A Molecular Analysis of the Aminopeptidase P-Related Domain of PID-5 from Caenorhabditis elegans.

A novel protein, PID-5, has been shown to be a requirement for germline immortality and has recently been implicated in RNA-induced epigenetic silencing in the Caenorhabditis elegans embryo. Importantly, it has been shown to contain both an eTudor and aminopeptidase P-related domain. However, the silencing mechanism has not yet been fully characterised. In this study, bioinformatic tools were used to compare pre-existing aminopeptidase P molecular structures to the AlphaFold2-predicted aminopeptidase P-related domain of PID-5 (PID-5 APP-RD). Structural homology, metal composition, inhibitor-bonding interactions, and the potential for dimerisation were critically assessed through computational techniques, including structural superimposition and protein-ligand docking. Results from this research suggest that the metallopeptidase-like domain shares high structural homology with known aminopeptidase P enzymes and possesses the canonical 'pita-bread fold'. However, the absence of conserved metal-coordinating residues indicates that only a single Zn2+ may be bound at the active site. The PID-5 APP-RD may form transient interactions with a known aminopeptidase P inhibitor and may therefore recognise substrates in a comparable way to the known structures. However, loss of key catalytic residues suggests the domain will be inactive. Further evidence suggests that heterodimerisation with C. elegans aminopeptidase P is feasible and therefore PID-5 is predicted to regulate proteolytic cleavage in the silencing pathway. PID-5 may interact with PID-2 to bring aminopeptidase P activity to the Z-granule, where it could influence WAGO-4 activity to ensure the balanced production of 22G-RNA signals for transgenerational silencing. Targeted experiments into APPs implicated in malaria and cancer are required in order to build upon the biological and therapeutic significance of this research.

Inpatient hospice admissions. Who is admitted and why: a mixed-method prospective study.

Background: Over the next two decades, the numbers of people who will need palliative care in the United Kingdom and Ireland is projected to increase. Hospices play a vital role supporting people who require specialist palliative care input through community-based and inpatient palliative care services. Evidence is needed to understand the role of these different services to inform future service development. Objectives: To describe the reasons for admission, and outcomes at the end of the stay, for patients admitted to two hospice inpatient units (IPUs). Design: This was a mixed-methods study using a convergent, parallel mixed-methods design. Methods: We reviewed the case notes of all patients admitted to two hospice inpatient units from July to November 2019; conducted semi-structured interviews with patients and families; as well as brief structured interviews with inpatient unit staff. Results: Two hundred fifty-nine patients were admitted to a hospice IPU, accounting for 276 admissions in total. Overall, 53% were female; median age was 71 years (range: 26-95 years). Most patients (95%) were White British or Scottish, and 95% had a cancer diagnosis. Most patients were admitted from the community, under one-third were admitted from hospital. Most (85%) had previous palliative care involvement. Nearly, half had district nurse support (48%). Worry and anxiety was frequently reported as a reason for admission, alongside physical concerns. Median length of stay was 12 days, and 68% died during their stay. Hospice was recorded as the preferred place of care for 56% of those who died there. Conclusions: Sustained efforts to promote the hospice as place of care for people with conditions other than cancer are needed alongside greater clarity regarding of the role of the hospice IPU, and who would benefit most from IPU support.

A qualitative meta-synthesis of studies of patients' experience of exercise interventions in advanced cancer.

Background: People with advanced cancer often experience reduced functional capacity and quality of life. Research evaluating the potential benefit of exercise programmes for limiting such decline is accumulating. However, an appraisal of the evidence that considers the patient experience of exercise programmes, what mattered to them and what motivated and encouraged them to engage in exercise, has not been published. The aim of this meta-synthesis was to identify, appraise and bring together evidence from qualitative research in this area. Methods: Four databases were searched from 2nd January to 8th January 2023 for relevant studies. Qualitative studies investigating the experience of exercise as an intervention for adults with advanced cancer were included. Major findings and study characteristics were extracted. Findings were summarised, compared, and synthesised using meta-synthesis. Results: Eight studies were eligible and generated seven sub themes which informed the construction of three key themes: (1) Impact of Delivery Method; (2) Emerging Motivation; and (3) Physical Impact. Conclusion: The analysis revealed that exercise has the potential to positively influence all four dimensions of well-being: physical, psychological, social, and spiritual, for people with advanced cancer. Future research is required to consider the differential impact that the type, volume, and duration of exercise may have on the exercise experience for this patient group.

Rapid investigation of BA.4/BA.5 cases in France.

Aim: We aimed to describe the characteristics of individuals infected by BA.4 or BA.5 in France in comparison to BA.1, and analyze the factors associated with hospitalization among BA.4 and BA.5 cases. Methods: A standardized questionnaire was used to collect information on confirmed and probable Omicron cases. Hospitalization risk factors among BA.4/BA.5 cases were analyzed using Poisson regression. Variables with a p-value below 0.2 in the univariate analysis and a priori confounders were included in the multivariable regression model. Results: The median age of the 301 cases investigated was 47 years and 97% of cases were symptomatic. The most common clinical signs were asthenia/fatigue (75.7%), cough (58.3%), fever (58.3%), headache (52.1%) and rhinorrhea (50.7%). Twelve cases were hospitalized, and 27.1% reported risk factors. No admissions to intensive care and no deaths were reported. Vaccination status was available for 292 cases, 20.9% were unvaccinated, 1.4% had received one dose, 38.3% two doses and 39.4% three doses. Cases presenting at least one risk factor were almost seventeen times more likely to be hospitalized than those with no risk factors (aRR = 16.72 [95% CI2.59-326.86]). Conclusion: Despite the longer duration of and the differences in symptoms and their possible immune escape, BA.4/BA.5 Omicron sub-lineages globally showed no severe clinical presentation. The presence of at least one risk factor for severe disease significantly increased the risk of hospitalization for those infected with BA.4 or BA.5.

Evaluating and volunteering for crowdsourced interventions: Cross-sectional data on COVID-19 safety from a University Survey.

Despite many innovative ideas generated in response to COVID-19, few studies have examined community preferences for these ideas. Our study aimed to determine university community members' preferences for three novel ideas identified through a crowdsourcing open call at the University of North Carolina (UNC) for making campus safer in the pandemic, as compared to existing (i.e. pre-COVID-19) resources. An online survey was conducted from March 30, 2021 -May 6, 2021. Survey participants included UNC students, staff, faculty, and others. The online survey was distributed using UNC's mass email listserv and research directory, departmental listservs, and student text groups. Collected data included participant demographics, COVID-19 prevention behaviors, preferences for finalist ideas vs. existing resources in three domains (graduate student supports, campus tours, and online learning), and interest in volunteering with finalist teams. In total 437 survey responses were received from 228 (52%) staff, 119 (27%) students, 78 (18%) faculty, and 12 (3%) others. Most participants were older than age 30 years (309; 71%), women (332, 78%), and white (363, 83.1%). Five participants (1%) were gender minorities, 66 (15%) identified as racial/ethnic minorities, and 46 (10%) had a disability. Most participants preferred the finalist idea for a virtual campus tour of UNC's lesser-known history compared to the existing campus tour (52.2% vs. 16.0%). For graduate student supports, 41.4% of participants indicated no preference between the finalist idea and existing supports; for online learning resources, the existing resource was preferred compared to the finalist idea (41.6% vs. 30.4%). Most participants agreed that finalists' ideas would have a positive impact on campus safety during COVID-19 (81.2%, 79.6%, and 79.2% for finalist ideas 1, 2 and 3 respectively). 61 (14.1%) participants indicated interest in volunteering with finalist teams. Together these findings contribute to the development and implementation of community-engaged crowdsourced campus safety interventions during COVID-19.

Moral distress amongst palliative care doctors working during the COVID-19 pandemic: A narrative-focussed interview study.

BACKGROUND: Palliative care professionals have had to adapt to rapidly changing COVID-19 restrictions with personal protective equipment and physical distancing measures impacting face-to-face communication with patients and relatives. AIM: To explore the narratives of palliative care doctors working during the pandemic to understand their experiences at a personal and professional level. DESIGN: In-depth narrative interviews were carried out via video call. Interviews were transcribed verbatim and analysed using a joint paradigmatic and narrative approach to elucidate common themes and closely explore individual narratives. SETTING/PARTICIPANTS: Eight palliative care doctors who had worked on a hospice inpatient unit in the UK before and during the pandemic were recruited from two hospices in Scotland. RESULTS: Three intersecting themes are described, the most significant being moral distress. Participants articulated a struggle to reconcile their moral convictions with the restrictions enforced, for example, wanting to provide support to patients through physical proximity but being unable to. To differing degrees, this resulted in internal conflict and emotional distress. Two further themes arose: the first concerned a loss of humanity in interaction and a striving to re-humanise communication through alternative means; the second being a change in staff morale as the pandemic progressed. CONCLUSIONS: Restrictions had a considerable impact on palliative care doctors' ability to communicate with and comfort patients which led to moral distress and contributed to decreasing morale. Future research could explore moral distress in palliative care settings internationally during the pandemic with a view to compare the factors affecting how moral distress was experienced.

Rehabilitation in palliative care: a qualitative study of team professionals.

OBJECTIVES: There has been a recent drive to embed rehabilitation within palliative care. The concept of rehabilitative palliative care has been advocated to help patients preserve function and independence, through greater patient enablement and self-management. Such an approach requires engagement from all members of the palliative care team. There is a lack of understanding of such viewpoints. The objective of this research was to explore hospice-based palliative care professionals' understanding and perceptions of rehabilitation. METHODS: Qualitative semi-structured interviews were conducted. Eighteen hospice-based healthcare professionals were recruited from a hospice in central Scotland. Interviews were audio-recorded, transcribed and thematically analysed. RESULTS: Overall, participants clearly articulated the underlying values and benefits of rehabilitative palliative care. Emphasis was placed on ensuring that rehabilitation was appropriately tailored to each individual patient. There was more ambiguity regarding the pragmatic implementation of rehabilitative palliative care, with a number of barriers and facilitators identified. CONCLUSIONS: The findings suggest that hospice-based palliative care professionals would be receptive to further implementation of rehabilitative palliative care. A lack of conceptual clarity among palliative care professionals may be a barrier to the effective implementation of rehabilitative palliative care. At an organisational level, this would require clarification of the approach, and additional training involving all members of the multidisciplinary team.

Factors influencing adult carer support planning for unpaid caregiving at the end of life in Scotland: Qualitative insights from triangulated interviews and focus groups.

Caring for a relative or friend at the end of life can be rewarding but all-encompassing. These caregivers are often not identified, meaning their diverse needs remain unmet, and the lack of assessment, support and planning increases the likelihood of crisis and burnout. The Carers (Scotland) Act 2016 places responsibility on local authorities to implement such a plan, which will be fast-tracked for carers supporting someone at the end of life. Our research described the factors which might influence this planning, triangulating primary focus groups with 15 carers and secondary qualitative data from transcripts with 30 carers, all of whom who had looked after someone with a terminal illness. Analysis was iterative, and constant comparative analysis of the secondary data informed the primary focus groups. Three main themes were identified; 1. The importance of early identification as a carer to enable timely assessment and support. 2. Carers experience isolation and loneliness which limits opportunities for support. 3. Responding in a timely fashion to carer assessment and support is vital to avoid crises. This research confirms that identifying carers early in the illness trajectory, ideally at diagnosis, is vital to avoid carer burnout. Health and social care providers have a key role in identification and should ensure, where possible, that carer needs are dynamically assessed, supported and documented. Finally, caring does not end after death, it extends into bereavement. Thus, we need to consider system and cultural change to ensure the experiences and needs of carers are addressed and valued.

A randomized, feasibility trial of an exercise and nutrition-based rehabilitation programme (ENeRgy) in people with cancer.

BACKGROUND: Despite rehabilitation being increasingly advocated for people living with incurable cancer, there is limited evidence supporting efficacy or component parts. The progressive decline in function and nutritional in this population would support an approach that targets these factors. This trial aimed to assess the feasibility of an exercise and nutrition based rehabilitation programme in people with incurable cancer. METHODS: We randomized community dwelling adults with incurable cancer to either a personalized exercise and nutrition based programme (experimental arm) or standard care (control arm) for 8 weeks. Endpoints included feasibility, quality of life, physical activity (step count), and body weight. Qualitative and health economic analyses were also included. RESULTS: Forty-five patients were recruited (23 experimental arm, 22 control arm). There were 26 men (58%), and the median age was 78 years (IQR 69-84). At baseline, the median BMI was 26 kg/m2 (IQR: 22-29), and median weight loss in the previous 6 months was 5% (IQR: -12% to 0%). Adherence to the experimental arm was >80% in 16/21 (76%) patients. There was no statistically significant difference in the following between trial arms: step count - median % change from baseline to endpoint, per trial arm (experimental -18.5% [IQR: -61 to 65], control 5% [IQR: -32 to 50], P = 0.548); weight - median % change from baseline to endpoint, per trial arm (experimental 1%[IQR: -3 to 3], control -0.5% [IQR: -3 to 1], P = 0.184); overall quality of life - median % change from baseline to endpoint, per trial arm (experimental 0% [IQR: -20 to 19], control 0% [IQR: -23 to 33], P = 0.846). Qualitative findings observed themes of capability, opportunity, and motivation amongst patients in the experimental arm. The mean incremental cost of the experimental arm versus control was £-319.51 [CI -7593.53 to 6581.91], suggesting the experimental arm was less costly. CONCLUSIONS: An exercise and nutritional rehabilitation intervention is feasible and has potential benefits for people with incurable cancer. A larger trial is now warranted to test the efficacy of this approach.

Virtual reality in hospice: improved patient well-being.

BACKGROUND: Virtual reality (VR) technology as a therapeutic intervention has been gaining attention in healthcare settings in recent years. Studies suggest that using the technology can help alleviate symptoms such as pain and anxiety and induce positive emotions for people in hospital. Managing symptoms and promoting emotional and psychological well-being are core palliative care goals of relieving suffering of people with life-limiting illness. Accordingly, VR may be highly beneficial for use in hospice care yet remains underdeveloped in such settings. This qualitative study aimed to trial the technology and consider what benefits may emerge for hospice in patients. METHODS: A one-off VR session was offered to patients at a hospice in Scotland. Sessions were observed by a researcher and followed by qualitative semi-structured interviews to discuss the experience with those who took part. Interviews were audio recorded, transcribed and thematically analysed. RESULTS: Nineteen hospice patients successfully tried an immersive VR experience. VR sessions were acceptable for people within the hospice environment. The majority of participants enjoyed the experience. Many expressed joy and delight at the process. VR holds possibilities for relieving symptoms such as pain and anxiety frequently experienced by people in hospices. Furthermore, the technology offers the capacity to reconnect with a previous sense of self and to allow respite through the capacity to transcend current reality and connect with another meaningful reality. This exploratory study offers a starting point for larger studies to investigate the utility of VR for hospice patients.

Patient perceptions of their decision to undergo palliative chemotherapy in the Edinburgh Cancer Centre.

BACKGROUND: The decision to undergo chemotherapy for incurable cancer demands informed discussions about the risks and benefits of proposed treatments. Research has shown that many patients have a poor grasp of these factors. METHODS: An evaluation of the patient experience of palliative chemotherapy decision-making was undertaken. Patients with lung or gynaecological cancers were surveyed about their decision, what they understood about its risks and benefits, and how supported they felt. RESULTS: A total of 29 people with lung cancer (n = 21) or gynaecological cancer (n = 8) completed questionnaires. The majority felt sure about their decision, though many were less sure of the risks and benefits of treatment. Unprompted comments revealed significant nuance, including that the decision to undergo chemotherapy may not necessarily have felt like a choice. CONCLUSIONS: Our positive findings may reflect participant selection bias, or could represent genuine comfort in decision-making in Scottish oncology clinics. Further research is needed.

Relational ethics in palliative care research: including a person-centred approach.

The traditional approach to research ethics is to ensure that all ethical issues are adhered to through the scrutiny of research proposals by research ethics committees, themselves sitting within national research governance frameworks. The current approach implies that all potential ethical issues can be considered and mitigated prior to the research. This article is a perspective piece whereby we consider how this approach, on its own, is not enough to ensure ethical practice. We draw attention to the limitations of current ethical procedures in the inherent detachment between the researcher and research participants. We argue that applying a person-centred approach to research ethics allows for contextual and situational factors and places the relationship between research participants and researcher as central.

Experiences of stroke survivors, their families and unpaid carers in goal setting within stroke rehabilitation: a systematic review of qualitative evidence.

OBJECTIVE: The objective of the review was to synthesize the best available qualitative evidence regarding the experiences of stroke survivors, their families and unpaid carers, about goal setting within stroke rehabilitation. INTRODUCTION: Clinical guidelines recommend person-centered goal setting in stroke rehabilitation but many barriers exist to its implementation. Individual differences and preferences, of both the stroke survivor and practitioner, may influence involvement in goal setting. A stroke survivor's relationship with close family members and unpaid carers can be powerful and could influence rehabilitation, recovery and goal setting. INCLUSION CRITERIA: The participants of interest were adults (over 18 years) who had experienced a stroke and undergone rehabilitation, and their families and unpaid carers. The phenomena of interest were the experiences of goal setting within stroke rehabilitation for stroke survivors, their families and unpaid carers. The context was stroke rehabilitation in acute and community hospitals, inpatient rehabilitation units and the community. Studies considered for this review were qualitative primary research studies and the qualitative portion of mixed methods research. METHODS: A three-step search strategy was used to identify English language qualitative primary research studies (both published and unpublished) through November 2017. Two reviewers independently appraised the included studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. Studies were included if they achieved 50% "yes" results for the methodological assessment. Data were extracted from the included papers using the standardized JBI qualitative data extraction tool. Data were synthesized using meta-aggregation. RESULTS: Four studies were included in this review, from which 44 findings were extracted. These were aggregated into 12 categories and four synthesized findings: (1) Person-centered goal setting is possible but often does not occur; (2) Practitioners shape the context of goal setting; (3) Practitioners need to listen to the person and know "who they are" - there is a need for an individualized approach to goal setting; (4) Recovery is ongoing and unpredictable. No findings reporting the experiences of goal setting from the perspective of family or unpaid carers were found, therefore all findings represent stroke survivor experiences. The role of goal setting in self-management could not be extracted from the data. CONCLUSIONS: Person-centered goal setting within stroke rehabilitation is both possible and rewarding but often does not occur. Goal setting contributes to the post-stroke rehabilitation experience and can be positively or negatively influenced by practitioners. Maintaining hope and a sense of forward momentum in recovery after stroke is perceived by stroke survivors as important and could be supported using goal setting that is tailored to the individual's needs and preferences. Future research should focus on refining individualized methods of goal setting in stroke rehabilitation and the role of the practitioner in this, including what skills are needed and how they can be acquired. The identified gaps in the literature about family members' and unpaid carers' experiences, and the role of goal setting in self-management, warrant further research.

Experience of emotion in frail older people towards the end of life: A secondary data analysis.

People are living longer, but with increased age comes greater frailty and multi-morbidity. This secondary data analysis examines transcripts from interviews with 11 frail older people and 6 informal carers to explore emotion in relation to frailty and deteriorating health. Anger and frustration were frequently experienced with declining functional ability; sadness occurred with social isolation, loss of autonomy and independence; anxiety was evident when transition to a care home was discussed; and contentment was described when connecting with others. Reluctant acceptance emerged as a coping strategy. Insights gained from analysing emotion may inform communications training courses for community nurses, though further research is required.

Physical, social, psychological and existential trajectories of loss and adaptation towards the end of life for older people living with frailty: a serial interview study.

BACKGROUND: The experiences of people with cancer and organ disease have been described across different dimensions of need as they approach death. Such information is lacking for frail older people approaching death, but could highlight how a palliative approach might be relevant for this population. METHODS: Cognitively intact, community dwelling adults considered to be moderately or severely frail were recruited from a medical day hospital. Those recruited nominated an informal carer and case-linked professional. Qualitative in-depth serial interviews with older people and their informal carers were conducted over an 18 month period, and single interviews with case-linked healthcare professionals. Interviews were recorded, transcribed and narrative analytical techniques were used to compile case studies. RESULTS: Thirty-four participants (13 patients, 13 informal carers and 8 healthcare professionals) completed 40 individual, 14 joint and 8 professional interviews. Five patients died during the study. The analysis highlighted a dynamic balance between losses and adaptations. Three typical patterns of multi-dimensional change emerged. 1) Maintenance of psychological and existential well-being with a gradual social decline mirroring the physical deterioration. 2) a gradual reduction in both psychological and existential well-being. 3) a marked downturn in social, psychological and existential well-being before death. Frail older people sustained their well-being through maintaining a sense-of-self, garnering support from carers and community structures, and focusing on living from day to day. Their well-being lessened when they lost their sense-of-self, feeling alienated from the world, and confused over the cause of their circumstances. Death remained distant and 'undiagnosed'. Social and community frameworks were essential for supporting their well-being. CONCLUSIONS: Multidimensional end-of-life trajectories for frail older people differed from those with other conditions. Alleviating psychological, social and existential distress should be a priority of care as frail older people reach the end of life. The current palliative care model is problematic for this group. Care should address future concerns and not necessarily involve a focus on death or place of death.

Different Experiences and Goals in Different Advanced Diseases: Comparing Serial Interviews With Patients With Cancer, Organ Failure, or Frailty and Their Family and Professional Carers.

CONTEXT: Quality care for people living with life-limiting illnesses is a global priority. A detailed understanding of the varied experiences of people living and dying with different conditions and their family and professional caregivers should help policymakers and clinicians design and deliver more appropriate and person-centered care. OBJECTIVES: To understand how patients with different advanced conditions and their family and professional caregivers perceive their deteriorating health and the services they need. METHODS: We used a narrative framework to synthesize eight methodologically comparable, longitudinal, and multiperspective interview studies. We compared the end-of-life experiences of people dying from cancer (lung, glioma, and colorectal cancer), organ failure (heart failure, chronic obstructive pulmonary disease, and liver failure), and physical frailty and those of their family and professional caregivers in socioeconomically and ethnically diverse populations in Scotland. RESULTS: The data set comprised 828 in-depth interviews with 156 patients, 114 family caregivers, and 170 health professionals. Narratives about cancer typically had a clear beginning, middle, and an anticipated end. Cancer patients gave a well-rehearsed account of their illness, hoping for recovery alongside fear of dying. In contrast, people with organ failure and their family caregivers struggled to pinpoint when their illness began, or to speak openly about death, hoping instead to avoid further deterioration. Frail older people tended to be frustrated by their progressive loss of independence, fearing dementia or nursing home admission more than dying. CONCLUSION: These contrasting illness narratives affect and shape the experiences, thoughts, and fears of patients and their carers in the last months of life. Palliative care offered by generalists or specialists should be provided more flexibly and equitably, responding to the varied concerns and needs of people with different advanced conditions.

TSH receptor activation and body composition.

The impacts of hyper and hypothyroidism on body composition, i.e. the relative quantity and quality of bone, adipose tissue and muscle, have traditionally been attributed uniquely to abnormal levels of free thyroid hormones. The presence of biologically active TSH receptors in bone, fat and muscle, raises the possibility that both thyroid hormones and TSH contribute to the changes in body composition associated with thyroid disease. This review evaluates the evidence for this in terms of the in vitro experimental approaches applied, data from in vivo sources (i.e. mouse models) and patient-based studies.