Cell-penetrating peptides containing 2,5-diketopiperazine (DKP) scaffolds as shuttles for anti-cancer drugs: conformational studies and biological activity.

A series of linear and cyclic peptidomimetics composed of a cell-penetrating peptide and a non-natural, bifunctional 2,5-diketopiperazine scaffold is reported. Conformational studies revealed well-defined helical structures in micellar medium for linear structures, while cyclic peptidomimetics were more flexible. Biological investigations showed higher membrane-activity of cyclic derivatives allowing their use as shuttles for anti-cancer drugs.

Predicting self-esteem in informal caregivers of people with dementia: Modifiable and non-modifiable factors.

While informal caregivers often feel burdened by the care for a person with dementia, they can also experience positive consequences due to caregiving; caregiver gains. One of these, relatively overlooked, caregiver gains is heightened self-esteem. We assessed the predictive ability of non-modifiable (caregiver sociodemographic- and dementia related-) and modifiable (psychological-) factors for caregiver self-esteem). A cross-sectional study in which 201 caregivers, who spent at least eight hours a week on caring for a community-residing person with dementia, completed a semi-structured interview and five questionnaires. One two-block (1: non-modifiable-; 2: modifiable variables) hierarchic multiple regression analysis was used to assess which variables predicted self-esteem. None of the non-modifiable variables significantly predicted self-esteem. Regarding the modifiable variables, depression and relationship quality with the person with dementia significantly predicted self-esteem (adjusted R2 = .460, ß = -.207, p = .015 and ß = .632, p < .001 respectively). Caregivers who experience a better relationship quality with the person with dementia, and fewer depression symptoms, experience a higher level of self-esteem. Interventions focused on heightening self-esteem should strive to optimize these factors to enhance the lives of informal dementia caregivers.

Episodic memory and executive functioning in informal dementia caregivers.

Objectives: Informal dementia caregivers are thought to experience high levels of depression and burden, which can contribute to worse cognitive functioning. However, poorer cognitive functioning in caregivers is not always found. The current study explored whether caregivers perform better, worse, or similar to non-caregivers on tasks for executive functioning and memory. Whether sociodemographic and psychosocial characteristics are associated with caregivers' performance was also assessed.Methods: One hundred forty-five caregivers completed the Letter Fluency and Category Fluency, the Logical Memory test from the WMS-III, and five questionnaires assessing psychological characteristics. Standardized z-scores (based on age, education, and sex) were calculated using data from a matched control group (187 non-caregivers). One sample z-tests were executed to examine if the caregivers' standardized mean z-score significantly deviated from the population mean of z = 0. The z-scores were used as dependent variables in multivariable regression analyses.Results: The caregivers performed significantly better on Logical Memory - Immediate Recall than non-caregivers (z = 2.92, p = .004). The obtained z-scores on the other tasks did not deviate significantly from 0. Male sex and social reliance predicted higher scores on Category Fluency, but the F-test was non-significant, and the explained variance was low (adjusted R2 = .068).Conclusions: We found no evidence for poorer cognitive performance among informal caregivers compared to non-caregivers. Our results suggest that caregiving for a loved one with dementia does not impair the caregivers' episodic memory or executive functioning when measured cross-sectionally.

Empathy in informal dementia caregivers and its relationship with depression, anxiety, and burden.

Background/Objective: Recent interventions aim to heighten informal caregivers' empathy levels assuming that this will lead to better well-being. However, previous studies have explored linear associations between empathy and aspects of well-being and yielded mixed results. We hypothesized that quadratic models may be more fitting to describe these relationships. Method: A cross-sectional study, with two groups (201 informal caregivers, and 187 non-caregivers) was conducted. Participants completed questionnaires on cognitive and affective empathy, and depression, anxiety, and caregiver burden. AN(C)OVA's and multiple hierarchical regression analyses including linear and quadratic terms were used to analyze the data. Results: For caregivers, there was a negative quadratic relationship between depression and cognitive empathy, and a positive linear relationship between anxiety and affective empathy, irrespective of sociodemographic characteristics. For non-caregivers, there were positive quadratic relationships between depression and cognitive and affective empathy, and between anxiety and affective empathy. The empathy levels did not differ between the groups. Conclusions: While caregivers and non-caregivers had the same amount of empathy, the relationships between empathy and depression and anxiety differed between the groups. Interventions for informal caregivers could aim to heighten cognitive empathy and to lower affective empathy to diminish depression and anxiety symptoms.

Antecedentes/Objetivo: Intervenciones recientes tienen como objetivo aumentar los niveles de empatía de cuidadores informales suponiendo que ello mejorará el bienestar. Estudios previos que han explorado las asociaciones lineales entre empatía y bienestar mostraron resultados inconsistentes. Presumimos que los modelos cuadráticos pueden ser más adecuados para describir estas relaciones. Método: Se realizó un estudio transversal con dos grupos (201 cuidadores informales y 187 no cuidadores). Completaron cuestionarios sobre empatía cognitiva y afectiva, depresión, ansiedad y carga del cuidador. Se emplearon AN(C)OVA y análisis de regresión jerárquica múltiple incluyendo términos lineales y cuadráticos. Resultados: En los cuidadores se obtuvo una relación cuadrática negativa entre depresión y empatía cognitiva, y una relación lineal positiva entre ansiedad y empatía afectiva, independientemente de las características sociodemográficas. En los no cuidadores hubo relaciones cuadráticas positivas entre depresión y empatía cognitiva y afectiva, y entre ansiedad y empatía afectiva. Los niveles de empatía no difirieron entre ambos grupos. Conclusiones: Mientras ambos grupos tenían la misma cantidad de empatía, las relaciones de empatía con depresión y ansiedad difirieron entre ellos. Las intervenciones para cuidadores informales podrían apuntar a aumentar la empatía cognitiva y reducir la empatía afectiva para disminuir la depresión y los síntomas de ansiedad.

Empathy in informal dementia caregivers and its relationship with depression, anxiety, and burden / Empatía en cuidadores informales de personas con demencia y su relación con depresión, ansiedad y carga mental

Background/Objective: Recent interventions aim to heighten informal caregivers’ empathy levels assuming that this will lead to better well-being. However, previous studies have explored linear associations between empathy and aspects of well-being and yielded mixed results. We hypothesized that quadratic models may be more fitting to describe these relationships. Method: A cross-sectional study, with two groups (201 informal caregivers, and 187 non-caregivers) was conducted. Participants completed questionnaires on cognitive and affective empathy, and depression, anxiety, and caregiver burden. AN(C)OVA's and multiple hierarchical regression analyses including linear and quadratic terms were used to analyze the data. Results: For caregivers, there was a negative quadratic relationship between depression and cognitive empathy, and a positive linear relationship between anxiety and affective empathy, irrespective of sociodemographic characteristics. For non-caregivers, there were positive quadratic relationships between depression and cognitive and affective empathy, and between anxiety and affective empathy. The empathy levels did not differ between the groups. Conclusions: While caregivers and non-caregivers had the same amount of empathy, the relationships between empathy and depression and anxiety differed between the groups. Interventions for informal caregivers could aim to heighten cognitive empathy and to lower affective empathy to diminish depression and anxiety symptoms

Antecedentes/Objetivo: Intervenciones recientes tienen como objetivo aumentar los niveles de empatía de cuidadores informales suponiendo que ello mejorará el bienestar. Estudios previos que han explorado las asociaciones lineales entre empatía y bienestar mostraron resultados inconsistentes. Presumimos que los modelos cuadráticos pueden ser más adecuados para describir estas relaciones. Método: Se realizó un estudio transversal con dos grupos (201 cuidadores informales y 187 no cuidadores). Completaron cuestionarios sobre empatía cognitiva y afectiva, depresión, ansiedad y carga del cuidador. Se emplearon AN(C)OVA y análisis de regresión jerárquica múltiple incluyendo términos lineales y cuadráticos. Resultados: En los cuidadores se obtuvo una relación cuadrática negativa entre depresión y empatía cognitiva, y una relación lineal positiva entre ansiedad y empatía afectiva, independientemente de las características sociodemográficas. En los no cuidadores hubo relaciones cuadráticas positivas entre depresión y empatía cognitiva y afectiva, y entre ansiedad y empatía afectiva. Los niveles de empatía no difirieron entre ambos grupos. Conclusiones: Mientras ambos grupos tenían la misma cantidad de empatía, las relaciones de empatía con depresión y ansiedad difirieron entre ellos. Las intervenciones para cuidadores informales podrían apuntar a aumentar la empatía cognitiva y reducir la empatía afectiva para disminuir la depresión y los síntomas de ansiedad

The Effectiveness of Psychosocial and Behavioral Interventions for Informal Dementia Caregivers: Meta-Analyses and Meta-Regressions.

BACKGROUND: Many psychosocial and behavioral interventions have been developed for informal dementia caregivers. Because existing meta-analyses only focused on a limited number of interventions and outcomes, how effective these interventions are overall and which interventions components are associated with larger effects has yet to be explored. OBJECTIVE: To provide a comprehensive meta-analysis of the effectiveness of psychosocial and behavioral interventions on burden, depression, anxiety, quality of life, stress, and sense of competence in informal dementia caregivers. In addition, we examined if interventions which utilized more sessions and/or were delivered personally (face-to-face) had larger effect sizes. In exploratory meta-regressions, we examined seven additional moderators. METHODS: The protocol was registered with PROSPERO, number CRD42017062555. We systematically searched the literature to identify controlled trials assessing the effect of psychosocial and behavioral interventions on the six outcome measures, for informal dementia caregivers. We performed six random effects meta-analyses, to assess the pooled effect sizes of the interventions. In addition, we performed separate meta-regressions, for each outcome, for each moderator. RESULTS: The sample consisted of 60 studies. For all outcomes except anxiety, the pooled effects were small and in favor of the intervention group. No moderator was found to systematically predict these effects. There were no indications for publication bias or selection bias based on significance. CONCLUSION: Overall, the interventions yield significant (small) effects, independent of intervention characteristics. Future research should explore options to enhance the effectiveness of interventions aimed at assisting informal caregivers.

Exploring the Role of Solvent on Carbohydrate-Aryl Interactions by Diffusion NMR-Based Studies.

Carbohydrate-protein interactions play an important role in many molecular recognition processes. An exquisite combination of multiple factors favors the interaction of the receptor with one specific type of sugar, whereas others are excluded. Stacking CH-aromatic interactions within the binding site provide a relevant contribution to the stabilization of the resulting sugar-protein complex. Being experimentally difficult to detect and analyze, the key CH-π interaction features have been very often dissected using a variety of techniques and simple model systems. In the present work, diffusion NMR spectroscopy has been employed to separate the components of sugar mixtures in different solvents on the basis of their differential ability to interact through CH-π interactions with one particular aromatic cosolute in solution. The experimental data show that the properties of the solvent did also influence the diffusion behavior of the sugars present in the mixture, inhibiting or improving their separation. Overall, the results showed that, for the considered monosaccharide derivatives, their diffusion coefficient values and, consequently, their apparent molecular sizes and/or shapes depend on the balance between solute/cosolute as well as solute/solvent interactions. Thus, in certain media and in the presence of the aromatic cosolute, the studied saccharides that are more suited to display CH-π interactions exhibited a lower diffusion coefficient than the noncomplexing sugars in the mixture. However, when dissolved in another medium, the interaction with the solvent strongly competes with that of the aromatic cosolute.

Can the Mixed Virtual Reality Simulator Into D'mentia Enhance Empathy and Understanding and Decrease Burden in Informal Dementia Caregivers?

OBJECTIVE: To evaluate whether the mixed virtual reality dementia simulator training Into D'mentia increased informal caregivers' understanding for people with dementia, their empathy, sense of competence, relationship quality with the care receiver, and/or decreased burden, depression, and anxiety. METHODS: A quasi-experimental longitudinal study with an intervention group (n = 145) and a control group (n = 56) was conducted. All participants were informal caregivers of people with dementia. They completed six questionnaires and semi-structured interviews 1 week before as well as 1 week, 2.5 months, and 15 months after the training. Data were analyzed on both group and individual level using linear mixed model analyses and Reliable Change Indices. RESULTS: Eighty-five percent of the participants in the intervention group found the intervention useful; 76% said they had changed their approach to caregiving, and 61% stressed that the intervention had increased their understanding of dementia. No significant differences were found between the two groups over time regarding empathy, sense of competence, relationship quality with the care receiver, burden, depression, and anxiety, at either group or individual level. CONCLUSION: Caregivers indicated that the Into D'mentia intervention improved their understanding of dementia, that they had learned to be more patient, to take things more slowly, and to focus on positive aspects of caregiving. However, no significant change was found on the variables assessed via the questionnaires. Future research can consider enriching this intervention with other aspects such as more educational material, more simulations, and group sessions, tailored to the individual caregiver and his/her situation, and examine whether these new interventions yield change on questionnaires. These new, more personalized interventions for dementia caregivers could help caregivers to better understand the persons with dementia they care for and to ultimately enhance the well-being of both caregivers and persons with dementia.

Testing the effectivity of the mixed virtual reality training Into D'mentia for informal caregivers of people with dementia: protocol for a longitudinal, quasi-experimental study.

INTRODUCTION: Informal caregivers for people with dementia (hereafter: caregivers) often feel (over)burdened by the care for a loved one with dementia, and this can have various deleterious effects on both caregivers and patients. Support for caregivers is urgently needed, and for this reason, a dementia simulator (Into D'mentia) was developed in which caregivers experience what it is like to have dementia. The simulator attempts to heighten caregivers' empathy and understanding for the patient and, in turn, diminish their own caregiver burden. The current study evaluates whether the simulator is effective on a number of outcomes. METHODS AND ANALYSIS: A longitudinal, quasi-experimental study is ongoing in the Netherlands. We aim to recruit 142 caregivers in total divided over two groups: 71 caregivers in the intervention group and 71 caregivers in the control group. All participants will complete interviews and questionnaires at four time points: at baseline, 1 week, 2.5 months and 15 months after the training. The primary outcomes include empathy, caregiver burden, caregiver's sense of competence, social reliance, anxiety, depression and caregivers' subjective and objective health. ETHICS AND DISSEMINATION: This study is being carried out in agreement with the Declaration of Helsinki, and the protocol has been approved by the local ethics committees. REGISTRATION DETAILS: This study is registered with The Netherlands National Trial Register (NNTR5856).