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ObjectiveThe goal of the present study was to deconstruct the 17 treatment arms used in the Early Adult Reduction of weight through LifestYle (EARLY) weight management trials.MethodsIntervention materials were coded to reflect behavioral domains and behavior change techniques (BCTs) within those domains planned for each treatment arm. The analytical hierarchy process was employed to determine an emphasis profile of domains in each intervention.ResultsThe intervention arms used BCTs from all of the 16 domains, with an average of 29.3 BCTs per intervention arm. All 12 of the interventions included BCTs from the six domains of Goals and Planning, Feedback and Monitoring, Social Support, Shaping Knowledge, Natural Consequences, and Comparison of Outcomes; 11 of the 12 interventions shared 15 BCTs in common across those six domains.ConclusionsWeight management interventions are complex. The shared set of BCTs used in the EARLY trials may represent a core intervention that could be studied to determine the required emphases of BCTs and whether additional BCTs add to or detract from efficacy. Deconstructing interventions will aid in reproducibility and understanding of active ingredients.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which mediates staurosporine (STS)--induced cell death. AIF cleavage and translocation to the cytosol is thought to be calpain-1- dependent as calpain inhibitors reduce AIF proteolysis; however, many calpain inhibitors also inhibit matrix metalloproteinase-2 (MMP-2) activity, an intracellular and extracellular protease implicated in apoptosis. Here we investigated whether MMP-2 activity is affected in response to STS and if it contributes to AIF cleavage. Human fibrosarcoma HT1080 cells were treated with STS (0.1 [micro]M, 0.25-24 h). A significant increase in cellular MMP-2 activity was seen by gelatin zymography after a 6 h STS treatment, prior to induction of cell necrosis. Western blot showed the time-dependent appearance of two forms of AIF (~60 and 45 kDa) in the cytosol which were significantly increased at 6 h. Surprisingly, knocking down MMP-2 or inhibiting its activity with MMP-2 preferring inhibitors ARP-100 or ONO-4817, or inhibiting calpain activity with ALLM or PD150606, did not prevent the STS-induced increase in cytosolic AIF. These results show that although STS rapidly increases MMP-2 activity, the cytosolic release of AIF may be independent of the proteolytic activities of MMP-2 or calpain. Key words: matrix metalloproteinase-2, apoptosis-inducing factor, calpain, cytotoxicity, staurosporine, apoptosis. Le facteur induisant l'apoptose (FIA) est une flavoproteine mitochondriale, qui participe a la modulation de la mort cellulaire provoquee par la staurosporine (STS). On pense que le clivage du FIA et sa translocation vers le cytosol sont dependants de la calpaine 1, puisque les inhibiteurs de la calpaine entrainaient une diminution de la proteolyse du FIA. Cependant, beaucoup d'inhibiteurs de la calpaine entrainent aussi une inhibition de l'activite de la metalloproteinase matricielle 2 (MMP-2), une protease intracellulaire et extracellulaire jouant un role dans l'apoptose. Dans les presents travaux, nous avons etudie la possibilite que l'activite de la MMP-2 soit modifiee en reaction a la STS, et aussi qu'elle participe au clivage du FIA. Nous avons expose des cellules de fibrosarcome humain (HT1080) a de la STS (a 0,1 [micro]M, sur 0,25 a 24 heures). Nous avons observe une augmentation marquee de l'activite de la MMP-2 cellulaire a l'aide de la zymographie sur gelatine apres une exposition au STS de 6 heures, avant la production de necrose cellulaire. L'immunobuvardage de Western a revele une apparente proportionnalite entre la duree et deux formes de FIA (environ 60 et 45 kDa) dans le cytosol, avec leur accroissement marque apres 6 heures. Etonnamment, ni la repression (<< knockdown >>) de la MMP-2, ni l'inhibition de son activite a l'aide d'inhibiteurs preferentiels de son activite ARP-100 ou ONO-4817, ni l'inhibition de l'activite de la calpaine a l'aide d'ALLM ou de PD150606, ne parvenaient a prevenir la hausse de FIA cytosolique entrainee par la STS. Ces resultats montrent que meme si la STS entraine une augmentation rapide de l'activite de la MMP-2, la liberation de FIA dans le cytosol pourrait etre independante des activites proteolytiques de la MMP-2 ou de la calpaine. [Traduit par la Redaction] Mots-cles: metalloproteinase matricielle 2, facteur induisant l'apoptose, calpaine, cytotoxicite, staurosporine, apoptose., 1. Introduction Apoptosis-inducing factor (AIF) is a flavoprotein anchored to the mitochondrial inner membrane (Susin et al. 1996). It binds to flavin adenine dinucleotide to exert a NADH oxidase activity [...]

ObjectiveLatinos comprise a growing segment of the caregiver population and vary widely in acculturation, yet little is known regarding how acculturation might affect caregiver stress or intervention outcomes. This study examined the relationship between acculturation and burden, bother, and depression in Latino dementia caregivers at baseline and following an intervention.MethodsThis was a secondary data analysis of 211 Latino caregivers of older adults with dementia from Resources for Enhancing Alzheimer's Caregiver Health (REACH) II, a multisite randomized trial of caregiver interventions. Baseline and follow-up data were used to run mixed-effects models examining the main and moderating effect of acculturation on caregiver stress.ResultsNo significant main effect of acculturation was found for any of the outcome measures, controlling for demographic covariates. Acculturation moderated the effect of the intervention on caregiver burden: those who were more acculturated benefited more from the intervention.ConclusionDifferential acculturation for Latino caregivers was not directly associated with caregiver burden, bother, or depression, but was associated with reducing burden from the intervention. Future research should explore by what mechanism acculturation influences caregiver burden following an intervention.

Anthracyclines, such as doxorubicin, are commonly prescribed antineoplastic agents that cause irreversible cardiac injury. Doxorubicin cardiotoxicity is initiated by increased oxidative stress in cardiomyocytes. Oxidative stress enhances intracellular matrix metalloproteinase-2 (MMP-2) by direct activation of its full-length isoform and (or) de novo expression of an N-terminal-truncated isoform (NTT-MMP-2). As MMP-2 is localized to the sarcomere, we tested whether doxorubicin activates intracellular MMP-2 in neonatal rat ventricular myocytes (NRVM) and whether it thereby proteolyzes two of its identified sarcomeric targets, [alpha]-actinin and troponin I. Doxorubicin increased oxidative stress within 12 h as indicated by reduced aconitase activity. This was associated with a twofold increase in MMP-2 protein levels and threefold higher gelatinolytic activity. MMP inhibitors ARP-100 or ONO-4817 (1 [micro]M) prevented doxorubicin-induced MMP-2 activation. Doxorubicin also increased the levels and activity of MMP-2 secreted into the conditioned media. Doxorubicin upregulated the mRNA expression of both full- length MMP-2 and NTT-MMP-2. [alpha]-actinin levels remained unchanged, whereas doxorubicin downregulated troponin I in an MMPindependent manner. Doxorubicin induces oxidative stress and stimulates a robust increase in MMP-2 expression and activity in NRVM, including NTT-MMP-2. The sarcomeric proteins [alpha]-actinin and troponin I are, however, not targeted by MMP-2 under these conditions.Key words: doxorubicin, oxidative stress, matrix metalloproteinase, cardiac myocyte, sarcomere.Les anthracyclines comme la doxorubicine sont des agents antineoplasiques regulierement prescrits, mais ils entrainent des lesions cardiaques irreversibles. La cardiotoxicite de la doxorubicine commence par l'augmentation du stress oxydatif dans les cardiomyocytes. On sait que le stress oxydatif favorise la metalloproteinase matricielle 2 (MMP-2) intracellulaire par l'intermediaire de l'activation directe de son isoforme de pleine longueur et (ou) de l'expression de novo d'une isoforme tronquee en N-terminal (NTT-MMP-2). Comme la MMP-2 est localisee dans les sarcomeres, nous avons tente de verifier l'hypothese selon laquelle la doxorubicine entraine une activation de la MMP-2 dans les myocytes ventriculaires de rats nouveaunes (MVRNN) et, en consequence, une proteolyse de deux de ses cibles decelees dans les sarcomeres: l'[alpha]-actinine et la troponine I. Comme le montrait une diminution de l'activite de l'aconitase, la doxorubicine a entraine une augmentation du stress oxydatif dans les 12 heures, ce qui etait associe a une augmentation du double des taux proteiques de MMP-2, ainsi qu'a une augmentation du triple de l'activite gelatinolytique. A 1 pM, l'ARP-100 ou l'ONO-4817, deux inhibiteurs des MMP, permettaient de prevenir l'activation de la MMP-2 que provoquait la doxorubicine. La doxorubicine entrainait aussi une augmentation des taux et de l'activite de la MMP-2 secretee dans le milieu conditionne. La doxorubicine entrainait une regulation a la hausse de l'expression de mRNA tant pour la MMP-2 de pleine longueur que pour la NTT-MMP-2. Les taux d'[alpha]-actinine demeuraient inchanges, mais la doxorubicine entrainait une regulation a la baisse de la troponine I de maniere independante des MMP. La doxorubicine entraine un stress oxydatif et stimule une augmentation soutenue de l'expression de la MMP-2 et de l'activite des MVRNN, y compris de la NTT-MMP-2. Par contre, dans ces conditions, la MMP-2 n'a pas pour cible les proteines sarcomeriques que sont l'[alpha]-actinine et la troponine I. [Traduit par la Redaction]Mots-cles: doxorubicine, stress oxydatif, metalloproteinase matricielle, myocyte cardiaque, sarcomere., IntroductionThe therapeutic utility of many anticancer drugs, including anthracyclines such as doxorubicin (DXR), is hampered by their serious cardiotoxic side effects (Singal and Iliskovic 1998; Bloom et al. 2016). Current [...]