End of life care: the importance of advance care planning

Background: Communication about end of life care may involve difficult conversations for patients, family members and health professionals. However, a lack of understanding of a person\u27s wishes about their future care may result in a loss of dignity for the person, and additional distress for their family members and health professionals and burden to the healthcare system. Objective: This article discusses the barriers to advance care planning and provides some guidance for the general practitioner in undertaking advance care planning with patients and their families. Tips for initiating end of life discussions with patients and families utilising the \u27PREPARED\u27 acronym, and ensuring appropriate care delivery are included. Discussion: Involving patients and their family members in advance care planning may be challenging and time consuming for GPs. However, there are a number of resources to support this activity in relation to training, communication support and Medicare item funding

Omega 3 Fatty Acid Inhibition of Inflammatory Cytokine-Mediated Connexin43 Regulation in the Heart

Background: The proinflammatory cytokine $Interleukin-1\beta$ $(IL-1\beta)$, which increases in the heart post myocardial infarction (MI), has been shown to cause loss of Connexin43 (Cx43) function, an event known to underlie formation of the arrhythmogenic substrate. Omega 3 Fatty acids exhibit antiarrhythmic properties and impact $IL-1\beta$ signaling. We hypothesize that Omega-3 fatty acids prevent arrhythmias in part, by inhibiting $IL-1\beta$ signaling thus maintaining functional Cx43 channels. Methods: Rat neonatal myocytes or Madin-Darby Canine Kidney Epithelial (MDCK) cells grown in media in the absence (Ctr) or presence of $30 \mu M$ docosahexaenoic acid (DHA, an Omega-3 Fatty acid) were treated with $0.1 \mu M$ activated $IL-1\beta$. We determined Cx43 channel function using a dye spread assay. Western blot and immunostaining were used to examine Cx43 levels/localization and downstream effectors of $IL-1\beta$. In addition we used a murine model of MI for 24 h to determine the impact of an Omega-3 fatty acid enriched diet on Cx43 levels/localization post MI. Results: $IL-1\beta$ significantly inhibited Cx43 function in Ctr cells $(200.9 \pm 17.7 \mu m [Ctr] vs. 112.8 \pm 14.9 \mu m [0.1 \mu M IL-1\beta], p<0.05)$. However, DHA-treated cells remained highly coupled in the presence of $IL-1\beta$ $[167.9 \pm 21.9 \mu m [DHA] vs. 164.4 \pm 22.3 \mu m [DHA + 0.1 \ muM IL-1\beta], p<0.05, n = 4]$. Additionally, western blot showed that $IL-1\beta$ treatment caused a 38.5% downregulation of Cx43 $[1.00 au [Ctr] vs. 0.615 au (0.1 \mu M IL-1\beta)$ which was completely abolished in DHA-treated cells $(0.935 au [DHA] vs. 1.02 au [DHA + 0.1 \mu M IL-1\beta), p < 0.05, n = 3]$. Examination of the downstream modulator of $IL-1\beta$, $NF\kappa \beta$ showed that while hypoxia caused translocation of $NF\kappa \beta$ to the nucleus, this was inhibited by DHA. Additionally we found that a diet enriched in Omega-3 Fatty acids inhibited lateralization of Cx43 in the post-MI murine heart as well as limited activation of fibroblasts which would lead to decreased fibrosis overall. Conclusions: Omega 3 Fatty acid treatment inhibited $IL-1\beta$-stimulated loss of Cx43 protein, and more importantly, inhibited loss of Cx43 function by inhibiting translocation of $NF\kappa \beta$. In the intact heart a diet enriched in Omega 3 Fatty Acids limited loss of Cx43 at the intercalated disk in the heart following MI. These data suggest that one of cardio-protective mechanisms by which Omega 3 Fatty acids work includes prevention of the pro-arrhythmic loss of Cx43 post MI and the attenuation of cardiac fibrosis after injury

GP and nurses' perceptions of how after hours care for people receiving palliative care at home could be improved: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Primary health care providers play a dominant role in the provision of palliative care (PC) in Australia but many gaps in after hours service remain. In some rural areas only 19% of people receiving palliative care achieve their goal of dying at home. This study, which builds on an earlier qualitative phase of the project, investigates the gaps in care from the perspective of general practitioners (GPs) and PC nurses.</p> <p>Methods</p> <p>Questionnaires, developed from the outcomes of the earlier phase, and containing both structured and open ended questions, were distributed through Divisions of General Practice (1 urban, 1 rural, 1 mixed) to GPs (n = 524) and through a special interest group to palliative care nurses (n = 122) in both rural and urban areas.</p> <p>Results</p> <p>Questionnaires were returned by 114 GPs (22%) and 52 nurses (43%). The majority of GPs were associated with a practice which provided some after hours services but PC was not a strong focus for most. This was reflected in low levels of PC training, limited awareness of the existence of after hours triage services in their area, and of the availability of Enhanced Primary Care (EPC) Medicare items for care planning for palliative patients. However, more than half of both nurses and GPs were aware of accessible PC resources.</p> <p>Factors such as poor communication and limited availability of after hours services were identified the as most likely to impact negatively on service provision. Strategies considered most likely to improve after hours services were individual patient protocols, palliative care trained respite carers and regular multidisciplinary meetings that included the GP.</p> <p>Conclusion</p> <p>While some of the identified gaps can only be met by long term funding and policy change, educational tools for use in training programs in PC for health professionals, which focus on the utilisation of EPC Medicare items in palliative care planning, the development of advance care plans and good communication between members of multidisciplinary teams, which include the GP, may enhance after hours service provision for patients receiving palliative care at home. The role of locums in after PC is an area for further research</p

Comparative mitogenomics of the Decapoda reveals evolutionary heterogeneity in architecture and composition

The emergence of cost-effective and rapid sequencing approaches has resulted in an exponential rise in the number of mitogenomes on public databases in recent years, providing greater opportunity for undertaking large-scale comparative genomic and systematic research. Nonetheless, current datasets predominately come from small and disconnected studies on a limited number of related species, introducing sampling biases and impeding research of broad taxonomic relevance. This study contributes 21 crustacean mitogenomes from several under-represented decapod infraorders including Polychelida and Stenopodidea, which are used in combination with 225 mitogenomes available on NCBI to investigate decapod mitogenome diversity and phylogeny. An overview of mitochondrial gene orders (MGOs) reveals a high level of genomic variability within the Decapoda, with a large number of MGOs deviating from the ancestral arthropod ground pattern and unevenly distributed among infraorders. Despite the substantial morphological and ecological variation among decapods, there was limited evidence for correlations between gene rearrangement events and species ecology or lineage specific nucleotide substitution rates. Within a phylogenetic context, predicted scenarios of rearrangements show some MGOs to be informative synapomorphies for some taxonomic groups providing strong independent support for phylogenetic relationships. Additional comparisons for a range of mitogenomic features including nucleotide composition, strand asymmetry, unassigned regions and codon usage indicate several clade-specific trends that are of evolutionary and ecological interest

Statistical Fit is like Beauty: a Rasch and Factor Analysis of the Scottish PROM

Chaplains help people face some of the most complex, intractable and traumatic issues in their lives. Spiritual care works. Unfortunately, spiritual needs are rarely met in health and social care because a) spiritual distress is not recognised as such, and b) chaplain interventions are undervalued and misunderstood. The Scottish Patient Reported Outcome Measure (PROM) © was created to help provide evidence for the impact of chaplain interventions. The aim of this study was to establish whether the PROM could also be used to identify patients in need of chaplain interventions. To test this psychometrically, Rasch and Confirmatory Factor Analysis was conducted on an international dataset of post intervention PROMS from UK, Europe and Australia completed between 2018–2020 (n = 1117). The data fit the Rasch model, and the PROM demonstrated uni-dimensionality, construct validity and reliability, meaning PROM scores represent a coherent concept. Higher scores represented lower levels of spiritual distress, and the mean score was 12 out of 20. PROM score of 9 was one standard deviation below the norm, a metric routinely used to identify ‘clinically important difference’ in psychometric scales. A Scottish PROM© score of 9 and under could therefore identify people for whom chaplaincy may be beneficial. The clinical implications of this are considerable

Change in Knowledge of and Adherence to the Low-Sodium Diet in Patients with Heart Failure after Nutrition Education by a Registered Dietitian Nutritionist

Nutrition intervention by a registered dietitian nutritionist (RDN) is effective in improving patients’ knowledge or adherence to low-sodium diet (LSD, &lt;2,000 mg/d); however, changes in knowledge and adherence in heart failure (HF) patients.   have not been simultaneously assessed in the same study Therefore, the objective of the present study was to identify both HF patient sodium knowledge and adherence to the LSD before and after an education session with an RDN. A quasi-experimental study with a one-group, pre-test post-test design was conducted. An RDN conducted a 15-minute individualized nutrition education regarding the LSD at the initial visit. Sodium knowledge was measured by the Parkland Sodium Knowledge Test, and sodium intake was measured by a 29-item sodium-specific food frequency questionnaire created by NutritionQuest© at both the initial and follow-up visits. A total of 71 patients were educated on the LSD and assessed for changes in sodium knowledge and intake at their next visit. Most patients were middle aged, obese, male, and non-Hispanic Black with an education level of greater than 12 years. At the initial visit, the majority of patients were considered knowledgeable but not accordant to the LSD. Following RDN education, sodium knowledge significantly improved and sodium intake significantly decreased. RDNs should be included as members of the HF multidisciplinary team to increase sodium knowledge and reduce sodium intake through individualized nutrition education

Accurate MALDI-TOF/TOF Sequencing of One-Bead−One-Compound Peptide Libraries with Application to the Identification of Multiligand Protein Affinity Agents Using in Situ Click Chemistry Screening

Combinatorial one-bead−one-compound (OBOC) peptide libraries are widely used for affinity screening, and the sequencing of peptides from hit beads is a key step in the process. For rapid sequencing, CNBr cleavage of the peptides from the beads, followed by de novo sequencing by MALDI-TOF/TOF, is explored. We report on a semiautomated sequencing algorithm and validate it through comparison against Edman degradation sequencing. The initial 44% sequencing success rate of the standard de novo sequencing software was improved to nearly 100%. The sequencing algorithm incorporates existing knowledge of amino acid chemistry and a new strategy for differentiating isobaric amino acids. We tested the algorithm by using MALDI-TOF/TOF to identify a peptide biligand affinity agent against the protein bovine carbonic anhydrase II, starting from comprehensive one-bead−one-compound peptide libraries comprised of non-natural and artificial amino acid components and using the strategy of in situ click/OBOC library screening

Effect of Exposure of Human Monocyte-Derived Macrophages to High, versus Normal, Glucose on Subsequent Lipid Accumulation from Glycated and Acetylated Low-Density Lipoproteins

During atherosclerosis monocyte-derived macrophages accumulate cholesteryl esters from low-density lipoproteins (LDLs) via lectin-like oxidised LDL receptor-1 (LOX-1) and class AI and AII (SR-AI, SR-AII) and class B (SR-BI, CD36) scavenger receptors. Here we examined the hypothesis that hyperglycaemia may modulate receptor expression and hence lipid accumulation in macrophages. Human monocytes were matured into macrophages in 30 versus 5 mM glucose and receptor expression and lipid accumulation quantified. High glucose elevated LOX1 mRNA, but decreased SR-AI, SR-BI, LDLR, and CD36 mRNA. SR-BI and CD36 protein levels were decreased. Normo- and hyperglycaemic cells accumulated cholesteryl esters from modified LDL to a greater extent than control LDL, but total and individual cholesteryl ester accumulation was not affected by glucose levels. It is concluded that, whilst macrophage scavenger receptor mRNA and protein levels can be modulated by high glucose, these are not key factors in lipid accumulation by human macrophages under the conditions examined

Kynurenic acid as a biochemical factor underlying the association between Western-style diet and depression : a cross-sectional study

Consumption of a Western-style diet (WS-diet), high in saturated fat and added sugar, is associated with increased depression risk. However, the physiological mechanisms underlying the relationship requires elucidation. Diet can alter tryptophan metabolism along the kynurenine pathway (KP), potentially linking inflammation and depression. This study aimed to examine whether urinary inflammatory markers and KP metabolites differed according to WS-diet consumption and depression severity. Depression symptoms and habitual WS-diet consumption were assessed in 169 healthy adults aged 17–35 recruited from two experimental studies. Targeted metabolomics profiling of seven KP metabolites, ELISA-based assays of interleukin-6 (IL-6) and C-reactive protein (CRP) were performed using urine samples collected from the participants. Parametric tests were performed for group comparison and associations analysis. Multilevel mixed-effect modelling was applied to control for biases. Higher intake of WS-diet was associated with lower levels of neuroprotective kynurenic acid (KA; R = −0.17, p = 0.0236). There were no differences in IL-6 or CRP across diet groups (p > 0.05). Physical activity had negative associations with most KP metabolites. Mixed-effects regression analysis showed the glutamatergic inhibitor, KA, was the only biomarker to have a significant association with depression symptoms in a model adjusted for demographic and lifestyle variables: a unit increase in KA was associated with 0.21 unit decrease in Depression Anxiety and Stress Scale-21 depression score (p = 0.009). These findings suggest that urinary KA is associated with both habitual WS-diet intake, and levels of depression symptoms, independent of inflammation. Findings support the role of neuroprotection and glutamatergic modulation in depression. We propose that KA may act as endogenous glutamatergic inhibition in regulating depression severity in the absence of inflammation. Further comparison with blood-based markers will assist in validating the utility of non-invasive urine samples for measuring KP metabolites