Loneliness stems from a mismatch between the social relationships one has and those one desires. Loneliness often has severe consequences for individuals and society. Recently, an online adaptation of the friendship enrichment program (FEP) was developed and tested to gain insight in its contribution to the alleviation of loneliness. Three loneliness coping strategies are introduced during the program: network development, adapting relationship standards, and reducing the importance of the discrepancy between actual and desired relationships. Data were collected among 239 participants aged 50–86. Loneliness was measured four times using a multi-item scale, and on various days with a single, direct question. Loneliness assessed with the scale declined during and after the program. Scores on loneliness assessed for a specific day, however, are more ambiguous. Despite the immediate positive effect of conducting assignments, we did not observe a decline in the single loneliness item score over the course of the program. The online FEP seems to reduce loneliness in general, but these effects are not visible on today’s loneliness. Nevertheless, the online intervention to reduce loneliness is a valuable new contribution to the collection of loneliness interventions.

Glutathione S-transferases (GSTs) constitute an important class of phase II (de)toxifying enzymes, catalysing the conjugation of glutathione (GSH) with electrophilic compounds. In the present study, Km, kcat and kcat/Km values for the rat GST 1-1-, 3-3-, 4-4- and 7-7-catalysed conjugation reactions between GSH and a series of 10 different 2-substituted 1-chloro-4-nitrobenzenes, and the second-order rate constants (ks) of the corresponding base-catalysed reactions, were correlated with nine classical physicochemical parameters (electronic, steric and lipophilic) of the substituents and with 16 computer-calculated molecular parameters of the substrates and of the corresponding Meisenheimer complexes with MeS- as a model nucleophile for GS- (charge distributions and several energy values), giving structure–activity relationships. On the basis of an identical dependence of the base-catalysed as well as the GST 1-1- and GST 7-7-catalysed reactions on electronic parameters (among others, Hammett substituent constant σp and charge on p-nitro substituents), and the finding that the corresponding reactions catalysed by GSTs 3-3 and 4-4 depend to a significantly lesser extent on these parameters, it was concluded that the Mu-class GST isoenzymes have a rate-determining transition state in the conjugation reaction between 2-substituted 1-chloro-4-nitrobenzenes and GSH which is different from that of the other two GSTs. Several alternative rate-limiting transition states for GST 3-3 and 4-4 are discussed. Furthermore, based on the obtained structure–activity relationships, it was possible to predict the kcat/Km values of the four GST isoenzymes and the ks of the base-catalysed GSH conjugation of 1-chloro-4-nitrobenzene.

Young carers are children and adolescents who provide care to other family members or friends, taking over responsibilities that are usually associated with adulthood. There is emerging but still scarce knowledge worldwide about the phenomenon of young carers and the impact of a caring role on their health, social and personal development spheres. This paper provides an overview of the main results from the ME-WE project, which is the first European research and innovation project dedicated to adolescent young carers (AYCs) (15–17 years). The project methods relied on three main activities: (1) a systematization of knowledge (by means of a survey to AYCs, country case studies, Delphi study, literature review); (2) the co-design, implementation and evaluation of a primary prevention intervention addressing AYCs’ mental health (by means of Blended Learning Networks and a clinical trial in six European countries); (3) the implementation of knowledge translation actions for dissemination, awareness, advocacy and lobbying (by means of national and international stakeholder networks, as well as traditional and new media). Project results substantially contributed to a better understanding of AYCs’ conditions, needs and preferences, defined tailored support intervention (resilient to COVID-19 related restrictions), and significant improvements in national and European policies for AYCs.

Background Online interventions can be as effective as in-person interventions. However, attrition in online intervention is high and potentially biases the results. More importantly, high attrition rates might reduce the effectiveness of online interventions. Therefore, it is important to discover the extent to which factors affect adherence to online interventions. The setting for this study is the online Friendship Enrichment Program, a loneliness intervention for adults aged 50 years and older. Objective This study examined the contribution of severity of loneliness, coping preference, activating content, and engagement in attrition within an online intervention. Methods Data were collected from 352 participants in an online loneliness intervention for Dutch people aged 50 years and older. Attrition was defined as not completing all 10 intervention lessons. The number of completed lessons was assessed through the management system of the intervention. We tested 4 hypotheses on attrition by applying survival analysis (Cox regression). Results Of the 352 participants who subscribed to the intervention, 46 never started the introduction. The remaining 306 participants were divided into 2 categories: 73 participants who did not start the lessons of the intervention and 233 who started the lessons of the intervention. Results of the survival analysis (n=233) showed that active coping preference (hazard ratio [HR]=0.73), activating content (HR=0.71), and 2 indicators of engagement (HR=0.94 and HR=0.79) lowered attrition. Severity of loneliness was not related to attrition. Conclusions To reduce attrition, developers of online (loneliness) interventions may focus on stimulating active behavior within the intervention.

In the present study, eleven 4-substituted 1-chloro-2-nitrobenzenes were tested for their GSH conjugation capacity when catalyzed by base or rat glutathione S-transferase (GST) 4-4. Kinetic parameters (ks and K(m), kcat, and kcat/K(m)) were determined and subsequently used for the description of structure-activity relationships (SAR's). For this purpose, eight physicochemical parameters (electronic, steric, and lipophilic) of the substituents and five computer-calculated parameters of the substrates (charge distributions and several energy values) were used in regression analyses with the kinetic parameters. The obtained SAR's are compared with corresponding SAR's for the GSH conjugation of 2-substituted 1-chloro-4-nitrobenzenes, previously determined [Van der Aar et al. (1996) Chem. Res. Toxicol. 9, 527-534]. The kinetic parameters of the 4-substituted 1-chloro-2-nitrobenzenes correlated well with the Hammett sigma p- constant; the Hammett sigma p constant corrected for "through resonance", while the corresponding kinetic parameters of the 2-substituted 1-chloro-4-nitrobenzenes did not. The base- and GST 4-4-catalyzed GSH conjugation reactions of 2-substituted 1-chloro-4-nitrobenzenes depend to a different extent on the electronic properties of the ortho substituents, suggesting the involvement of different rate-limiting transition states. The base- and GST 4-4-catalyzed conjugation of 4-substituted 1-chloro-2-nitrobenzenes, however, showed a similar dependence on the electronic properties of the para substituents, indicating that these substrates are conjugated to GSH via a similar transition state. Multiple regression analyses revealed that, besides electronic interactions, also steric and lipophilic restrictions appeared to play an important role in the GST 4-4-catalyzed GSH conjugation of 4-substituted 1-chloro-2-nitrobenzenes. Finally, the 4-substituted 1-chloro-2-nitrobenzenes were also used to extend the previously described substrate model for GST 4-4 [De Groot et al. (1995) Chem. Res. Toxicol. 8, 649-658], by which a specific steric restriction of substrates for GST 4-4 became clear.