Luminescent Bimetallic IrIII /AuI Peptide Bioconjugates as Potential Theranostic Agents

Diverse iridium peptide bioconjugates and the corresponding iridium/gold bimetallic complexes have been synthesized starting from a cyclometallated carboxylic acid substituted IrIII complex [Ir(ppy)2 (Phen-5-COO)] by solid phase peptide synthesis (SPPS). The selected peptide sequences were an enkephalin derivative Tyr-Gly-Gly-Phe-Leu together with the propargyl-substituted species Tyr-Gly-Pgl-Phe-Leu to allow gold coordination (Pgl: propyrgyl-glycine, HC=C-Gly), and a specific short peptide, Ala-Cys-Ala-Phen, containing a cysteine residue. Introduction of the gold center has been achieved via a click reaction with the alkynyl group leading to an organometallic Au-C(triazole) species, or by direct coordination to the sulfur atom of the cysteine. The photophysical properties of these species revealed predominantly an emission originating from the Ir complex, using mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity. The formation of the peptide bioconjugates caused a systematic redshift of the emission profiles. Lysosomal accumulation was observed for all the complexes, in contrast to the expected mitochondrial accumulation triggered by the gold complexes. Only the cysteine-containing Ir/Au bioconjugate displayed cytotoxic activity. The absence of activity may be related to the lack of endosomal/lysosomal escape for the cationic peptide conjugates. Interestingly, the different coordination sphere of the gold atom may play a crucial role, as the Au-S(cysteine) bond may be more readily cleaved in a biological environment than the Au-C(triazole) bond, and thus the Au fragment could be released from or trapped in the lysosomes, respectively. This work represents a starting point in the development of bimetallic peptide bioconjugates as theranostics and in the knowledge of factors that contribute to anti-proliferative activity

Cross-cultural validity of the Animated Activity Questionnaire for patients with hip and knee osteoarthritis: a comparison between the Netherlands and Brazil

Background: The Animated Activity Questionnaire (AAQ) was developed in the Netherlands to assess activity limitations in individuals with hip/knee osteoarthritis (HKOA). The AAQ is easy to implement and minimizes the disadvantages of questionnaires and performance-based tests by closely mimicking real-life situations. The AAQ has already been cross-culturally validated in six other countries. Objective: To assess the cross-cultural validity, the construct validity, the reliability of the AAQ in a Brazilian sample of individuals with HKOA, and the influence of formal education on the construct validity of the AAQ. Methods: The Brazilian sample (N = 200), mean age 64.4 years, completed the AAQ and the Western Ontario and McMaster Universities Index (WOMAC). A subgroup of participants performed physical function tests and completed the AAQ twice with a one-week interval. The Dutch sample (N = 279) was included to examine Differential Item Functioning (DIF) between the scores obtained in the Netherlands and Brazil. For this purpose, ordinal regression analyses were used to evaluate whether individuals with the same level of activity limitations from the two countries (the Dutch as the reference group) scored similarly in each AAQ item. To evaluate the construct validity, correlation coefficients were calculated between the AAQ, the WOMAC domains, and the performance-based tests. To evaluate reliability, the Cronbach's alpha coeffi-cient, the intraclass correlation coefficient, and the standard error of measurement (SEM) were calculated. Results: The AAQ showed significant correlations with all the WOMAC domains and performance -based tests (rho=0.46-0.77). The AAQ showed high internal consistency (Cronbach's alpha=0.94), excellent test-retest reliability (ICC2,1 = 0.98), and small SEM (2.25). Comparing to the scores from the Netherlands, the AAQ showed DIF in two items, however, they did not impact on the total AAQ score (rho=0.99). Conclusion: Overall, the AAQ showed adequate cross-cultural validity, construct validity, and reliability, which enables its use in Brazil and international/multicenter studies. (c) 2021 Associacao Brasileira de Pesquisa e Pos-Graduacao em Fisioterapia. Published by Elsevier Espana, S.L.U. All rights reserved.Orthopaedics, Trauma Surgery and Rehabilitatio

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset