Light chain amyloidosis (AL), the most common systemic amyloidosis, is caused by the overproduction and the aggregation of monoclonal immunoglobulin light chains (LC) in target organs. Due to genetic rearrangement and somatic hypermutation, virtually, each AL patient presents a different amyloidogenic LC. Because of such complexity, the fine molecular determinants of LC aggregation propensity and proteotoxicity are, to date, unclear; significantly, their decoding requires investigating large sets of cases. Aiming to achieve generalizable observations, we systematically characterised a pool of thirteen sequence-diverse full length LCs. Eight amyloidogenic LCs were selected as responsible for severe cardiac symptoms in patients; five non-amyloidogenic LCs were isolated from patients affected by multiple myeloma. Our comprehensive approach (consisting of spectroscopic techniques, limited proteolysis, and X-ray crystallography) shows that low fold stability and high protein dynamics correlate with amyloidogenic LCs, while hydrophobicity, structural rearrangements and nature of the LC dimeric association interface (as observed in seven crystal structures here presented) do not appear to play a significant role in defining amyloid propensity. Based on the structural and biophysical data, our results highlight shared properties driving LC amyloid propensity, and these data will be instrumental for the design of synthetic inhibitors of LC aggregation.

No abstract

Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders that don’t have a direct effect on oral health, but severe difficulties in oral hygiene and dental procedures expose people with ASDs to an increased risk of oral diseases. This RCT aimed to evaluate which pedagogical tool was the best to prepare children with ASDs for their first dental examination, either video or photo aids. Two different criteria were used to evaluate their efficacy: the achieved steps into which the procedure was divided (n = 8), and the level of cooperation according to the Frankl Behavioral Scale. One hundred-thirteen subjects were randomly assigned to the two groups and 84 subjects completed the trial (Video group n = 41; Photo group n = 43). A predictive model for the achievement of the Preliminary (1–4) or Dental (4–8) steps was performed using a multivariate logistic regression procedure. Children in the Video group achieved more steps, but the comparison between groups was statistically significant only for the Preliminary steps (p = 0.04). The percentage of subjects judged as cooperating was similar in the two groups. The results of this study underline that behavioural intervention should be used as an effective strategy to prepare subjects with ASDs for a dental examination.

Background. Light chain amyloidosis (AL) is caused by the overproduction, misfolding and aggregation of immunoglobulin light chains (LCs) that tend to deposit as amyloid fibrils in the cardiac tissue 1. Nowadays, the molecular details underling LCs soluble cardiotoxicity and fibril formation remain to be fully elucidated. It has been suggested a relationship between conformational flexibility and amyloidogenicity, indicating protein thermal stability and dynamics as factors able to influence the complex processes of misfolding and aggregation 2,3. To date, no compelling correlations have been identified between LCs cardiotoxicity and primary sequence. Here we present a pivotal mutagenesis study in which we produce and characterise a mutated variant of the toxic H6 LC (mH6). Our purpose is to abrogate the toxicity typical of H6 yielding to a non-cardiotoxic LC and to understand the biophysical and biochemical changes underlying such loss of toxicity.