Predicting binding events in very flexible, allosteric, multi-domain proteins.

Knowledge of the structures formed by proteins and small ligands is of fundamental importance for understanding molecular principles of chemotherapy and for designing new and more effective drugs. Due to the still high costs and to the several limitations of experimental techniques, it is most often desirable to predict these ligand-protein complexes in silico, particularly when screening for new putative drugs from databases of millions of compounds. While virtual screening based on molecular docking is widely used for this purpose, it generally fails in mimicking binding events associated with large conformational changes in the protein, particularly when the latter involve multiple domains. In this work, we describe a new methodology aimed at generating bound-like conformations of very flexible and allosteric proteins bearing multiple binding sites. Validation was performed on the enzyme adenylate kinase (ADK), a paradigmatic example of proteins that undergo very large conformational changes upon ligand binding. By only exploiting the unbound structure and the putative binding sites of the protein, we generated a significant fraction of bound-like structures, which employed in ensemble-docking calculations allowed to find native-like poses of substrates, inhibitors, and catalytically incompetent binders. Our protocol provides a general framework for the generation of bound-like conformations of flexible proteins that are suitable to host different ligands, demonstrating high sensitivity to the fine chemical details that regulate protein's activity. We foresee applications in virtual screening for difficult targets, prediction of the impact of amino acid mutations on structure and dynamics, and protein engineering.

Epidemiology of horse trauma: a literature review.

PURPOSE: Horses are used for many recreational and occupational activities. They are large, strong, temperamental, and unpredictable animals and people involved with them are at risk for injuries, from minor abrasions to severe injuries that may lead to death. This review reports on horse trauma in relation to the characteristics of injured equestrians, characteristics of horse trauma, and clinical outcomes. METHODS: A literature search was conducted from health-related electronic databases to identify studies from 2018 to 2023. The search returned 115 relevant full-text articles but after screening and assessment for eligibility, 39 were included in this review for a detailed examination of horse trauma epidemiology. Most studies were undertaken in the USA and the most used method was a retrospective review of hospital or trauma registry data. RESULTS: There have only been very slight changes in horse trauma numbers and outcomes over the past 5 years. Most injuries often follow falls and kicks. Females in their late-20 s to mid-30 s who are recreational equestrians are the group most represented in the data. The commonest injuries include fractures, and head, thoracic, and abdominal trauma. Most individuals with horse trauma were treated in the Emergency Department and discharged. For the equestrians who were admitted to hospital, around one-third required surgery. Mortality rates are very low. CONCLUSION: The popularity of occupational and recreational horse activities does not seem to wane and horse trauma continues to represent a significant concern for the health system. Health care workers need to be cognizant of the scope of trauma presentations as the mechanisms of injury can be complicated putting the equestrian at a high risk of associated injuries that may be life-threatening.

Pain Management in the Postoperative Period for People With Dementia: An Integrative Review.

Objective: With the increased global prevalence of older people with dementia, more will present for surgery over the coming decades. Therefore, the objective of this study was to synthesize the existing research about how pain in managed for people with dementia in the postoperative period and discuss the implications for clinical practice. Methods: For this integrative review, the Cumulative Index to Nursing and Allied Health literature, Medline/Pubmed, ProQuest, ERIC, and Health Source Nursing were searched to identify original empirical research published between 2000 and 2021. Tasks were divided between reviewers to ensure independent study selection, data extraction, and risk of bias assessment. Results: Eleven articles were eligible. The evidence is incompletely developed therefore the review focused on pain assessment, the types and amount of pain relief, that people with dementia receive less analgesia than people without dementia and the challenges for effective pain management. Most studies were surgery for hip fracture so there is scope to look at outcomes for other types of surgery. Analgesia was administered but it was noted that even over a 20-year period, people with dementia received less than cognitively intact people. Pain management could have a stronger evidence-base with more psychometric development of pain assessment tools. Challenges are due to the impaired ability of the person with dementia to communicate pain and that clinicians have difficulty understanding pain behavior in people with dementia. Conclusion: Adequate pain management for people with dementia in the postoperative period is important for a faster and better recovery.

Changes in the prevalence of dementia in Australia and its association with geographic remoteness.

BACKGROUND: The exact prevalence of dementia in Australia is ambiguous. Australia is a vast continent with a small population, and 80% of the population live in five cities. This study explores recent changes in the prevalence of dementia. It also investigates geographic remoteness as a potential risk factor for developing dementia. METHODS: Survey of Disability, Ageing and Carers (SDAC), a nationally representative database, was used to conduct this study. A total of 74,862 and 65,487 individuals from 2015 and 2018, respectively, were considered for this study. A multivariable logistic regression model was used to evaluate the association between dementia and geographic remoteness for older adults aged 65 years and over. RESULTS: The results reveal that from 2015 to 2018, the prevalence of dementia among adults aged 65 years and older was higher in 2018 (5,229 per 100,000) than in 2015 (5,099 per 100,000). Significant geographical differences in the prevalence of dementia are observed among Australian adults, and this trend appears to be increasing. Furthermore, the unadjusted model revealed that, in 2015, older adults living in major cities had 1.29 (AOR: 1.29, 95% CI: 1.17-1.41) times higher odds of having dementia compared with their counterparts from outer regional and remote areas. In 2018, the adjusted model found that older adults living in major cities had 1.12 (AOR: 1.12, 95% CI: 1.01-1.25) times elevated odds of having dementia than their peers living in outer regional and remote areas. CONCLUSION: There is a rising prevalence of dementia in Australia. Further investigation is required to identify the causes of this increase. Increased public health initiatives should concentrate on behavioural characteristics and contextual environmental factors to ameliorate this trend.

Rethinking respite in Australia: A naturalistic effect study of a multicomponent community program to promote respite knowledge, attitudes and behaviours of carers of people with dementia.

'Rethink Respite' was a prospective, naturalistic cohort study conducted in the Illawarra-Shoalhaven (NSW, Australia) to improve knowledge, attitudes and uptake of respite strategies in carers of people with dementia. A convenience sample of n = 70 carers were recruited in 2014-15 to establish a baseline for knowledge, attitudes and use of respite for a cohort of carers in the region. Carer perceived need for respite, burden and self-efficacy were also assessed. A co-designed multi-component community-based intervention was subsequently rolled at in the region from 2015 to 2016. The intervention supported: awareness raising media; carer education sessions; access to web and print respite information resources; and an option to participate in a tailored one-on-one in-home coaching program. At program completion, a follow-up survey was administered to the cohort, with n = 44/70 responding. All n = 44 respondents reported participation in and exposure to 'Rethink Respite' media, information and education during the intervention period. Eighteen of the 44 also self-selected to receive the active tailored coaching support. At follow-up, few positive results were reported on the assessed carer variables for the cohort over time. However, post hoc sub-group analyses found those who also self-selected to receive active support (provided through coaching) (n = 18), showed improvements to their respite knowledge, attitudes and self-efficacy (p < .05). Intention to use respite, and levels of personal gain from caring in this sub-group also increased (p < .05). In contrast, carers who only participated in the informational/educational aspects of the program (and did not self-select to the respite coaching), experienced negative changes over time to their respite beliefs and 'role captivity'. Overall, this pilot study suggests that passive respite information and educational strategies are insufficient, without more active supports (tailored respite coaching) to address observed carer decline over time. Future research should seek to replicate these results using a larger sample and an experimental design.

Nonpharmacological Interventions for Anxiety and Dementia in Nursing Homes: A Systematic Review.

Anxiety is a major mental disorder in later life that impacts on activities of daily living and quality of life for adults living with dementia in nursing homes. The aim of this article was to systematically review nonpharmacological interventions for older adults living in nursing homes who experience comorbid anxiety and dementia. METHOD: A systematic literature search was conducted across key databases (Cinahl, ASSIA, Cochrane reviews and trials, psycARTICLES, psycINFO, and PubMed) to identify studies measuring anxiety as an outcome for an intervention for older adults living with dementia in nursing homes, up to December 31, 2017. RESULTS: The search yielded a total of 1,925 articles with 45 articles accessed for full article review. A total of 13 articles were included in this review following quality appraisal based on Cochrane methodology with six different anxiety measures used. The studies included were moderate to high-quality randomized control trials although heterogeneity precluded a combined meta-analysis. CLINICAL IMPLICATIONS: The most common interventions used to address anxiety in this population were music therapy and activity-based interventions although there was limited evidence for the efficacy of either intervention. Little is known about effective nonpharmacological treatment for anxiety for people living with dementia in nursing homes. Further research using consistent measurement tools and time points is required to identify effective interventions to improve the quality of life for people living with both dementia and anxiety in nursing homes.

Spiritual reminiscence therapy for older people with loneliness, anxiety and depression living in a residential aged care facility, Malaysia: A qualitative approach.

OBJECTIVE: To explore how older people with loneliness, anxiety and depression experience a spiritual reminiscence therapy (SRT) program and to explore its acceptability within the Malaysian population. METHODS: Unstructured observations and a focus-group discussion were carried out with 18 participants involved in a six-week SRT program in a residential care facility in Kuala Lumpur. RESULTS: Analysis revealed four themes: (i) Enthusiastic participation; (ii) Connections across boundaries; (iii) Expressing and reflecting; and (iv) Successful use of triggers. CONCLUSIONS: The findings suggest that the process of reminiscence, on which the program was based, was enjoyable for the participants and created opportunities to form connections with other members of the group. The use of relevant triggers in the SRT program that related to Malaysian cultures, ethnicities and religions was helpful to engage the participants and was acceptable across the different religions and ethnicities.

Aquatic exercise for residential aged care adults with dementia: benefits and barriers to participation.

BACKGROUND: Pilot work by our group has demonstrated that aquatic exercise has valuable functional and psychosocial benefits for adults living in the residential aged care setting with dementia. The aim of the currents study was to advance this work by delivering the Watermemories Swimming Club aquatic exercise program to a more representative population of older, institutionalized adults with dementia. METHODS: The benefits of 12 weeks of twice weekly participation in the Watermemories Swimming Club aquatic exercise program were assessed among an exercise and usual care control group of residential aged care adults with advanced dementia. A battery of physical and psychosocial measures were collected before and after the intervention period, and program implementation was also investigated. RESULTS: Seven residential aged care facilities of 24 approached, agreed to participate and 56 residents were purposefully allocated to exercise or control. Twenty-three participants per group were included in the final analysis. Both groups experienced decreases in skeletal muscle index and lean mass (p < 0.001), but exercise stifled losses in muscle strength and transition into sarcopenic. Behavioral and psychological symptoms of dementia and activities of daily living approached significance (p = 0.06) with positive trends observed across other psychosocial measures. CONCLUSIONS: This study demonstrates the value of exercise participation, and specifically aquatic exercise in comparison to usual care for older, institutionalized adults with advanced dementia. However, it also highlights a number of barriers to participation. To overcome these barriers and ensure opportunity to residents increased provider and sector support is required.

Emotional intelligence and affective events in nurse education: A narrative review.

OBJECTIVE: To investigate the current state of knowledge about emotional intelligence and affective events that arise during nursing students' clinical placement experiences. DESIGN: Narrative literature review. DATA SOURCES: CINAHL, MEDLINE, PsycINFO, Scopus, Web of Science, ERIC and APAIS-Health databases published in English between 1990 and 2016. REVIEW METHODS: Data extraction from and constant comparative analysis of ten (10) research articles. RESULTS: We found four main themes: (1) emotional intelligence buffers stress; (2) emotional intelligence reduces anxiety associated with end of life care; (3) emotional intelligence promotes effective communication; and (4) emotional intelligence improves nursing performance. CONCLUSIONS: The articles we analysed adopted a variety of emotional intelligence models. Using the Ashkanasy and Daus "three-stream" taxonomy (Stream 1: ability models; 2: self-report; 3: mixed models), we found that Stream 2 self-report measures were the most popular followed by Stream 3 mixed model measures. None of the studies we surveyed used the Stream 1 approach. Findings nonetheless indicated that emotional intelligence was important in maintaining physical and psychological well-being. We concluded that developing emotional intelligence should be a useful adjunct to improve academic and clinical performance and to reduce the risk of emotional distress during clinical placement experiences. We call for more consistency in the use of emotional intelligence tests as a means to create an empirical evidence base in the field of nurse education.

Appreciating the work of nurses caring for adults with intellectual disability and mental health issues.

This paper presents findings from a study exploring the nurses' experience of caring for adults with intellectual disability and mental health issues in inpatient settings. Semi structured interviews were undertaken with 13 nurses from various regions of New Zealand. Methods suggested by an Appreciative Inquiry methodology were used to explore the nurses' positive experiences of their role. Interviews were transcribed and analysed using open coding and Leximancer (an online data mining tool) analysis to identify dominant themes in the discourse. Analysis revealed themes around 'Contextualising behaviour', 'Communication', 'Confidence to care' and 'Time'. Participants reflected upon their experiences offering personal interpretations in identifying the aspects of nursing that mattered and that worked. What is shown is that nurses were able to describe a range of creative and adaptive ways of nursing in responding to numerous complex factors they faced in their roles. This suggests a strong foundation on which to advance nursing care in this field.

Psychometric viability of measures of functional performance commonly used for people with dementia: a systematic review of measurement properties.

BACKGROUND: Confidence in findings can only be drawn from measurement tools that have sound psychometric properties for the population with which they are used. Within a dementia specific population, measures of physical function have been poorly justified in exercise intervention studies, with justification of measures based on validity or reliability studies from dissimilar clinical populations, such as people with bronchitis or healthy older adults without dementia. OBJECTIVES: To review the reliability and validity of quantitative measures of pre-identified physical function, as commonly used within exercise intervention literature for adults with dementia. INCLUSION CRITERIA TYPES OF PARTICIPANTS: Participants were adults, aged 65 years and older, with a confirmed medical diagnosis of dementia. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST: n/a TYPES OF STUDIES: Desired studies were observational and cross-sectional and that assessed measures from a pre-identified list of measures of physical function. OUTCOMES: Studies that assessed the psychometric constructs of reliability and validity were targeted. COSMIN taxology was used to define reliability and validity. This included, but were not limited to, Intra-Class Correlations, Kappa, Cronbach's Alpha, Chi Squared, Standard Error of Measurement, Minimal Detectable Change and Limits of Agreement. SEARCH STRATEGY: Published material was sourced from the following four databases: MEDLINE, EMBASE, CINAHL and ISI Web of Science. Grey literature was searched for using ALOIS, Google Scholar and ProQuest. METHODOLOGICAL QUALITY: The COSMIN checklist was used to assess methodological quality of included studies. Assessment was completed by two reviewers independently. DATA EXTRACTION: Reliability and validity data was extracted from included studies using standardized Joanna Briggs Institute data collection forms. Extraction was completed by two reviewers. DATA SYNTHESIS: A narrative synthesis of measurement properties of the tools used to measure physical function was performed. Quantitative meta-analysis was conducted for Intra-Class Correlation Coefficients only. RESULTS: With respect to relative reliability, studies reporting assessed measures had intraclass correlation coefficients greater than 0.71, indicating their suitability for use at a group level. However, a consistent finding among studies that included assessment of absolute reliability was that intra individual variation was too large for meaningful measurement of individuals. This was indicated by large Minimal Detectable Change (MDC) scores. Walk Speed has the smallest reported Mimimal Detectable Change score at 0.11m/s. This represented a change of 35% before statistical variation could be eliminated as the cause for this change. All measures had large MDC values. Walk Speed had the smallest MDC values at 0.11m/s, which represented a necessary change of 35%. Only a limited number of studies assessed the validity of measures. This supports the use of these measures in a very narrow selection of circumstances (see Summary of Findings). CONCLUSIONS: In summary, measures have shown appropriate levels of relative reliability. This supports their use at the group level. However, large levels of intra-individual variation undermine their applicability at the individual level. Limited studies of validity were available to this review, which limits a conclusion on whether measures are valid for people with dementia.

Mental health inpatient experiences of adults with intellectual disability.

This paper presents findings from a study exploring the mental health inpatient care of people with a dual disability of intellectual disability and mental health issues from the perspective of those people with the dual disability. A mixture of semi-structured interviews and focus group interviews were carried out with nine participants who had been admitted to an inpatient unit for mental health care exploring their experience of care. Interviews were transcribed and analyzed using open coding and Leximancer (an online data mining tool) analysis to identify dominant themes in the discourse. Analysis revealed themes around 'Therapeutic and Meaningful Activity', 'Emotion Focussed Care', and 'Feeling Safe?' Participants were able to identify the aspects of inpatient care that worked for them in terms of coping with time in hospital. This research suggests that there are several factors that should be considered in providing effective mental health inpatient care for people with dual disability. A number of strategies and recommendations for responding to their needs are identified and discussed.

The effectiveness of group reminiscence therapy for loneliness, anxiety and depression in older adults in long-term care: a systematic review.

Loneliness, anxiety and depression are common problems for older adults in long-term care. Reminiscence therapy is a non-pharmacological intervention that may be of some benefit. In comparison to individual reminiscence therapy, group reminiscence therapy is a preferred option when dealing with the resource constraints of long-term care. The aim of this paper was to systematically review the literature in order to explore the effectiveness of group reminiscence therapy for older adults with loneliness, anxiety and depression in long-term care. Results indicated that group reminiscence therapy is an effective treatment for depression in older adults, however to date, there is limited research support for its effectiveness to treat loneliness and anxiety. Further research and an improvement in methodological quality, such as using qualitative and mixed methods approaches, is recommended to help establish an evidence base and provide better understanding of the effectiveness of group reminiscence therapy.