Fluorescent 4-amino-1,8-naphthalimide Tröger's bases (TBNaps) possessing (orthogonal) 'α-amino acids', esters and di-peptides and their solvent dependent photophysical properties.

The synthesis of fifteen luminescent bis-naphthalimide based Tröger's bases (TBNaps) derived from 4-amino-1,8-naphthalimide (4-Amino-Nap) precursors is described; these scaffolds possess α-amino acids, esters or di-peptides conjugated at the imide site and show minor fluorescence in aqueous solution while being highly emissive in organic solvents. The investigation shows that these TBNaps possessing ICT excited state properties are capable of generating either positive or negative solvatochromic effects in response to changes in polarity and/or the hydrogen bonding capabilities of the medium.

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents.

The development of functional 1,8-naphthalimide derivatives as DNA targeting, anticancer and cellular imaging agents is a fast growing area and has resulted in several such derivatives entering into clinical trials. This review gives an overview of the many discoveries and the progression of the use of 1,8-naphthalimides as such agents and their applications to date; focusing mainly on mono-, bis-naphthalimide based structures, and their various derivatives (e.g. amines, polyamine conjugates, heterocyclic, oligonucleotide and peptide based, and those based on metal complexes). Their cytotoxicity, mode of action and cell-selectivity are discussed and compared. The rich photophysical properties of the naphthalimides (which are highly dependent on the nature and the substitution pattern of the aryl ring) make them prime candidates as probes as the changes in spectroscopic properties such as absorption, dichroism, and fluorescence can all be used to monitor their binding to biomolecules. This also makes them useful species for monitoring their uptake and location within cells without the use of co-staining. The photochemical properties of the compounds have also been exploited, for example, for photocleavage of nucleic acids and for the destruction of tumour cells.

Prevalence of Preferences for End-of-Life Place of Care and Death Among Patients With Cancer in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

PURPOSE: There is limited information on preferences for place of care and death among patients with cancer in low- and middle-income countries (LMICs). The aim was to report the prevalence and determinants of preferences for end-of-life place of care and death among patients with cancer in LMICs and identify concordance between the preferred and actual place of death. METHODS: Systematic review and meta-analysis guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted. Four electronic databases were searched to identify studies of any design that reported on the preferred and actual place of care and death of patients with cancer in LMICs. A random-effects meta-analysis estimated pooled prevalences, with 95% CI, with subgroup analyses for region and risk of bias. RESULTS: Thirteen studies were included. Of 3,837 patients with cancer, 62% (95% CI, 49 to 75) preferred to die at home; however, the prevalence of actual home death was 37% (95% CI, 13 to 60). Subgroup analyses found that preferences for home as place of death varied from 55% (95% CI, 41 to 69) for Asia to 64% (95% CI, 57 to 71) for South America and 72% (95% CI, 48 to 97) for Africa. The concordance between the preferred and actual place of death was 48% (95% CI, 41 to 55) for South Africa and 92% (95% CI, 88 to 95) for Malaysia. Factors associated with an increased likelihood of preferred home death included performance status and patients with breast cancer. CONCLUSION: There is very little literature from LMICs on the preferences for end-of-life place of care and death among patients with cancer. Rigorous research is needed to help understand how preferences of patients with cancer change during their journey through cancer.

Opioid Therapy for Cancer Pain in Vietnam: Knowledge, Attitudes, and Perceived Barriers Among Health Care Professionals, Policymakers, and Regulators.

PURPOSE: We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS: We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS: Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION: This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.

A Novel Approach to Managing Thirst and Dry Mouth in Palliative Care: A Prospective Randomized Cross-Over Trial.

CONTEXT: Thirst and xerostomia are significant and highly distressing symptoms experienced by patients receiving palliative and end-of-life care. OBJECTIVES: Determine a reduction of thirst intensity and perceptions of dry mouth on a numerical scale following both the experimental intervention (mini mint ice cubes) and control (plain ice chips). METHODS: Cross-over Randomized Controlled Trial (RCT) to assess the effectiveness of novel intervention in the treatment of dry mouth and the sensation of thirst in palliative care patients. RESULTS: Patients rated the severity of their symptoms of dry mouth and thirst using a numeric rating scale (NRS). On commencing the study and preintervention, all patients suffered severe dry mouth and thirst (≥5/10). Mint and plain ice cubes produced improvement of symptoms immediately after interventions. Results from dry mouth ratings show, a decrease of 1.6 points for plain ice cubes (P < 0.0001), on average, ratings for mint ice cubes decreased 3.7 (P < 0.0001). For the sensation of thirst, the plain ice cube intervention group rating decreased 1.7 points (P < 0.006), ratings for mint ice cubes decreased 3.4 points (P < 0.0001). The average decrease in dry mouth and thirst intensity scores from preintervention to postintervention were significantly greater for mint ice cubes (P < 0.05) and 86.6% of patients preferred mint ice cubes. CONCLUSION: This trial found that while usual mouth care and the intervention were both able to reduce the intensity of dry mouth and the sensation of thirst, the mint intervention had a greater response.

Relieving Perception of Thirst and Xerostomia in Patients with Palliative and End-of-life Care Needs: A Rapid Review.

CONTEXT: Thirst and dry mouth are interlinked symptoms that frequently cause significant distress for patients with life-limiting conditions. OBJECTIVES: The objective of this rapid review was to identify and synthesize effective interventions that relieve perceptions of thirst and dry mouth of patients with palliative care and end-of-life care needs. METHODS: Eligible studies were undertaken in clinical settings, with patients experiencing thirst-related distress and/or dry mouth. This review of peer-reviewed literature was conducted following aspects of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. The main outcomes of interest were: 1) efficacy of thirst and dry mouth interventions for patient, and 2) patient, caregiver, and staff acceptability and satisfaction of the interventions. Scientific journal articles were retrieved through searches in electronic databases of MEDLINE (Ovid), CINAHL (EBSCO), and AgeLine (EBSCO). RESULTS: Eleven studies were included for analysis and synthesis of the results. Most studies either focused on a dry mouth intervention or reported dry mouth outcomes within a broader thirst intervention (n = 9/11 studies). Standard oral care was the common intervention type (n = 5/11). All but one dry mouth intervention reported statistical improvement in outcomes of interest. All studies that reported on thirst were conducted in an Intensive Care Unit (ICU) setting (n = 4/4). No studies specifically addressed thirst in patients in specialist palliative care settings. CONCLUSION: Evidence from this review suggests that thirst interventions established within the ICU setting may prove effective for treatment of terminally ill patients receiving specialist palliative care.

A Single Session of a Digital Health Tool-Delivered Exercise Intervention May Provide Immediate Relief from Pelvic Pain in Women with Endometriosis: A Pilot Randomized Controlled Study.

BACKGROUND: Endometriosis is a debilitating chronic condition that is commonly associated with chronic pelvic pain, affecting approximately 10% of women of reproductive age worldwide. The general principle of pain management in this population involves both pharmacological and surgical interventions. There is also increasing interest in the use of exercise as an alternative non-pharmacological analgesic, but adherence and accessibility to face-to-face exercise-delivery modalities are poor. This study aims to determine the immediate impact of a single session of 'supervised' telehealth-delivered exercise compared to 'self-managed' virtual reality (VR)-delivered exercise on pelvic pain associated with endometriosis. METHODS: Twenty-two women experiencing pelvic pain due to endometriosis were included and randomized into three groups: (i) VR-delivered exercise group (n = 8); (ii) telehealth-delivered exercise group (n = 8); and (iii) control group (n = 6). The visual analogue scale (VAS) was used to assess the severity of pelvic pain. RESULTS: There was no statistically significant between-group difference (p = 0.45) in the participants' pain score following a single session of the study interventions (VR or telehealth) or the control. However, a 'medium-to-large' group x time interaction effect (η2 = 0.10) was detected, indicating a more favorable pain score change following a single session of telehealth- (pre-post ∆: +10 ± 12 mm) and VR-delivered exercise (pre-post ∆: +9 ± 24 mm) compared to the control group (pre-post ∆: +16 ± 12 mm). CONCLUSIONS: Our study suggests that a single bout of a 'self-managed' VR-delivered exercise may be as efficacious as a single session of 'supervised' telehealth-delivered exercise in providing immediate relief from pelvic pain associated with endometriosis.

NDIS Participants with Psychosocial Disabilities and Life-Limiting Diagnoses: A Scoping Review.

This research aimed to map evidence about system supports and gaps for Australians with psychosocial disabilities and life-limiting diagnoses. A scoping review of available policy documents, academic, and grey literature was completed to discover key characteristics of this concept and provide context around the phenomenon. Our focus was on Australia's National Disability Insurance Scheme (NDIS), a key reform providing support to the disability population nationally. No peer-reviewed or grey literature was retrieved on the phenomena. Therefore, three lines of enquiry were developed: experiences of NDIS participants living with psychosocial disabilities; the death, dying, and palliative care supports and experiences of NDIS participants of any disability type; and the experiences for people living with severe and persistent mental illness (SPMI) and life-limiting diagnoses. Five themes were identified: (1) the person; (2) advocacy; (3) informal supports; (4) formal supports; and (5) existing research. NDIS participants living with SPMI and their informal and formal support systems are still struggling to navigate the NDIS. While there are no specific publications about their end-of-life experiences, people with SPMI often experience poor end-of-life outcomes. Rigorous research into their death, dying, and palliative care experiences is needed to inform improved support to them, including their end-of-life care.

An innovative approach to targeting pain in older people in the acute care setting.

This paper reports the findings of an exploratory pilot study which used mixed methods to determine (a) the feasibility of the study design for a larger multi site project and (b) whether a pain education promotion approach, termed 'Targeting Pain', using a multidisciplinary educational campaign and promotional media such as staff badges and ward signage, improves the detection and management of pain in older people in an acute care setting. Pre and post evaluation surveys and interviews were used to evaluate the approach. Findings showed an increase in pain assessment and documentation of pain by nursing staff, as well as an increase in the prescription of oral analgesics. However, the study indicated that the uptake regarding pain management from the education campaign was different between professional groups. Although there was a positive response by patients and staff to the use of staff badges, the ward signage failed to attract attention. The mixed methods approach used highlighted several areas that need to be improved for the next phase of the study.

Doing clinical research: the challenges and benefits.

The need for research in practice is well documented within nursing and other health care disciplines. This acceptance is predicated on the belief that clinically applied research will inform and improve practice and health service delivery resulting in better outcomes for consumers and their families. Nurses, however, find doing clinical research challenging. This paper describes nurses' experiences of doing clinical research. The main challenges of doing clinical research arise from a culture that prioritises practice where nursing work is core business and there is the need to address immediate and short term goals. There are also problems associated with the use of research language amongst clinical nurses and ambiguity in relation to research role expectations. Lack of support and resources for doing research along with keeping up the momentum for a research project also pose significant challenges. The benefits of doing clinical nursing research include experiential learning that has the potential to lead to practice change and improved patient outcomes that are evidence based.

Selective partial agonism of liver X receptor alpha is related to differential corepressor recruitment.

Classically, activated transcription by nuclear receptors (NRs) is due to a ligand-induced switch from corepressor- to coactivator-bound states. However, coactivators and corepressors recognize overlapping surfaces of liganded and unliganded NRs, respectively. Here we show that, at sufficiently high concentration, the NR corepressor (NCoR) influences the activity of the liver X receptor (LXR) even in the presence of a potent full agonist that destabilizes NCoR binding. Partial agonist ligands that less effectively dissociate NCoR from LXR are even more sensitive to NCoR levels, in a target gene-selective manner. Thus, differential recruitment of NCoR is a major determinant of partial agonism and selective LXR modulation of target genes.

Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction.

Repression of gene transcription by the nuclear receptor Rev-erbalpha plays an integral role in the core molecular circadian clock. We report the crystal structure of a nuclear receptor-co-repressor (N-CoR) interaction domain 1 (ID1) peptide bound to truncated human Rev-erbalpha ligand-binding domain (LBD). The ID1 peptide forms an unprecedented antiparallel beta-sheet with Rev-erbalpha, as well as an alpha-helix similar to that seen in nuclear receptor ID2 crystal structures but out of register by four residues. Comparison with the structure of Rev-erbbeta bound to heme indicates that ID1 peptide and heme induce substantially different conformational changes in the LBD. Although heme is involved in Rev-erb repression, the structure suggests that Rev-erbalpha could also mediate repression via ID1 binding in the absence of heme. The previously uncharacterized secondary structure induced by ID1 peptide binding advances our understanding of nuclear receptor-co-repressor interactions.

A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity.

Histone deacetylase (HDAC) inhibitors perturb the cell cycle and have great potential as anti-cancer agents, but their mechanism of action is not well established. HDACs classically function as repressors of gene expression, tethered to sequence-specific transcription factors. Here we report that HDAC3 is a critical, transcription-independent regulator of mitosis. HDAC3 forms a complex with A-Kinase-Anchoring Proteins AKAP95 and HA95, which are targeted to mitotic chromosomes. Deacetylation of H3 in mitosis requires AKAP95/HA95 and HDAC3 and provides a hypoacetylated H3 tail that is the preferred substrate for Aurora B kinase. Phosphorylation of H3S10 by Aurora B leads to dissociation of HP1 proteins from methylated H3K9 residues on mitotic heterochromatin. This transcription-independent pathway, involving interdependent changes in histone modification and protein association, is required for normal progression through mitosis and is an unexpected target of HDAC inhibitors, a class of drugs currently in clinical trials for treating cancer.