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Aim. This paper reports an investigation of the effects of the implementation of snoezelen, or multisensory stimulation, on the quality of nursing assistants' behaviour during morning care. Background. Nursing assistants in long-term dementia care are often unaware of the impact of their behaviour on patient functioning. Snoezelen is a psychosocial intervention that might improve the quality of caregiver behaviour by combining a person-centred approach with the integration of sensory stimuli. Methods. A quasi-experimental pre- and post-test design was implemented in 12 wards for older mentally infirm patients at six nursing homes. The experimental group intervention was a 4-day in-house 'snoezelen' training, stimulus preference screening and supervision meetings. The control group received usual nursing home care. The effectiveness of the intervention was studied by analysing 250 video recordings, which were assessed by independent observers using a 4-point measurement scale developed for this study and based on Kitwood's Dialectical Framework. Results. The results showed a statistically significant increase in 'Positive Person Work' and decrease in 'Malignant Social Psychology' (total scores) after the implementation of snoezelen. Nursing assistants in the experimental group also improved by statistically significant amounts on all subitems of 'Positive Person Work'. The mean number of sensory stimuli, offered explicitly, increased. Conclusion. The implementation of snoezelen succeeded in effecting a change to a more person-centred approach during morning care. The results indicate that nursing assistants' behaviour can be positively changed provided that the new care model has been successfully implemented. [ABSTRACT FROM AUTHOR]

Meditopes are cyclic peptides that bind in a specific pocket in the antigen-binding fragment of a therapeutic antibody such as cetuximab. Provided their moderate affinity can be enhanced, meditope peptides could be used as specific non-covalent and paratope-independent handles in targeted drug delivery, molecular imaging, and therapeutic drug monitoring. Here we show that the affinity of a recently reported meditope for cetuximab can be substantially enhanced using a combination of yeast display and deep mutational scanning. Deep sequencing was used to construct a fitness landscape of this protein-peptide interaction, and four mutations were identified that together improved the affinity for cetuximab 10-fold to 15 nm Importantly, the increased affinity translated into enhanced cetuximab-mediated recruitment to EGF receptor-overexpressing cancer cells. Although in silico Rosetta simulations correctly identified positions that were tolerant to mutation, modeling did not accurately predict the affinity-enhancing mutations. The experimental approach reported here should be generally applicable and could be used to develop meditope peptides with low nanomolar affinity for other therapeutic antibodies., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

There is a need for person-centred approaches and empowerment of staff within the residential care for older people; a movement called 'culture change'. There is however no single path for achieving culture change. With the aim of increasing understandings about cultural change processes and the promotion of cultural values and norms associated with person-centred practices, this article presents an action research project set on a unit in the Netherlands providing care for older people with dementia. The project is presented as a case study. This study examines what has contributed to the improvement of participation of older people with dementia in daily occupational and leisure activities according to practitioners. Data was collected by participant observation, interviews and focus groups. The results show that simultaneous to the improvement of the older people's involvement in daily activities a cultural transformation took place and that the care became more person-centred. Spontaneous interactions and responses rather than planned interventions, analysis and reflection contributed to this. Furthermore, it proved to be beneficial that the process of change and the facilitation of that process reflected the same values as those underlying the cultural change. It is concluded that changes arise from dynamic, interactive and non-linear processes which are complex in nature and difficult to predict and to control. Nevertheless, managers and facilitators can facilitate such change by generating movement through the introduction of small focused projects that meet the stakeholders' needs, by creating conditions for interaction and sense making, and by promoting the new desired cultural values.

Background: The sense of home of nursing home residents is a multifactorial phenomenon which is important for the quality of living. This purpose of this study is to investigate the factors influencing the sense of home of older adults residing in the nursing home from the perspective of residents, relatives and care professionals., Methods: A total of 78 participants (n = 24 residents, n = 18 relatives and n = 26 care professionals) from 4 nursing homes in the Netherlands engaged in a qualitative study, in which photography was as a supportive tool for subsequent interviews and focus groups. The data were analyzed based on open ended coding, axial coding and selective coding., Results: The sense of home of nursing home residents is influenced by a number of jointly identified factors, including the building and interior design; eating and drinking; autonomy and control; involvement of relatives; engagement with others and activities; quality of care are shared themes. Residents and relatives stressed the importance of having a connection with nature and the outdoors, as well as coping strategies. Relatives and care professionals emphasized the role the organization of facilitation of care played, as well as making residents feel like they still matter., Conclusions: The sense of home of nursing home residents is influenced by a multitude of factors related to the psychology of the residents, and the social and built environmental contexts. A holistic understanding of which factors influence the sense of home of residents can lead to strategies to optimize this sense of home. This study also indicated that the nursing home has a dual nature as a place of residence and a place where people are supported through numerous care strategies.

Introduction: Losing items is a time-consuming occurrence in nursing homes that is ill described. An explorative study was conducted to investigate which items got lost by nursing home residents, and how this affects the residents and family caregivers. Method: Semi-structured interviews and card sorting tasks were conducted with 12 residents with early-stage dementia and 12 family caregivers. Thematic analysis was applied to the outcomes of the sessions. Results: The participants stated that numerous personal items and assistive devices get lost in the nursing home environment, which had various emotional, practical, and financial implications. Significant amounts of time are spent on trying to find items, varying from 1 hr up to a couple of weeks. Numerous potential solutions were identified by the interviewees. Discussion: Losing items often goes together with limitations to the participation of residents. Many family caregivers are reluctant to replace lost items, as these items may get lost again., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

DNA has emerged as a highly versatile construction material for nanometer-sized structures and sophisticated molecular machines and circuits. The successful application of nucleic acid based systems greatly relies on their ability to autonomously sense and act on their environment. In this feature article, the development of DNA-based strategies to dynamically control protein activity via oligonucleotide triggers is discussed. Depending on the desired application, protein activity can be controlled by directly conjugating them to an oligonucleotide handle, or expressing them as a fusion protein with DNA binding motifs. To control proteins without modifying them chemically or genetically, multivalent ligands and aptamers that reversibly inhibit their function provide valuable tools to regulate proteins in a noncovalent manner. The goal of this feature article is to give an overview of strategies developed to control protein activity via oligonucleotide-based triggers, as well as hurdles yet to be taken to obtain fully autonomous systems that interrogate, process and act on their environments by means of DNA-based protein control.

Purpose. To provide an overview of factors influencing the sense of home of older adults residing in the nursing home. Methods. A systematic review was conducted. Inclusion criteria were (1) original and peer-reviewed research, (2) qualitative, quantitative, or mixed methods research, (3) research about nursing home residents (or similar type of housing), and (4) research on the sense of home, meaning of home, at-homeness, or homelikeness. Results. Seventeen mainly qualitative articles were included. The sense of home of nursing home residents is influenced by 15 factors, divided into three themes: (1) psychological factors (sense of acknowledgement, preservation of one's habits and values, autonomy and control, and coping); (2) social factors (interaction and relationship with staff, residents, family and friends, and pets) and activities; and (3) the built environment (private space and (quasi-)public space, personal belongings, technology, look and feel, and the outdoors and location). Conclusions. The sense of home is influenced by numerous factors related to the psychology of the residents and the social and built environmental contexts. Further research is needed to determine if and how the identified factors are interrelated, if perspectives of various stakeholders involved differ, and how the factors can be improved in practice.

The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py-Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py-Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py-Im polyamides. The effect of Py-Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py-Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py-Im-polyamide conjugates. The practical use of protein-Py-Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established.

DNA-templated reversible assembly of an enzyme-inhibitor complex is presented as a new and highly modular approach to control enzyme activity. TEM1-β-lactamase and its inhibitor protein BLIP were conjugated to different oligonucleotides, resulting in enzyme inhibition in the presence of template strand. Formation of a rigid dsDNA linker upon addition of a complementary target strand disrupts the enzyme-inhibitor complex and results in the restoration of enzyme activity, enabling detection of as little as 2 fmol DNA. The noncovalent assembly of the complex allows easy tuning of target and template strands without changing the oligonucleotide-functionalized enzyme and inhibitor domains. Using a panel of eight different template sequences, restoration of enzyme activity was only observed in the presence of the target viral DNA sequence. The use of stable, well-characterized protein domains and the intrinsic modularity of our system should allow easy integration with DNA/RNA-based logic circuits for applications in biomedicine and molecular diagnostics.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Oligonucleotide-based molecular circuits offer the exciting possibility to introduce autonomous signal processing in biomedicine, synthetic biology, and molecular diagnostics. Here we introduce bivalent peptide-DNA conjugates as generic, noncovalent, and easily applicable molecular locks that allow the control of antibody activity using toehold-mediated strand displacement reactions. Employing yeast as a cellular model system, reversible control of antibody targeting is demonstrated with low nM concentrations of peptide-DNA locks and oligonucleotide displacer strands. Introduction of two different toehold strands on the peptide-DNA lock allowed signal integration of two different inputs, yielding logic OR- and AND-gates. The range of molecular inputs could be further extended to protein-based triggers by using protein-binding aptamers., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The quality of the built environment can impact the quality of life and the sense of home of nursing home residents. This study investigated (1) which factors in the physical and social environment correlate with the sense of home of the residents and (2) which environmental factors are most meaningful. Twelve participants engaged in a qualitative study, in which photography was as a supportive tool for subsequent interviews. The data were analysed based on the six phases by Braun and Clarke. The four themes identified are (1) the physical view; (2) mobility and accessibility; (3) space, place, and personal belongings; and (4) the social environment and activities. A holistic understanding of which features of the built environment are appreciated by the residents can lead to the design and retrofitting of nursing homes that are more in line with personal wishes.

Although multi-disciplinary cooperation between professionals is a prerequisite to provide integrated care in the community, this seems hard to realise in practice. Yet, little is known about the experiences of professionals who implement it nor about the organisational features professionals identify as empowering during this cooperation process. Therefore, a case study of a multi-disciplinary geriatric team was performed. The data-collection included observations of meetings, in-depth interviews and focus groups with professionals (N = 12). Data were analysed inductively and related to the three organisational levels within the model of organisational empowerment of Peterson and Zimmerman. Signs of empowering organisational features on the intraorganisational level were mutual trust and clear working routines. On the interorganisational level important features included improved linkages between participating organisations and increased insight into each other's tasks. Tensions occurred relating to the inter- and the extraorganisational level. Professionals felt that the commitment of the management of involved organisations should be improved just as the capacity of the team to influence (local) policy. It is recommended that policymakers should not determine the nature of professional cooperation in advance, but to leave that to the local context as well as to the judgement of involved professionals., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Many older people in western countries express a desire to live independently and stay in control of their lives for as long as possible in spite of the afflictions that may accompany old age. Consequently, older people require care at home and additional support. In some care situations, tension and ambiguity may arise between professionals and clients whose views on risk prevention or health promotion may differ. Following Antonovsky's salutogenic framework, different perspectives between professionals and clients on the pathways that lead to health promotion might lead to mechanisms that explain the origin of these tensions and how they may ultimately lead to reduced responsiveness of older clients to engage in care. This is illustrated with a case study of an older woman living in the community, Mrs Jansen, and her health and social care professionals. The study shows that despite good intentions, engagement, clear division of tasks and tailored care, the responsiveness to receive care can indeed not always be taken for granted. We conclude that to harmonize differences in perspectives between professionals and older people, attention should be given to the way older people endow meaning to the demanding circumstances they encounter (comprehensibility), their perceived feelings of control (manageability), as well as their motivation to comprehend and manage events (meaningfulness). Therefore, it is important that both clients and professionals have an open mind and attempt to understand each others' perspective, and have a dialogue with each other, taking the life narrative of clients into account.

Introduction: This study was designed to test the feasibility and face validity of the composite time trade-off (composite TTO), a new approach to TTO allowing for a more consistent elicitation of negative health state values., Methods: The new instrument combines a conventional TTO to elicit values for states regarded better than dead and a lead-time TTO for states worse than dead., Results: A total of 121 participants completed the composite TTO for ten EQ-5D-5L health states. Mean values ranged from -0.104 for health state 53555 to 0.946 for 21111. The instructions were clear to 98 % of the respondents, and 95 % found the task easy to understand, indicating feasibility. Further, the average number of steps taken in the iteration procedure to achieve the point of indifference in the TTO and the average duration of each task were indicative of a deliberate cognitive process., Conclusion: Face validity was confirmed by the high mean values for the mild health states (>0.90) and low mean values for the severe states (<0.42). In conclusion, this study demonstrates the feasibility and face validity of the composite TTO in a face-to-face standardized computer-assisted interview setting.

We previously reported the development of high affinity Zn(2+) FRET sensors based on the Zn(2+)-mediated interaction between the CXXC motifs present in the copper chaperone proteins ATOX1 and WD4. By systematically substituting several of these cysteines for methionines, we constructed sensor variants that retain a high affinity for Cu(+), while effectively abolishing their ability to form stable tetrahedral Zn(2+) complexes.

This study seeks to explore the sources of strength giving rise to resilience among older people. Twenty-nine in-depth interviews were conducted with older people who receive long-term community care. The interviews were subjected to a thematic content analysis. The findings suggest that the main sources of strength identified among older people were constituted on three domains of analysis; the individual-, interactional and contextual domain. The individual domain refers to the qualities within older people and comprises of three sub-domains, namely beliefs about one's competence, efforts to exert control and the capacity to analyse and understand ones situation. Within these subdomains a variety of sources of strength were found like pride about ones personality, acceptance and openness about ones vulnerability, the anticipation on future losses, mastery by practising skills, the acceptance of help and support, having a balanced vision on life, not adapting the role of a victim and carpe-diem. The interactional domain is defined as the way older people cooperate and interact with others to achieve their personal goals. Sources of strength on this domain were empowering (in)formal relationships and the power of giving. Lastly, the contextual domain refers to a broader political-societal level and includes sources of strength like the accessibility of care, the availability of material resources and social policy. The three domains were found to be inherently linked to each other. The results can be used for the development of positive, proactive interventions aimed at helping older people build on the positive aspects of their lives.

Background: Burden of disease estimates, which combine mortality and morbidity into a single measure, are used increasingly for priority setting in disease control, prevention and surveillance. However, because there is no clear exclusion criterion for highly prevalent minimal disease in burden of disease studies its application may be restricted. The aim of this study was to apply a newly developed relevance criterion based on preferences of a population panel, and to compare burden of disease estimates of five foodborne pathogens calculated with and without application of this criterion., Methods: Preferences for twenty health states associated with foodborne disease were obtained from a population panel (n = 107) with the Visual Analogue Scale and the Time Trade-off (TTO) technique. The TTO preferences were used to derive the relevance criterion: if at least 50% of a panel of judges is willing to trade-off time in order to be restored to full health the health state is regarded as relevant, i.e. TTO median is greater than 0. Subsequently, the burden of disease of each of the five foodborne pathogens was calculated both with and without the relevance criterion., Results: The panel ranked the health states consistently. Of the twenty health states, three did not meet the preference-based relevance criterion. Application of the relevance criterion reduced the burden of disease estimate of all five foodborne pathogens. The reduction was especially significant for norovirus and rotavirus, decreasing with 94% and 78% respectively., Conclusion: Individual preferences elicited with the TTO from a population panel can be used to empirically derive a relevance criterion for burden of disease estimates. Application of this preference-based relevance criterion results in considerable changes in ranking of foodborne pathogens.