The RAS-24: Development and validation of an adherence-to-medication scale for severe mental illness patients

Abstract Introduction: Several studies have found that most patients with severe mental illness (SMI) and comorbid (physical) conditions are partially or wholly nonadherent to their medication regimens. Nonadherence to treatment is a serious concern, affecting the successful management of patients with SMIs. Psychiatric disorders tend to worsen and persist in nonadherent patients, worsening their overall health. The study described herein aimed to develop and validate a scale (the Ralat Adherence Scale) to measure nonadherence behaviors in a culturally sensitive way. Materials and Methods: Guided by a previous study that explored the primary reasons for nonadherence in Puerto Rican patients, we developed a pool of 147 items linked to the concept of adherence. Nine experts reviewed the meaning, content, clarity, and relevance of the individual items, and a content validity ratio was calculated for each one. Forty items remained in the scale’s first version. This version was administered to 160 patients (21–60 years old). All the participants had a diagnosis of bipolar disorder, major depressive disorder, or schizoaffective disorder. The STROBE checklist was used as the reporting guideline. Results: The scale had very good internal consistency (Cronbach’s alpha = 0.812). After a factor analysis, the scale was reduced to 24 items; the new scale had a Cronbach’s alpha of 0.900. Conclusions: This adherence scale is a self-administered instrument with very good psychometric properties; it has yielded important information about nonadherence behaviors. The scale can help health professionals and researchers to assess patient adherence or nonadherence to a medication regimen

A cross-kingdom Nudix enzyme that pre-empts damage in thiamin metabolism

Genes specifying the thiamin monophos¬phate phosphatase and adenylated thiazole diphosphatase steps in fungal and plant thiamin biosynthesis remain unknown, as do genes for thia¬min diphosphate (ThDP) hydrolysis in thiamin metabolism. A distinctive Nudix domain fused to thia¬min di¬phos¬phokin¬ase (Tnr3) in Schizo¬sacc¬¬h¬aromyces pombe was evaluated as a candidate for these funct¬ions. Com¬par¬¬ative genomic analysis predicted a role in thiamin metabolism, not biosyn¬th¬esis, because free-standing homologues of this Nudix dom¬ain occur not only in fungi and plants, but also in proteo¬bacteria (whose thiamin biosynthesis pathway has no adenylated thiazole or thiamin monophosph¬ate hydrolysis steps) and animals (which do not make thiamin). Supporting this prediction, recomb¬¬inant Tnr3 and its Saccharo¬myces cerevisiae, Arabid¬opsis, and maize Nudix homo¬logues lacked thiamin monophosphate phos¬phatase activity but were active against ThDP, and up to 60-fold more active against diphos¬ph¬ates of the toxic thiamin degradation pro¬ducts oxy- and oxo¬thi¬amin. Deleti¬ng the S. cere¬visiae Nudix gene (YJR142W) lower¬ed oxythiamin resistance, over-expressing it rais¬ed resist¬ance, and express¬ing its plant or bacterial counterparts restored resist-ance to the YJR142W deletant. By converting the di¬phos¬phates of damaged forms of thiamin to monophosphates, the Tnr3 Nudix domain and its homologues can pre-empt the misincor¬p¬or¬ation of damaged diphosphates into ThDP-de¬pend¬ent enzymes, and the resulting toxicity

The role of copper(II) in the aggregation of human amylin

Amylin is the 37-residue peptide hormone produced by the islet β-cells in the pancreas and the formation of amylin aggregates is strongly associated with β-cells degeneration in type 2 diabetes, as demonstrated by more than 95% of patients exhibiting amylin amyloid upon autopsy. It is widely recognized that metal ions such as copper(II) have been implicated in the aggregation process of amyloidogenic peptides such as Aβ and α-synuclein and there is evidence that also amylin self-assembly is largely affected by copper(II). For this reason, in this work, the role of copper(II) in the aggregation of amylin has been investigated by several different experimental approaches. Mass spectrometric investigations show that copper(II) induces significant changes in the amylin structure which decrease the protein fibrillogenesis as observed by ThT measurements. Accordingly, solid-state NMR experiments together with computational analysis carried out on a model amylin fragment confirmed the non fibrillogenic nature of the copper(II) induced aggregated structure. Finally, the presence of copper(II) is also shown to have a major influence on amylin proneness to be degraded by proteases and cytotoxicity studies on different cell cultures are reported

Characterization of the Arabidopsis thaliana 2-Cys peroxiredoxin interactome

This document is the Accepted Manuscript of the following article: Delphine Cerveau, et al, ‘Characterization of the Arabidopsis thaliana 2-Cys peroxiredoxin interactome’, Plant Science, Vol. 252, pp. 30-41, July 2016, doi: https://doi.org/10.1016/j.plantsci.2016.07.003. This manuscript version is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Peroxiredoxins are ubiquitous thiol-dependent peroxidases for which chaperone and signaling roles havebeen reported in various types of organisms in recent years. In plants, the peroxidase function of thetwo typical plastidial 2-Cys peroxiredoxins (2-Cys PRX A and B) has been highlighted while the otherfunctions, particularly in ROS-dependent signaling pathways, are still elusive notably due to the lack ofknowledge of interacting partners. Using an ex vivo approach based on co-immunoprecipitation of leafextracts from Arabidopsis thaliana wild-type and mutant plants lacking 2-Cys PRX expression followedby mass spectrometry-based proteomics, 158 proteins were found associated with 2-Cys PRXs. Alreadyknown partners like thioredoxin-related electron donors (Chloroplastic Drought-induced Stress Proteinof 32 kDa, Atypical Cysteine Histidine-rich Thioredoxin 2) and enzymes involved in chlorophyll synthe-sis (Protochlorophyllide OxidoReductase B) or carbon metabolism (Fructose-1,6-BisPhosphatase) wereidentified, validating the relevance of the approach. Bioinformatic and bibliographic analyses allowedthe functional classification of the identified proteins and revealed that more than 40% are localized inplastids. The possible roles of plant 2-Cys PRXs in redox signaling pathways are discussed in relation withthe functions of the potential partners notably those involved in redox homeostasis, carbon and aminoacid metabolisms as well as chlorophyll biosynthesis.Peer reviewe

State of the art of immunoassay methods for B-type natriuretic peptides: An update

The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1–32, should reduce the systematic differences between methods and result in better harmonization of results