and ion exchange properties, hydrophobicity and mechanical stability. S.

Efficacy of ultrasound-guided axillary/subclavian venous approaches for pacemaker and defibrillator lead implantation: a randomized study.

Purpose: Subclavian access is a reliable technique for lead insertion in pacemaker and defibrillator (ICD) implantation, but it is often accompanied by complications. The aim of this study was to compare the efficacy of the ultrasound-guided axillary approach to the subclavian method.

Methods: This randomized comparative study was performed on 174 patients: as a first attempt, 116 patients underwent the ultrasound-guided axillary access and 58 patients underwent the subclavian approach.

Long-term results of hybrid therapy in patients with atrial fibrillation who develop atrial flutter during flecainide infusion.

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.

Is pulmonary vein isolation necessary for curing atrial fibrillation?

Background: Pulmonary veins (PVs) play a pivotal role in initiating and perpetuating atrial fibrillation (AF). We investigated if PV electrical isolation from the left atrium is required for curing AF.

Methods And Result: Fifty-one patients with paroxysmal or persistent AF underwent circumferential radiofrequency ablation of PV ostia performed with an anatomic approach.

Response to flecainide infusion predicts long-term success of hybrid pharmacologic and ablation therapy in patients with atrial fibrillation.

Objectives: We tested the hypothesis that the response to flecainide infusion can identify patients with atrial fibrillation (AF) in whom the hybrid pharmacologic and ablation therapy reduces the recurrences of AF.

Background: Infusion of class IC anti-arrhythmic drugs may promote transformation of AF into atrial flutter. Catheter ablation of atrial flutter has been demonstrated to be highly effective in preventing recurrences of atrial flutter.

Determinants of efficacy of atrial pacing in preventing atrial fibrillation recurrences.

Introduction: Several studies have shown that single or dual site atrial pacing is effective in reducing the frequency of recurrent atrial fibrillation (AF) in selected patients. However, it is still unclear what the best predictors are of long-term efficacy of atrial pacing.

Methods And Results: Forty-seven patients with paroxysmal AF requiring demand pacing underwent electrophysiologic study and dual chamber pacemaker implant.