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Background: Patients in receipt of palliative care services are often viewed primarily as recipients of support from their family caregiver. There is a dearth of evidence in palliative care on what comprises mutual support between patients and their family caregivers in palliative care. Aim: To identify processes of mutual support between patients and family caregivers in palliative care. Design: Qualitative study comprising semi-structured interviews. Data were analysed using grounded theory procedures. Setting/participants: Fifteen patients with advanced illness (cancer n = 14, neurodegenerative n = 1) and 21 family caregivers recruited from a large regional-based hospice. Results: Mutual support between patients and family caregivers comprised two primary modes in which support was provided and received. Mutual support involved both patients and family caregivers providing similar types of support to each other, and which typically manifested as emotional support. However, mutual support also occurred when patients reciprocated by providing emotional support to their family caregivers to compensate for other forms of support which they felt no longer able to provide. Patients supported family caregivers by involving them in decision-making for care and both patient and family caregiver preferences were influenced by obligation to their respective other. Mutual support comprised both disclosure and concealment. Involving family caregivers in patient care decision-making was intended by patients to help family caregivers adjust to a caregiving role. Conclusions: The findings inform the development and delivery of psychosocial interventions for patients and family caregivers in palliative care aimed at facilitating supportive relations between them. [ABSTRACT FROM AUTHOR]

Patients and informal caregivers in palliative care can reciprocate in supporting one another. However, how reciprocal support among patients and informal caregivers in palliative care impacts on their decision making for care is not well understood. To identify how reciprocal support among patients with advanced illness and their informal caregivers in specialist palliative care impacts on their decision making for care. Between July 2021 and May 2022, 30 qualitative interviews were conducted with 14 patient and caregiver dyads, seven nondyad caregiver participants and one nondyad patient participant (total n = 36), recruited from a large regional specialist palliative care service. Data were analyzed using Corbin and Strauss grounded theory method. Reciprocal support among patients and informal caregivers was underpinned by obligation and choice. Caregivers who felt obliged to care had difficulty communicating with the patient about the patient's preferences for care and their own wishes for patient care. Patients who felt obliged to accept support from their caregiver tended to minimize caregiver participation in decision making which made caregivers feel disempowered in discussions about patient care. Caregivers tended to be more involved in decision making when caregivers assumed caregiving duties by choice and when the patient did not feel restricted by their reliance on their caregiver. Open communication between patients and caregivers made patients more trusting of their caregiver. Patient and caregiver dyadic interventions in specialist palliative care involving decision making need to account for how obligation and choice manifest and function between the patient and caregiver. [ABSTRACT FROM AUTHOR]

Systemic inflammation is commonly reported in depression, with dysregulation of both the innate and adaptive arms of the immune system documented. Obtaining ratios of neutrophils, platelets, and monocytes to counts of lymphocytes (NLR, PLR, MLR, respectively) represents a low-cost and easily reproducible measure of an individual's inflammatory burden that can be calculated effortlessly from routine clinical full white blood cell counts. Electroconvulsive therapy (ECT) remains the most effective acute antidepressant treatment for depression but is often limited by its cognitive side-effects. Here, we examined differences in blood cell ratios in subgroups of depressed patients (unipolar/bipolar, psychotic/non-psychotic, early-onset/late-onset) and ECT-related subgroups (responder/non-responder, remitter/non-remitter). We also explored the relationships between blood cell ratios and depression severity and immediate cognitive outcomes post-ECT. Our results show baseline NLR was raised in patients with psychotic depression. In the entire group of patients, significant negative correlations were noted between the PLR and SII and baseline HAM-D24 score, signifying that lower systemic inflammation is associated with more severe depressive symptoms. Significant positive correlations were noted between various blood cell ratios and mean time to recovery of orientation in the entire group of patients and in depression subgroups, indicating that increased peripheral inflammation is linked to worse cognitive outcomes post-ECT. Overall, our results suggest that assessment of blood cell ratios could be useful for predicting mood changes in patients at risk of developing depressive episodes or relapse following successful treatment or for identifying those at risk for cognitive side-effects following ECT. [ABSTRACT FROM AUTHOR]

The Visual Research Abstract (VRA) was initially conceived as a pedagogical strategy to assist undergraduate students to navigate and understand the structure of their dissertation and the theoretical activities relating to fashion research at its earliest stages. The paper is guided by action research and collects data using a structured online questionnaire across the third-year (L. 6) and second-year (L. 5) fashion students at a UK Arts University and is aimed to evaluate and refine the pedagogical method. The research explores the student experience regarding their application of the tool, and the proposed strategies for refinement. The findings reveal that the VRA is a useful pedagogical strategy in fashion education to navigate the theoretical structure of the written dissertation closely aligned to a student's final major project. Consequently, this approach has been discussed in the paper and adopted by several subject disciplines within the Arts University environment. [ABSTRACT FROM AUTHOR]

Recent discoveries by Solon-Biet and colleagues highlight the importance of nutritional context for addressing current controversies in Fibroblast Growth Factor 21 (FGF21) biology. Through a series of complex studies, the authors explored the physiological and pharmacological effects of FGF21 on feeding behavior and energy balance under differing nutritional and metabolic statuses. [ABSTRACT FROM AUTHOR]

Telomerase, the DNA polymerase responsible for maintaining telomere length, has previously been implicated in depression and the response to antidepressant drugs. In this study, we aimed to compare telomerase activity in peripheral blood mononuclear cells between patients with severe depression recruited as part of the KEEP-WELL Trial (Ketamine for Depression Relapse Prevention Following ECT; NCT02414932) and age- and sex-matched healthy volunteers both at baseline/pre-ECT and at follow-up 1 month later for controls or in patients after a course of ECT. We found no differences in telomerase activity between patients with depression (n = 20) compared to healthy controls (n = 33) at baseline/pre-ECT, or between patients treated with ECT compared to controls at follow-up. In patients, telomerase activity was not associated with mood, as assessed by the 24-item Hamilton Rating Scale for Depression, or the duration of the current depressive episode. Additionally, we found no significant relationship between telomerase activity and exposure to recent or childhood adversity in either the patient or control groups. Overall, our results suggest that telomerase activity is not associated with depression, the therapeutic response to ECT, or exposure to adversity. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore an integrated graduate internship programme (IGIP), developing specialist skills in digital fashion at a UK creative arts university. Using a case study approach, the data were collected through semi-structured interviews and online questionnaires from graduates who had previously completed a one-year IGIP from 2015 to 2019. It investigates how the programme impacted a graduate's future studies and employment transitions and whether the support of this unique programme provided an experiential and transformative approach than merely a pathway to postgraduate careers or studies. Future research could incorporate a longitudinal study across a wider number of subject specialisms/courses in the Higher Education sector. Implications for educators and industry professionals are notable. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is the most acutely effective treatment for severe treatment-resistant depression. However, there are concerns about its cognitive side-effects and we cannot yet confidently predict who will experience these. Telomeres are DNA-protein complexes that maintain genomic integrity. In somatic cells, telomeres shorten with each cell division. Telomere length (TL) can thus provide a measure of 'biological' aging. TL appears to be reduced in depression, though results are mixed. We sought to test the following hypotheses: (1) that TL would be shorter in patients with depression compared to controls; (2) that TL would be a predictor of response to ECT; and (3) that shorter TL would predict cognitive side-effects following ECT. Method: We assessed TL in whole blood DNA collected from severely depressed patients (n = 100) recruited as part of the EFFECT-Dep Trial and healthy controls (n = 80) using quantitative real-time polymerase chain reaction. Mood and selected cognitive measures, including global cognition, re-orientation time, and autobiographical memory, were obtained pre-/post-ECT and from controls. Results: Our results indicate that TL does not differ between patients with depression compared to controls. TL itself was not associated with mood ratings and did not predict the therapeutic response to ECT. Furthermore, shorter baseline TL is not a predictor of cognitive side-effects post-ECT. Conclusions: Overall, TL assessed by PCR does not represent a useful biomarker for predicting the therapeutic outcomes or risk for selected cognitive deficits following ECT. [ABSTRACT FROM AUTHOR]

Background: Ketamine is a rapid-acting antidepressant but its mechanism remains unclear. Vascular endothelial growth factor growth factor (VEGF) has been reported in the antidepressant action of ketamine in rodents. VEGF and pigment epithelial-derived factor (PEDF) signalling are closely linked and both are dysregulated in depression. We explored the effect of a single infusion of ketamine, with midazolam as comparison, on peripheral whole blood mRNA levels of vascular endothelial growth factor A (VEGFA) and PEDF, and the VEGFA/PEDF ratio, in patients with depression.Methods: Twenty-five patients with depression were randomised to either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) infusions over 40 min. Blood plasma samples were taken 1 h before the first infusion and 4 h after the infusion start. mRNA was extracted and qRT-PCR performed to analyse gene expression.Results: Single infusions of ketamine and midazolam both decreased depression scores (F(1,21) = 102.40, p < 0.000). There was a significant group × time interaction for VEGFA mRNA levels (F(1, 21) = 5.207, p = 0.029), with ketamine increasing VEGFA levels. There was no significant effect of either ketamine or midazolam on PEDF levels. There was a significant group × time interaction for VEGFA/PEDF mRNA ratio, with ketamine alone increasing this ratio (F(1, 11) = 12.085, p = 0.005).Limitations: Patients were on psychotropic medication and continued treatment as usual throughout the study.Conclusions: These preliminary results support a role for VEGF in the action of ketamine and suggest a novel role for VEGF/PEDF in the molecular response to ketamine. [ABSTRACT FROM AUTHOR]

• Kynurenine metabolite concentrations were lower in depressed patients compared to controls. • Kynurenine metabolite concentrations correlate with improvement in mood score. • Metabolites associate with treatment response in unipolar depressed patients. • Pathway metabolites may differentiate ECT remitters from those who relapse. Tryptophan and kynurenine pathway (KP) metabolites are implicated in the pathophysiology of depression. We aimed to investigate their plasma concentrations in medicated patients with depression (n = 94) compared to age- and sex-matched healthy controls (n = 57), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting, taking account of co-variables including ECT modality and heterogenous psychopathology. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D24). Tryptophan (TRP) and kynurenine (KYN) metabolite concentrations [anthranilic acid (AA), 3-hydroxyanthranilic acid (3HAA), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA)] and KYNA/KYN and KYNA/quinolinic acid (QUIN) ratios were lower in patients compared to controls. For the total group there was no significant change in KP metabolites post-ECT or correlations with mood ratings. However, improvements in mood score were correlated with increased KYN, 3-hydroxykynurenine (3HK), 3HAA, QUIN, and KYN/TRP in a subgroup of unipolar depressed patients. Additionally, in remitters baseline KYN, 3HK, and QUIN were associated with baseline HAM-D24 scores, and changes in 3HK and 3HAA concentrations post-ECT correlated with improvement in mood. KYN, KYNA, AA, 3HK, XA, PA, and QUIN were increased in a smaller 3-month follow-up group (n = 19) compared to pre-ECT concentrations. Overall, the results indicate that ECT mobilizes the KP, where a moderate association between selected metabolites and treatment response in unipolar depressed patients is evident. [ABSTRACT FROM AUTHOR]

Background: The transcriptional coactivator peroxisome proliferator-activated receptor- γ coactivator (PGC-1 α), termed the 'master regulator of mitochondrial biogenesis', has been implicated in stress and resilience to stress-induced depressive-like behaviours in animal models. However, there has been no study conducted to date to examine PGC-1 α levels in patients with depression or in response to antidepressant treatment. Our aim was to assess PGC-1α mRNA levels in blood from healthy controls and patients with depression pre-/post-electroconvulsive therapy (ECT), and to examine the relationship between blood PGC-1α mRNA levels and clinical symptoms and outcomes with ECT. Methods: Whole blood PGC-1α mRNA levels were analysed in samples from 67 patients with a major depressive episode and 70 healthy controls, and in patient samples following a course of ECT using quantitative real-time polymerase chain reaction (qRT-PCR). Exploratory subgroup correlational analyses were carried out to determine the relationship between PGC-1α and mood scores. Results: PGC-1α levels were lower in patients with depression compared with healthy controls (p = 0.03). This lower level was predominantly accounted for by patients with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1α levels in the depressed group as a whole, though exploratory analyses revealed a significant increase in PGC-1α in patients with psychotic unipolar depression post-ECT (p = 0.045). We found no relationship between PGC-1α mRNA levels and depression severity or the clinical response to ECT. Conclusions: PGC-1 α may represent a novel therapeutic target for the treatment of depression, and be a common link between various pathophysiological processes implicated in depression. [ABSTRACT FROM AUTHOR]

Abstract The E2F transcription factors are a group of proteins that bind to the promotor region of the adenovirus E2 gene. E2F1, the first family member to be cloned, is linked to functions including cell proliferation and apoptosis, DNA repair, cell senescence and metabolism. We recently performed a deep sequencing study of micro-RNA changes in whole blood following ECT. Two micro-RNAs (miR-126-3p and miR-106a-5p) were identified and gene targeting analysis identified E2F1 as a shared target of these miRNAs. To our knowledge, no studies have examined E2F1 mRNA levels in patients with depression. Peripheral blood E2F1 mRNA levels were therefore examined in patients with depression, compared to healthy controls, and the effects of a course of ECT on peripheral blood E2F1 mRNA was investigated. Depressed patient and healthy control groups were balanced on the basis of age and sex. E2F1 mRNA levels were significantly lower in depressed patients in comparison to controls (p =.009) but did not change with ECT. There was no relationship between baseline E2F1 levels and depression severity, response to treatment, presence of psychosis or polarity of depression. There were no significant correlations between E2F1 levels and mood scores based on the HAM-D24. These results indicate that reduced peripheral blood E2F1 mRNA could be a trait feature of depression. Highlights • Peripheral blood E2F1 mRNA levels are significantly lower in patients with depression than in healthy controls. • Peripheral blood E2F1 mRNA levels do not change following a course of ECT. • Peripheral blood E2F1 mRNA levels are not related to depression severity and are not associated with the response to ECT. [ABSTRACT FROM AUTHOR]

Highlights • GILZ is a downstream mediator of glucocorticoids. • GILZ mRNA levels are low in patients with depression versus controls. • GILZ mRNA levels are further reduced by ECT. • GILZ may play a role in antidepressant mechanism. Abstract Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA)-axis is commonly observed in patients with depression. The delayed feedback system that mediates inhibition of HPA-axis activation is regulated by glucocorticoid receptors (GRs) found in stress-responsive areas of the brain. Glucocorticoid-induced leucine zipper (GILZ) is a key molecule in glucocorticoid biology and is thought to mediate the downstream anti-inflammatory effects of GRs. Previous reports suggest that GILZ levels are altered in the blood and brains of patients with, and animal models of, depression. However, no study has yet investigated the effects of antidepressant treatment on GILZ. Therefore, our aim was to examine peripheral blood GILZ mRNA levels in patients with depression (n = 88) compared to age- and sex-matched healthy controls (n = 63), and in patients with depression following treatment with a course of electroconvulsive therapy (ECT). We also assessed the relationship between GILZ and mood and clinical outcomes following ECT. GILZ mRNA levels were assessed using qRT-PCR. GILZ levels were found to be significantly lower in patients with depression compared to controls (p < 0.002), and ECT further decreased GILZ levels (p = 0.05). Both of these results survived adjustment for potential covariates. However, we found no association between GILZ and mood scores. Overall, these results suggest that GILZ is involved in the pathophysiology of depression and the peripheral molecular response to ECT. [ABSTRACT FROM AUTHOR]

Both animal and human studies have implicated the neurotrophic and angiogenic mediator vascular endothelial growth factor (VEGF) in depression, with meta-analyses, indicating that protein levels are raised in patients with depression. In line with this, we have previously shown that VEGFA mRNA levels are higher in whole blood from patients with depression compared to controls, in particular in patients with psychotic unipolar depression, and that treatment with electroconvulsive therapy (ECT) alters VEGFA mRNA levels. The aim of the present study was, therefore, to extend this previous work by assessing plasma VEGF protein levels in patients with depression compared to healthy controls, and in patients following treatment with ECT. We found that there was no difference between controls and patients with depression with regard to plasma VEGF (p = 0.59), and that VEGF levels were unaltered by ECT (p = 0.09) after correction for potential covariates. We found no correlation between VEGF protein and mRNA levels. Within the subgroup of patients receiving treatment with bitemporal ECT (n = 34), we identified a moderate negative correlation (ρ = − 0.54, p = 0.001) between the change in VEGF and the change in depression severity following treatment; however, no other association between VEGF and mood, responder/remitter status, polarity of depression, or presence of psychosis were found. Overall, our results indicate that the measurement of VEGF protein is not a useful marker for depression or response to treatment, and suggest that the measurement of VEGFA mRNA may prove more useful. [ABSTRACT FROM AUTHOR]

Abstract Sirtuins are a family of nicotinamide adenine dinucleotide (NAD+) dependent enzymes that regulate cellular functions through deacetylation of protein targets. They have roles in both the periphery and central nervous system and have been implicated in depression biology. A recent genome-wide association study has identified a locus for major depression in the Sirtuin1 gene (SIRT1) and lower blood levels of SIRT1 mRNA in patients with depression have also been observed in two studies. To our knowledge, no studies have examined the effect of treatment on SIRT1 levels in patients with depression. We therefore examined SIRT1 mRNA levels in a well characterised group of patients with depression, compared to healthy controls, and characterised the effects of a course of electroconvulsive therapy (ECT) on peripheral blood SIRT1 mRNA. Depressed patients (n = 91) were matched to healthy controls (n = 85) on the basis of age and sex. In line with previous studies, blood SIRT1 mRNA levels were lower in depressed patients in comparison to controls (p = 0.005). However, ECT had no effect on SIRT1 levels (p = 0.67). There was no relationship between baseline pre-ECT SIRT1 levels and depression severity, change in mood scores, suicidality, depression polarity, presence of psychosis, or response to treatment. There was a trend for a negative association between an increase in SIRT1 mRNA and a decrease in HAM-D24 scores in ECT responders and remitters. These results indicate that reduced peripheral blood SIRT1 mRNA could be a trait feature of depression. [ABSTRACT FROM AUTHOR]

The objective of this study was to gain basic knowledge of breast cancer survivors’ satisfaction with wearable products designed specifically for their needs. To achieve this objective a questionnaire was administered using a seven-point Likert scale and open-ended questions to query information regarding participants’ cancer diagnoses, experiences, and satisfaction with prostheses, bras, and lymphedema sleeves. The 51 participants represented the full range of cancer stages from treated pre-cancers to metastatic cancer. Participants had experienced various types of treatment including lumpectomy, mastectomy, lymph node dissection, radiation therapy, and reconstruction surgery. Participants described side effects of cancer treatment that influenced their satisfaction with wearable products and also provided opinions concerning design of the products. Participants were moderately satisfied with prostheses, mastectomy bras, and lymphedema sleeves, indicating that designers have the opportunity to work with breast cancer survivors to redesign and improve the products. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction may play a role in various psychiatric conditions. Mitochondrial DNA copy number (mtDNAcn), the ratio of mitochondrial DNA to nuclear DNA, represents an attractive marker of mitochondrial health that is easily measured from stored DNA samples, and has been shown to be altered in depression. In this study, we measured mtDNAcn in whole blood samples from medicated patients with depression (n = 100) compared to healthy controls (n = 89) and determined the relationship between mtDNAcn and depression severity and the therapeutic response to electroconvulsive therapy (ECT). We also explored the relationship between mtDNAcn and telomere length and inflammatory markers. Our results show that mtDNAcn was significantly elevated in blood from patients with depression when compared to control samples, and this result survived statistical adjustment for potential confounders (p = 0.002). mtDNAcn was significantly elevated in blood from subgroups of patients with non-psychotic or unipolar depression. There was no difference in mtDNAcn noted in subgroups of ECT remitters/non-remitters or responders/non-responders. Moreover, mtDNAcn was not associated with depression severity, telomere length, or circulating inflammatory marker concentrations. Overall, our results show that mtDNAcn is elevated in blood from patients with depression, though whether this translates to mitochondrial function is unknown. Further work is required to clarify the contribution of mitochondria and mtDNA to the pathophysiology of depression and the therapeutic response to antidepressant treatments. • mtDNAcn represents an attractive marker of measuring mitochondrial health. • mtDNAcn was elevated in whole blood from depressed patients versus controls. • mtDNAcn was not related to depression severity or clinical outcomes following ECT. • mtDNAcn was not associated with telomere length or circulating inflammatory markers. [ABSTRACT FROM AUTHOR]

The long-acting, highly lipophilic, β 2 -adrenoceptor agonist clenbuterol may represent a suitable therapeutic agent for the treatment of neuroinflammation as it drives an anti-inflammatory response within the CNS. However, clenbuterol is also known to increase the expression of IL-1β in the brain, a potent neuromodulator that plays a role in provoking sickness related symptoms including anxiety and depression-related behaviours. Here we demonstrate that, compared to the immunological stimulus lipopolysaccharide (LPS, 250 μg/kg), clenbuterol (0.5 mg/kg) selectively up-regulates expression of the central IL-1 system resulting in a mild stress-like response which is accompanied by a reduction in locomotor activity and food consumption in rats. We provide further evidence that clenbuterol-induced activation of the central IL-1 system occurs in a controlled and selective manner in tandem with its negative regulators IL-1ra and IL-1RII. Furthermore, we demonstrate that peripheral β 2 -adrenoceptors mediate the suppression of locomotor activity and food consumption induced by clenbuterol and that these effects are not linked to the central induction of IL-1β. Moreover, despite increasing central IL-1β expression, chronic administration of clenbuterol (0.03 mg/kg; twice daily for 21 days) fails to induce anxiety or depressive-like behaviour in rats in contrast to reports of the ability of exogenously administered IL-1 to induce these symptoms in rodents. Overall, our findings suggest that clenbuterol or other selective β 2 -adrenoceptor agonists could have the potential to combat neuroinflammatory or neurodegenerative disorders without inducing unwanted symptoms of depression and anxiety. [ABSTRACT FROM AUTHOR]

• CRP, IL-6, IL-10, and TNF-α were higher in depressed patients than in controls. • ECT did not alter inflammatory mediator concentrations. • We found no relationship between inflammatory mediators and mood or cognition. The inflammatory response may play a role in depression and the response to antidepressants. Electroconvulsive therapy (ECT), the most acutely powerful antidepressant treatment, can also affect the innate immune system. Here, we determined circulating blood concentrations of the inflammatory mediators C-reactive protein (CRP), IL-1β, IL-6, IL-10, and TNF-α in depressed patients compared to healthy controls and assessed the effect of ECT on their concentrations. Relationships between inflammatory mediator concentrations and mood/cognition scores were also explored. Plasma CRP, IL-1β, IL-6, IL-10, and TNF-α concentrations were examined in 86 depressed patients and 57 controls. Relationships between inflammatory mediators and clinical or cognitive outcomes following ECT were assessed using correlation and linear regression analyzes, respectively. CRP, IL-6, IL-10, and TNF-α were elevated in patients at baseline/pre-ECT compared to controls. However, only IL-6 and TNF-α survived adjustment for potential confounders. IL-1β was undetectable in most samples. ECT did not significantly alter plasma concentrations of any of the inflammatory mediators. No relationship was identified between CRP, IL-6, IL-10, and TNF-α and mood or neurocognitive scores. Overall, our data do not support a major role for these four inflammatory markers in clinical outcomes following ECT or in cognition. [ABSTRACT FROM AUTHOR]

Globally, cancer incidence and mortality are increasing, and most of the burden is shifting to low- and middle-income countries (LMICs), where patients often present with late-stage disease and severe pain. Unfortunately, LMICs also face a disproportionate lack of access to pain-relieving medicines such as morphine, despite the medical and scientific literature that shows morphine to be effective to treat moderate and severe cancer pain. In 2008, an oncologist from Nepal, one of the poorest countries in the world, was selected to participate in the International Pain Policy Fellowship, a program to assist LMICs, to improve patient access to pain medicines. Following the World Health Organization public health model for development of pain relief and palliative care, the Fellow, working with colleagues and mentors, has achieved initial successes: three forms of oral morphine (syrup, immediate-release tablets, and sustained-release tablets) are now manufactured in the country; health-care practitioners are receiving training in the use of opioids for pain relief; and a new national palliative care association has developed a palliative care training curriculum. However, long-term implementation efforts, funding, and technical assistance by governments, philanthropic organizations, and international partners are necessary to ensure that pain relief and palliative care become accessible by all in need in Nepal and other LMICs. [ABSTRACT FROM AUTHOR]

Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery. [ABSTRACT FROM AUTHOR]

Summary: The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated in hypothalamic–pituitary–adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were placed into 3 groups (n =15/group) according to genotype [wild-type (WT); heterozygous mutant (HET); and homozygous mutant (HOM)]. Basal (pre-stress) plasma adrenocorticotropic hormone (ACTH) and corticosterone were measured in the AM and PM, and the HPA axis response to restraint was assessed in the AM. Rats were perfused at 2h after restraint to assess the effect of loss of MC4R on stress-induced c-Fos immunolabeling in stress-regulatory brain regions. We find that basal (non-stress) AM and PM plasma ACTH and corticosterone showed a normal diurnal rhythm that was not altered according to genotype. Consistent with this, adrenal and thymus weights were unaffected by genotype. However, the plasma ACTH and corticosterone responses to restraint were significantly reduced by loss of MC4R function. Likewise, stress-induced c-Fos immunolabeling in both PVH and MeA was significantly reduced by loss of Mc4r function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic and stress systems. [ABSTRACT FROM AUTHOR]

Highlights: [•] Alterations in miRNAs may be informative about the mechanism of action of ECS/ECT. [•] We examined levels of selected BDNF-associated miRNAs in rat brain and blood following ECS. [•] miR-212 was significantly increased in dentate gyrus after acute and chronic ECS. [•] miR-212 levels in dentate gyrus positively correlated with levels in whole blood. [•] miRNAs may pose suitable biomarkers to predict the response to ECT. [Copyright &y& Elsevier]

Abstract: Complex interactions link psychological stress and aging - stress generally promotes aging processes, and conversely, aging can contribute to stress dysregulation. Stress and aging have remarkably similar effects on brain. Both induce neuroinflammation and alter neuronal metabolism and activity, which to varying extents are causally-linked to the development of stress and aging pathology. As such, induction of one or more of these brain disturbances by either stress or aging could predispose for the development of dysfunction in the other. Notably, peroxisome proliferator-activated receptor γ (PPARγ) is expressed in brain regions that regulate both stress and aging (e.g., hippocampus) and can act to prevent the consequences of aging and stress on the brain. In addition, PPARγ agonists reduce the physiological stress response itself. Thus, PPARγ may represent a critical mechanistic link between brain aging and stress that could hold therapeutic potential for the prevention and treatment of age-related cognitive and mood disorders. [Copyright &y& Elsevier]

The skeletal remains of an adult Sadlermiut Inuit woman were excavated from a grave at the Native Point site on Southampton Island, Nunavut, Canada, in 1959. Forming part of the woman's mortuary assemblage was a small wooden human figurine that had been perforated in its face, chest, and pelvic regions. Such modifications had not previously been noted on Thule Inuit anthropomorphic carvings and the rationale for their presence on this figurine was not initially apparent. However, examination of the associated human remains revealed skeletal abnormalities that matched two of the figurine's three perforations; indirect evidence suggests a third now archaeologically invisible soft tissue pathology was also present. This paper uses ethnohistoric accounts of the Sadlermiut, in combination with ethnographic observations made among other Inuit groups, to suggest that the Native Point figurine was not simply a "doll," but was instead an aarnguaq (object with powers) wielded by a shaman as part of a healing ritual intended to heal an obviously ill person. [ABSTRACT FROM AUTHOR]

Accessible summary [ABSTRACT FROM AUTHOR]

Abstract: In recent papers, Coltrain et al. (Sealing, whaling and caribou: the skeletal isotope chemistry of eastern Arctic foragers, Journal of Archaeological Science 31, 39–57) and Coltrain (Sealing, whaling and caribou revisited: additional insights from the skeletal isotope chemistry of eastern Arctic foragers, Journal of Archaeological Science 36, 764–775) propose that four previously excavated human skeletons from Native Point, Southampton Island, Nunavut, Canada, are Dorset Paleoeskimo and European. The suggested reclassification of one burial as Dorset is based upon a single radiocarbon assay and interpretation of isotopic values. The authors’ conclusion that three other individuals, found together inside an aboriginal dwelling, were European rests on an isotopic signature indicative of a terrestrial diet, as well as radiocarbon date ranges. This paper assesses the information used by and to reach these conclusions and, in contrast to those authors, determines that the data is equivocal at best and does not support revision of the individuals’ biocultural affinity. The paper stresses the necessarily critical role that must be given to archaeological context in any interpretation, or reinterpretation, of human remains. [Copyright &y& Elsevier]

The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPAR-γ is the target of the thiazolidinedione (TZD) class of insulin-sensitizing drugs, which have been widely prescribed to treat type 2 diabetes mellitus. A common side effect of treatment with TZDs is weight gain. Here we report a previously unknown role for central nervous system (CNS) PPAR-γ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPAR-γ, by either TZDs or hypothalamic overexpression of a fusion protein consisting of PPAR-γ and the viral transcriptional activator VP16 (VP16-PPAR-γ), led to positive energy balance in rats. Blocking the endogenous activation of CNS PPAR-γ with pharmacological antagonists or reducing its expression with shRNA led to negative energy balance, restored leptin sensitivity in high-fat-diet (HFD)-fed rats and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity. [ABSTRACT FROM AUTHOR]

Little is known of paid carers' perspectives when caring for people with intellectual disabilities at the end-of-life. Sixty four individuals from intellectual disability services took part in 12 focus groups. Interviews were analysed using framework analysis. Participants wanted to provide palliative care and felt the experience enriched practice. However, they were inadequately prepared to meet need and this often led to staff stress. A number of issues appeared to heighten stress: situations when end-of-life care decision making was challenging, when staff felt 'pushed out' by relatives and when staff did not have sufficient support or time to provide care or mourn the loss of service users. The study describes issues which contribute to the development of staff stress when providing palliative care and draws attention to areas where strategies should be developed in order to improve the quality of care provided to people with intellectual disabilities. [ABSTRACT FROM AUTHOR]

Research suggests that shortcomings exist in the provision of palliative care to people with intellectual disabilities. This mixed-methods study aimed to describe the experience, confidence and attitudes of staff to the provision of palliative care to people with intellectual disabilities. The sample was drawn from the population of one Health Service Executive area in Ireland. Staff from intellectual disability and palliative care services completed surveys and participated in focus group discussions. Three hundred and eighty-nine questionnaires were distributed and 16 focus groups were held. Fiftynine per cent of palliative care staff and 67% of intellectual disability services staff had cared for someone with intellectual disability who had died but level of experience was low. Both palliative care and intellectual disability services staff lacked confidence in their ability to provide palliative care. Staff were challenged by perceived 'differences' and 'difficulties' in the provision of care. They endorsed a partnership approach to care but focus group discussions revealed that a shared desire to cooperate was insufficient to guarantee effective collaboration. [ABSTRACT FROM AUTHOR]

Symptomatic venous thromboembolism (VTE) occurs in 15% of patients with advanced malignancy. Primary thromboprophylaxis using low-molecular-weight heparin (LMWH) is supported by Level 1A evidence but is under-utilized in the palliative setting. A systematic search was performed of Medline, Cochrane Library, EMBASE, AMED, and Web of Science for papers published between 1960 and January 2010 using search terms: 'palliative', 'thromboprophylaxis', 'thromboembolism', 'heparin', and 'advanced cancer'. Forty-two citations were obtained, of which 34 were excluded as they dealt with treatment of VTE, novel anticoagulants, or LMWH as a cancer treatment. Eight original articles were reviewed independently by two authors. Data was extracted according to a predetermined questionnaire. Studies examined practice in specialist palliative care (SPC) units, and attitudes held by a total of 32 physicians and 198 patients. Patients find LMWH acceptable, particularly patients who experienced a sudden decline in performance status. Reluctance to prescribe LMWH is based on physicians' concerns regarding negative impact on quality of life, and lack of evidence specific to the palliative care setting. In conclusion, LMWH prophylaxis should be implemented in patients with a previously good performance status who have a transiently increased risk of VTE and no contraindications. Further research is required using outcome measures specific to palliative care. [ABSTRACT FROM AUTHOR]

Abstract: Evidence indicates that the monoamine neurotransmitter noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and consequently may play a neuroprotective role where inflammatory events contribute to CNS pathology. Here we examined the ability of pharmacologically enhancing central noradrenergic tone to induce expression of anti-inflammatory cytokines in rat brain. Administration of the noradrenaline reuptake inhibitor reboxetine (15mg/kg; ip) combined with the α2-adrenoceptor antagonist idazoxan (1mg/kg; ip) induced interleukin-10 (IL-10) expression in rat cortex and hippocampus. In addition, these drug treatments induced IL-10 signaling as indicated by increased STAT3 phosphorylation and suppressor of cytokine signaling-3 (SOCS-3) mRNA expression. In contrast to the profound increase in IL-10 induced by the reboxetine/idazoxan combination, the other two broad spectrum anti-inflammatory cytokines IL-4 and TGF-β were not induced by this treatment. The ability of combined treatment with reboxetine and idazoxan to induce IL-10 and SOCS3 expression was mediated by β-adrenoceptor activation, as their induction was blocked by pre-treatment with the β-adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant β2-adrenoceptor agonist clenbuterol induced a time- and dose-dependent increase in central IL-10 and SOCS3 expression, and the ability of clenbuterol to induce IL-10 and SOCS-3 expression was blocked by the centrally acting β-adrenoceptor antagonist, propranolol, and was mimicked by the highly selective β2-adrenoceptor agonist formoterol. In all, these data indicate that increasing central noradrenergic tone induces IL-10 production and signaling in the CNS, which may protect against neurodegeneration. [Copyright &y& Elsevier]

Abstract: Evidence suggests that noradrenaline has a tonic anti-inflammatory action in the central nervous system (CNS) via its ability to inhibit expression of inflammatory mediators from glial cells. Consequently it is suggested that noradrenaline may play an endogenous neuroprotective role in CNS disorders where inflammatory events contribute to pathology. Infiltration of peripheral immune cells into the brain is driven by increased chemokine and cell adhesion molecule (CAM) expression, and is known to exacerbate neuroinflammation and thereby contribute to the disease process in a number of neurodegenerative disease states. Here we demonstrate that treatment of rats with the noradrenaline reuptake inhibitors (NRIs) desipramine and atomoxetine, agents that increase extracellular noradrenaline in the CNS, suppressed chemokine and cell adhesion molecule (CAM) expression in rat brain following a systemic challenge with bacterial lipopolysaccharide (LPS). Specifically, these agents reduced expression of the chemokines, interferon-inducible protein-10 (IP-10, CXCL-10) and regulated upon activation normal T-cell expressed and secreted (RANTES, CCL-5), and the CAMs, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule (ICAM-1) in cortex and hippocampus. The inhibitory action of NRIs on chemokines and CAM expression was mimicked by in vitro exposure of cultured glial cells to noradrenaline, but not to the NRIs themselves. These data indicate that the suppressive action of NRIs on chemokine and CAM expression that occurs in vivo is due to increased noradrenaline availability at glial cells, as opposed to a direct action of the drugs on glial cells per se. These results support the theory that noradrenaline has anti-inflammatory properties, and agents that increase noradrenaline availability in vivo can play a role in combating brain inflammation by reducing expression of chemokines and CAMs; molecules that facilitate leucocyte influx into the CNS. [Copyright &y& Elsevier]

Abstract: The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a key role in initiating an immune response within the central nervous system (CNS), and is thought to be a significant contributor to the neurodegenerative process. The actions of IL-1β can be regulated by interleukin-1 receptor antagonist (IL-1ra), which prevents IL-1β from acting on the IL-1 type I receptor (IL-1RI). Another negative regulator of the IL-1 system is the IL-1 type II receptor (IL-1RII); a decoy receptor that serves to sequester IL-1. Consequently, pharmacological strategies that tip the balance in favour of IL-1ra and IL-1RII may be of therapeutic benefit. Evidence suggests that the neurotransmitter noradrenaline elicits anti-inflammatory actions in the CNS, and consequently may play an endogenous neuroprotective role. Here we report that noradrenaline induces production of IL-1ra and IL-1RII from primary rat mixed glial cells. In contrast, noradrenaline did not alter IL-1β expression, or expression of IL-1RI or the IL-1 type I receptor accessory protein (IL-1RAcp); both of which are required for IL-1 signalling. Our results demonstrate that the ability of noradrenaline to induce IL-1ra and IL-1RII is mediated via β-adrenoceptor activation and downstream activation of protein kinase A and extracellular signal-regulated kinase (ERK). In parallel with its ability to increase IL-1ra and IL-1RII, noradrenaline prevented neurotoxicity in cortical primary neurons induced by conditioned medium from IL-1β treated mixed glial cells. These data indicate that noradrenaline negatively regulates IL-1 system in glial cells and has neuroprotective properties in situations where IL-1 contributes to pathology. [Copyright &y& Elsevier]

Abstract: Delirium is underrecognized clinically. Many tools have been developed to assist with the diagnosis of delirium, and they vary greatly in purpose, quality, and administration time. It is suggested that future development of delirium assessment instruments be guided by a dichotomization of raters into expert and nonexpert groups. Careful consideration of the needs of the two groups suggests that assessment instruments designed for nonexperts should be entirely objective, whereas those instruments developed for experts should include the full range of constructs associated with the syndrome. This conceptualization is explored in detail, and existing assessment instruments are considered briefly in light of this position. [Copyright &y& Elsevier]

Abstract: The pain and palliative care fields are encouraged to learn about government drug control policy and to engage with their governments to examine these policies and their implementation in order to address impediments to patient access to pain management. Although pain management is a necessary part of palliative care, it is often impossible because strict national and state regulations block access to opioid analgesics. It is important for us to know that in adhering to international drug treaties, governments often concentrate on drug control to the exclusion of their obligation to ensure opioid availability for medical and scientific purposes. Indeed, international health and regulatory authorities are increasingly concerned about wide disparities in national consumption of opioid analgesics and have called on governments to address barriers in their national laws and regulations that govern the prescribing of opioid analgesics. The Pain & Policy Studies Group (PPSG) has developed methods and resources to assist governments and pain and palliative care groups to examine national policies and make regulatory changes. Romania, India, and Italy are examples. The PPSG is developing several new resources, including a training program for Fellows from low- and middle-income countries, enhanced support of collaborators working on opioid availability, an internet course in international pain policy, an improved website with policy resources and country profiles, and new approaches to the study of opioid consumption indicators. [Copyright &y& Elsevier]

Summary: Unrelieved pain from cancer and HIV/AIDS is a substantial worldwide public-health problem. Inadequate pain relief is partly due to excessively strict national drug-control policies that constrain medical use of essential medicines such as morphine. Romania's drug-control policies are more than 35 years old and impose an antiquated regulatory system that is based on inpatient post-surgical management of acute pain that restricts prescription authority and makes access to opioid treatment difficult for outpatients with severe chronic pain due to cancer or HIV/AIDS. A Ministry of Health palliative-care commission used WHO guidelines to assess and recommend changes to Romania's national drug control law and regulations. The Romanian parliament has adopted a new law that will simplify prescribing requirements and allow modern pain management. Achievement of adequate pain relief is a vital part of worldwide health and will be dependent on reform of antidrug regulations in many countries. [ABSTRACT FROM AUTHOR]

People with intellectual disabilities are among the most socially excluded and vulnerable groups in Ireland today. They are at increased risk of early death and they receive poorer health care than the general population. The World Health Organization has pointed out that inequalities in service provision to this group extend to the delivery of palliative care. The population of people with intellectual disabilities is an ageing one, and its changing demographics challenge services that were originally developed for children and young adults and that focused on enabling their clients to lead full and productive lives. Conditions such as cancer, cardiovascular and respiratory disease are now leading causes of death, and this has important implications for service planning. Although the population is relatively small, its needs demand high priorities in the healthcare services. This is because many people with intellectual disabilities need support throughout their lives and have longer and more intense involvement with services than the vast majority of citizens. People with intellectual disabilities are people first, and should be recognised as individuals, rather than on the basis of definitions. However, there is reason to assess their palliative care needs as a client group. This is because people with intellectual disabilities not only have the universal palliative care needs of the general population, but also have additional and special needs. This paper reviews the palliative care needs of people with intellectual disabilities, dealing with such issues as symptomatology, communication and family dynamics. It draws attention to the gaps that currently exist in end-of-life care services for adults with intellectual disabilities and concludes that a partnership approach between the intellectual disability and palliative care services will be needed in order to provide effective patient-centred and family-oriented care. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: A study has been performed to evaluate inter-observer variability when assessing pelvic patient movement using an electronic portal imaging device (EPID). Materials and methods: Four patient image sets were used with 3–6 portal images per set. The observer group consisted of nine radiographers with 3–18 months clinical EPID experience. The observers outlined bony landmarks on a digital simulator image and used matching software to evaluate field placement errors (FPEs) on each portal image relative to the reference simulator image. Data were evaluated statistically, using a two-component analysis of variance technique, to quantify both the inter-observer variability in evaluating FPEs and inter-fraction variability in patient position relative to the residuals of the analysis. Intra-observer variability was also estimated using four of the observers carrying out three sets of repeat readings. Results: Eight sets of variance data were analysed, based on FPEs in two orthogonal directions for each of the four patient image sets studied. Initial analysis showed that both inter-observer variation and inter-fraction-patient position variation were statistically significant (P&#60;0.05) in seven of the eight cases evaluated. The averaged root-mean-square (RMS) deviation of the observers from the group mean was 1.1mm, with a maximum deviation of 5.0mm recorded for an individual observer. After additional training and re-testing of two of the observers who recorded the largest deviations from the group mean, a subsequent analysis showed the inter-observer variability for the group to be significant in only three of the eight cases, with averaged RMS deviation reduced to 0.5mm, with a maximum deviation of 2.7mm. The intra-observer variability was 0.5mm, averaged over the four observers tested. Conclusions: We have developed a quantitative approach to evaluate inter-observer variability in terms of its statistical significance compared to inter-fraction patient movement. This will assist us in training and assessing observers required to perform this task on a routine basis. [Copyright &y& Elsevier]

This study updates a previous analysis of trends in medical use and abuse of opioid analgesics, and provides data from 1997 through 2002. Two research questions were evaluated: 1) What are the trends in the medical use and abuse of frequently prescribed opioid analgesics used to treat severe pain, including fentanyl, hydromorphone, meperidine, morphine, and oxycodone? 2) What is the abuse trend for opioid analgesics as a class compared to trends in the abuse of other drug classes? Results demonstrated marked increases in medical use and abuse of four of the five studied opioid analgesics. In 2002, opioid analgesics accounted for 9.85% of all drug abuse, up from 5.75% in 1997. Increase in medical use of opioids is a general indicator of progress in providing pain relief. Increases in abuse of opioids is a growing public health problem and should be addressed by identifying the causes and sources of diversion, without interfering with legitimate medical practice and patient care. [Copyright &y& Elsevier]

Casting Stalin as the devil or Antichrist has been a productive technique in Russian literary satire. Postmodern treatments of Stalin by Victor Erofeyev, the Sots artists Komar and Melamid, and the film director Semen Aranovich have begun to reconsider the myth of Stalin's demonism and to confront the dictator's humanity.

To the extent that relatedness between mates predicts their reproductive success, individuals are expected to bias their behaviours towards opposite-sex conspecifics according to differences in kinship. Here we show that monogamous male oldfield mice, Peromyscus polionotus rhoadsi, bias their social behaviour towards unfamiliar, distantly related females according to an average 1.3% difference in their kinship to these potential mates. Males in the present study favoured less-related females. Previous empirical investigations have not demonstrated behavioural biases based on such small kinship differences. Consequently, these small differences in kinship have been considered inadequate to drive the evolution of mate choice, particularly by males. Even a small incremental difference in mate quality, however, may significantly affect male reproductive success, especially for monogamous species or those that require maternal care. This study has demonstrated that the social preferences of male oldfield mice are distributed between females according to small differences in their kinship to these potential mates. Copyright 2003 Published by Elsevier Science Ltd on behalf of The Association for the Study of Animal Behaviour [Copyright &y& Elsevier]

Presents a literary criticism on Vasily Aksenov's novel 'The Steel Bird.' Plot of the novel; Link of novel's protagonist Popenkov with Joseph Stalin; Language used in the novel; Characteristics of Popenkov's speech.

Evaluates the proportion of drug abuse related to opioid analgesics and the trends in medical use and abuse of five opioid analgesics used to treat severe pain. Analysis of data on opioid abuse from the Drug Abuse Warning Network (DAWN); Data on medical use of opioids from the United States Drug Enforcement Administration's Automation of Reports and Consolidated Orders System.

The purpose and activities of the Pain & Policy Studies Group (PPSG) at the University of Wisconsin are discussed, especially in its role as the World Health Organization Collaborating Center for Policy and Communications in Cancer Care. Issues relating to the need for balanced opioid policy, the International Narcotics Control Board, opioid availability, overly restrictive national laws and regulations, and specific examples of improvements that have resulted from work of the PPSG are described. [ABSTRACT FROM AUTHOR]

β 2 -adrenoceptors are G-protein coupled receptors expressed on both astrocytes and microglia that play a key role in mediating the anti-inflammatory actions of noradrenaline in the CNS. Here the effect of an inflammatory stimulus (LPS + IFN-γ) was examined on glial β 2 -adrenoceptor expression and function. Exposure of glia to LPS + IFN-γ decreased β 2 -adrenoceptor mRNA and agonist-stimulated production of the intracellular second messenger cAMP. Pre-treatment with the synthetic glucocorticoid and potent anti-inflammatory agent dexamethasone prevented the LPS + IFN-γ-induced suppression of β 2 -adrenoceptor mRNA expression. These results raise the possibility that inflammation-mediated β 2 -adrenoceptor downregulation in glia may dampen the innate anti-inflammatory properties of noradrenaline in the CNS. Unlabelled Image • LPS + IFN-γ reduces β 2 -adrenoceptor mRNA expression in primary rat mixed glia. • LPS + IFN-γ reduces β 2 -adrenoceptor agonist-induced cAMP response. • Dexamethasone prevents LPS + IFN-γ-induced suppression of β 2 -adrenoceptor expression. [ABSTRACT FROM AUTHOR]