Physical activity for treatment of irritable bowel syndrome.

BACKGROUND: Current recommendations for people with irritable bowel syndrome (IBS) to partake in physical activity are based on low-level evidence, do not incorporate evidence from all available randomised controlled trials (RCTs) and provide little information regarding potential adverse effects. OBJECTIVES: To assess the benefits and harms of physical activity interventions in adults diagnosed with irritable bowel syndrome and to explore possible effect moderators including type, setting and nature of physical activity interventions. SEARCH METHODS: We searched nine electronic databases including CENTRAL, MEDLINE and Embase to 5 November 2021. We handsearched reference lists and sought unpublished studies through trial registries. SELECTION CRITERIA: We included RCTs involving adults (aged 18 years or older) diagnosed with IBS and conducted in any setting comparing a physical activity intervention with no intervention, usual care or wait-list control group or another physical activity intervention group and assessing a validated measure of symptoms, quality of life or bowel movement. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence. We pooled studies that evaluated similar outcomes using a random-effects meta-analysis, and synthesised data from other studies narratively. MAIN RESULTS: We included 11 RCTs with data for 622 participants. Most (10/11) were set in high- or middle- to high-income countries, with five involving supervised physical activity, three unsupervised activity and three a mix of supervised and unsupervised activity. No trial was at low risk of bias. Four trials specified a minimally important difference for at least one assessed outcome measure. Data for 10 trials were obtained from published journal articles, with data for one obtained from an unpublished Masters degree thesis. Irritable bowel syndrome symptoms Six RCTs assessed the effectiveness of a physical activity intervention compared with usual care on global symptoms of IBS. Meta-analysis of five studies showed an observed improvement in reported symptoms following physical activity (standardised mean difference (SMD) -0.93, 95% confidence interval (CI) -1.44 to -0.42; 185 participants). We rated the certainty of evidence for this outcome as very low due to unclear and high risk of bias, inconsistency and imprecision from sparse data. This means physical activity may improve IBS symptoms but the evidence is very uncertain. The results of the remaining study supported the meta-analysis but were at unclear risk of bias and sample size was small. Two studies assessed the effectiveness of a yoga intervention compared with a walking intervention on global IBS symptoms. Meta-analysis of these two studies found no conclusive evidence of an effect of yoga compared with walking on IBS symptoms (SMD -1.16, 95% CI -3.93 to 1.62; 124 participants). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of yoga interventions compared with walking interventions on IBS symptoms. Two studies assessed the effectiveness of a physical activity intervention (yoga) compared with medication. One reported no observed difference in global IBS symptoms, though CIs were wide, suggesting uncertainty in the observed estimates and risk of bias was high (MD -1.20, 95% CI -2.65 to 0.25; 21 participants). We excluded IBS symptom data for the remaining study as it used a non-validated method. One study compared a yoga intervention with a dietary intervention and reported an observed improvement in symptoms with both interventions but neither intervention was superior to the other. Quality of life Five RCTs assessed the impact of physical activity on self-reported quality of life compared with usual care. Meta-analysis of data from four studies found no improvement in quality of life following a physical activity intervention (SMD 1.17, 95% CI -0.30 to 2.64; 134 participants; very low certainty due to risk of bias, inconsistency and imprecision). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of physical activity interventions on quality-of-life outcomes in people with IBS. One study assessed the impact on quality of life of a yoga intervention compared with walking and observed an improvement in the yoga group (MD 53.45, 95% CI 38.85 to 68.05; 97 participants ).  One study reported no observed difference in quality of life between a yoga and a dietary intervention. Abdominal pain Two trials assessed the impact of physical activity compared with usual care on reported abdominal pain. Meta-analysis found no improvement in abdominal pain with physical activity compared with usual care (SMD 0.01, 95% CI -0.48 to 0.50; 64 participants). We rated the certainty of the evidence as very low due to risk of bias and imprecision, meaning the evidence is very uncertain about the effect of physical activity interventions on abdominal pain in people with IBS. One study assessing the impact of a yoga intervention compared with walking advice reported no observed differences between groups on abdominal pain. One study comparing a yoga intervention with a dietary intervention found neither intervention had a more beneficial impact than the other and both interventions did not conclusively reduce abdominal pain. There was insufficient evidence to adequately assess adverse effects associated with physical activity due to a lack of reporting in trials. One study reported a musculoskeletal injury in a yoga intervention group but this did not result in withdrawal from the study. AUTHORS' CONCLUSIONS: Findings from a small body of evidence suggest that physical activity comprising of yoga, treadmill exercise or support to increase physical activity may improve symptoms but not quality of life or abdominal pain in people diagnosed with IBS but we have little confidence in these conclusions due to the very low certainty of evidence. The numbers of reported adverse events were low and the certainty of these findings was very low for all comparisons, so no conclusions can be drawn. Discussions with patients considering physical activity as part of symptom management should address the uncertainty in the evidence to ensure fully informed decisions. If deemed sufficiently important to patients and healthcare providers, higher quality research is needed to enable more certain conclusions.

Exploring peer specialists' experiences with spirituality in their work: Recommendations for future directions.

OBJECTIVE: Spirituality is part of recovery for many people with lived experience of mental health issues, including those who become peer specialists and utilize their own recovery experiences to facilitate the recovery of others. This research explores how peer specialists view spirituality in their work with their peers and the factors that impact conversations in this area. METHOD: Eleven peer specialists participated in individual qualitative interviews. Inquiries were made about their own experiences of spirituality and how these were used to support others. Additional questions probed factors that facilitated or served as barriers to their ability to engage in such conversations. Data were subjected to thematic analysis. RESULTS: Peer specialists experienced well-being, hope, and self-acceptance through spirituality. Use of spirituality in peer support was influenced by their personal spiritual journey, specifically because they understood its value to recovery. Barriers to use included fear of rejection and lack of formal support. The number one facilitator was their personal experience, but they suggested the need for training and guidelines as important future facilitators. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Results indicate that at least some peer specialists are thinking about the role of spirituality in their work but express some struggles with such activities. There appears a need for guidelines on how to use spirituality in peer support, better definitions of the competencies peer specialists need, and more attention to training and supervision in this area-possibly to maximize the benefit of the lived experience that many peer specialists bring to their work. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Spatial relationship between well water arsenic and uranium in Northern Plains native lands.

Arsenic and uranium in unregulated private wells affect many rural populations across the US. The distribution of these contaminants in the private wells of most American Indian communities is poorly characterized, and seldom studied together. Here, we evaluate the association between drinking water arsenic and uranium levels in wells (n = 441) from three tribal regions in North Dakota and South Dakota participating in the Strong Heart Water Study. Groundwater contamination was extensive; 29% and 7% of wells exceeded maximum contaminant levels for arsenic and uranium respectively. 81% of wells had both arsenic and uranium concentrations at one-tenth of their human-health benchmark (arsenic, 1 µg/L; uranium 3 µg/L). Well arsenic and uranium concentrations were uncorrelated (rs = 0.06); however, there appeared to be a spatial correlation of wells co-contaminated by arsenic and uranium associated with flow along a geologic contact. These findings indicate the importance of measuring multiple metals in well water, and to understand underlying hydrogeological conditions. The underlying mechanisms for the prevalence of arsenic and uranium across Northern Plains Tribal Lands in the US, and in particular the occurrence of both elevated arsenic and uranium in drinking water wells in this region, demands further study.

Ancient plant DNA reveals High Arctic greening during the Last Interglacial.

Summer warming is driving a greening trend across the Arctic, with the potential for large-scale amplification of climate change due to vegetation-related feedbacks [Pearson et al., Nat. Clim. Chang. (3), 673-677 (2013)]. Because observational records are sparse and temporally limited, past episodes of Arctic warming can help elucidate the magnitude of vegetation response to temperature change. The Last Interglacial ([LIG], 129,000 to 116,000 y ago) was the most recent episode of Arctic warming on par with predicted 21st century temperature change [Otto-Bliesner et al., Philos. Trans. A Math. Phys. Eng. Sci. (371), 20130097 (2013) and Post et al., SciAdv (5), eaaw9883 (2019)]. However, high-latitude terrestrial records from this period are rare, so LIG vegetation distributions are incompletely known. Pollen-based vegetation reconstructions can be biased by long-distance pollen transport, further obscuring the paleoenvironmental record. Here, we present a LIG vegetation record based on ancient DNA in lake sediment and compare it with fossil pollen. Comprehensive plant community reconstructions through the last and current interglacial (the Holocene) on Baffin Island, Arctic Canada, reveal coherent climate-driven community shifts across both interglacials. Peak LIG warmth featured a ∼400-km northward range shift of dwarf birch, a key woody shrub that is again expanding northward. Greening of the High Arctic-documented here by multiple proxies-likely represented a strong positive feedback on high-latitude LIG warming. Authenticated ancient DNA from this lake sediment also extends the useful preservation window for the technique and highlights the utility of combining traditional and molecular approaches for gleaning paleoenvironmental insights to better anticipate a warmer future.

Notoginsenoside R1 Protects Against the Acrylamide-Induced Neurotoxicity via Upregulating Trx-1-Mediated ITGAV Expression: Involvement of Autophagy.

Acrylamide (ACR) is a common chemical used in various industries and it said to have chronic neurotoxic effects. It is produced during tobacco smoking and is also generated in high-starch foods during heat processing. Notoginsenoside R1 (NR1) is a traditional Chinese medicine, which is used to improve the blood circulation and clotting. The objective of this study was to investigate the mechanism of ACR-triggered neurotoxicity and to identify the protective role of NR1 by upregulating thioredoxin-1 (Trx-1). Our results have shown that NR1 could block the spatial and cognitive impairment caused by ACR administration. Bioinformatics analysis revealed that Trx-1 regulated autophagy via Integrin alpha V (ITGAV). NR1 could resist the ACR-induced neurotoxicity by upregulating thioredoxin-1 in PC12 cells and mice. The autophagy-related proteins like autophagy-related gene (ATG) 4B, Cathepsin D, LC3 II, lysosomal-associated membrane protein 2a (LAMP2a), and ITGAV were restored to normal levels by NR1 treatment in both PC12 cells and mice. Besides, we also found that overexpression of Trx-1 resisted ACR-induced autophagy in PC12 cells and downregulation of Trx-1 triggered autophagy induced by ACR in PC12 cells. Therefore, it could be concluded that Trx-1 was involved in the autophagy pathway. Besides, we also found that ITGAV was an intermediate node linking Trx-1 and the autophagy pathway.

Mindfulness-Oriented Recovery Enhancement Restructures Reward Processing and Promotes Interoceptive Awareness in Overweight Cancer Survivors: Mechanistic Results From a Stage 1 Randomized Controlled Trial.

INTRODUCTION: The primary aims of this Stage I pilot randomized controlled trial were to establish the feasibility of integrating exercise and nutrition counseling with Mindfulness-Oriented Recovery Enhancement (MORE), a novel intervention that unites training in mindfulness, reappraisal, and savoring skills to target mechanisms underpinning appetitive dysregulation a pathogenic process that contributes to obesity among cancer survivors; to identify potential therapeutic mechanisms of the MORE intervention; and to obtain effect sizes to power a subsequent Stage II trial. METHODS: Female overweight and obese cancer survivors (N = 51; mean age = 57.92 ± 10.04; 88% breast cancer history; 96% white) were randomized to one of two 10-week study treatment conditions: ( a) exercise and nutrition counseling or ( b) exercise and nutrition counseling plus the MORE intervention. Trial feasibility was assessed via recruitment and retention metrics. Measures of therapeutic mechanisms included self-reported interoceptive awareness, maladaptive eating behaviors, and savoring, as well as natural reward responsiveness and food attentional bias, which were evaluated as psychophysiological mechanisms. RESULTS: Feasibility was demonstrated by 82% of participants who initiated MORE receiving a full dose of the intervention. Linear mixed models revealed that the addition of MORE led to significantly greater increases in indices of interoceptive awareness, savoring, and natural reward responsiveness, and, significantly greater decreases in external eating behaviors and food attentional bias-the latter of which was significantly associated with decreases in waist-to-hip ratio. Path analysis demonstrated that the effect of MORE on reducing food attentional bias was mediated by increased zygomatic electromyographic activation during attention to natural rewards. CONCLUSIONS AND IMPLICATIONS: MORE may target appetitive dysregulatory mechanisms implicated in obesity by promoting interoceptive awareness and restructuring reward responsiveness.

Randomized Controlled Trial of Brief Mindfulness Training and Hypnotic Suggestion for Acute Pain Relief in the Hospital Setting.

BACKGROUND: Medical management of acute pain among hospital inpatients may be enhanced by mind-body interventions. OBJECTIVE: We hypothesized that a single, scripted session of mindfulness training focused on acceptance of pain or hypnotic suggestion focused on changing pain sensations through imagery would significantly reduce acute pain intensity and unpleasantness compared to a psychoeducation pain coping control. We also hypothesized that mindfulness and suggestion would produce significant improvements in secondary outcomes including relaxation, pleasant body sensations, anxiety, and desire for opioids, compared to the control condition. METHODS: This three-arm, parallel-group randomized controlled trial conducted at a university-based hospital examined the acute effects of 15-min psychosocial interventions (mindfulness, hypnotic suggestion, psychoeducation) on adult inpatients reporting "intolerable pain" or "inadequate pain control." Participants (N = 244) were assigned to one of three intervention conditions: mindfulness (n = 86), suggestion (n = 73), or psychoeducation (n = 85). KEY RESULTS: Participants in the mind-body interventions reported significantly lower baseline-adjusted pain intensity post-intervention than those assigned to psychoeducation (p < 0.001, percentage pain reduction: mindfulness = 23%, suggestion = 29%, education = 9%), and lower baseline-adjusted pain unpleasantness (p < 0.001). Intervention conditions differed significantly with regard to relaxation (p < 0.001), pleasurable body sensations (p = 0.001), and desire for opioids (p = 0.015), but all three interventions were associated with a significant reduction in anxiety (p < 0.001). CONCLUSIONS: Brief, single-session mind-body interventions delivered by hospital social workers led to clinically significant improvements in pain and related outcomes, suggesting that such interventions may be useful adjuncts to medical pain management. TRIAL REGISTRATION: Trial Registry: ClinicalTrials.gov ; registration ID number: NCT02590029 URL: https://clinicaltrials.gov/ct2/show/NCT02590029.

Pain, hedonic regulation, and opioid misuse: Modulation of momentary experience by Mindfulness-Oriented Recovery Enhancement in opioid-treated chronic pain patients.

BACKGROUND: Given the risk of opioid misuse among chronic pain patients being treated with long-term opioid pharmacotherapy, non-pharmacological treatments are needed. Further, in light of hedonic deficits in this population, therapies that enhance positive affect may be useful. The purpose of this study was to examine effects of a Mindfulness-Oriented Recovery Enhancement (MORE) intervention on ecological momentary assessments (EMA) of pain and positive affective experience, and to determine if changes in pain, affect, and their interaction were associated with opioid misuse at post-treatment. METHODS: This study examined unpublished EMA data from a subset of participants (N=55) in a previously published RCT (NCT01505101) of MORE versus a support group (SG) control. Across 8 weeks of treatment, patients completed up to 224 EMA measures of pain and affect. Multilevel models and generalized estimating equations examined effects of treatment on momentary pain and positive affect, and generalized linear models examined associations between pain and affect and changes in opioid misuse by post-treatment. RESULTS: Patients in MORE reported significantly greater improvements in momentary pain (p=0.01) and positive affect (p=0.004) than patients in the SG. Further, over the entire course of treatment, patients in MORE were significantly more likely to exhibit positive affect regulation (OR=2.75) than patients in the SG. Finally, improvements in positive affect (but not pain) over the course of intervention were associated with reduced risk of misusing opioids by post-treatment (p=0.02). CONCLUSION: MORE may be a useful non-pharmacological treatment for pain and hedonic deficits among chronic pain patients at risk for opioid misuse.

Mindfulness is Associated With Increased Hedonic Capacity Among Chronic Pain Patients Receiving Extended Opioid Pharmacotherapy.

OBJECTIVES: Chronic pain and long-term opioid use may lead to a persistent deficit in hedonic capacity, characterized by increased sensitivity to aversive states and insensitivity to natural rewards. Dispositional mindfulness has been linked with improved emotion regulation and pain coping. The aim of the current study was to examine associations between dispositional mindfulness, hedonic capacity, and pain-related interference in an opioid-using chronic pain sample. METHODS: Data were obtained from a sample of 115 chronic pain patients on long-term opioid therapy (68% females, M age=48.3, SD=13.6) who completed the Five Facet Mindfulness Questionnaire (FFMQ), the Snaith-Hamilton Anhedonia and Pleasure Scale (SHAPS), the Brief Pain Inventory, and a psychiatric assessment of major depression. Bivariate correlations, hierarchical multiple regression, and path analysis were used to determine whether dispositional mindfulness scores (FFMQ) predicted variance in hedonic capacity (SHAPS), and whether hedonic capacity mediated the association between mindfulness and pain interference. RESULTS: We observed a significant positive correlation between dispositional mindfulness and hedonic capacity scores (r=0.33, P<0.001). Hierarchical regression indicated that after controlling for pain interference and major depressive disorder diagnosis, dispositional mindfulness explained a significant portion of variance in hedonic capacity (ß=0.30, P<0.01). The association between dispositional mindfulness and pain interference was mediated by hedonic capacity (b=-0.011, SE=0.005; 95% CI, -0.004 to -0.024, full model R=0.39). DISCUSSION: Findings indicate that dispositional mindfulness was associated with hedonic capacity among this chronic pain sample. In light of this association, it is plausible that interventions that increase mindfulness may reduce pain-related impairment among opioid-using patients by enhancing hedonic capacity.

Linking dispositional mindfulness and positive psychological processes in cancer survivorship: a multivariate path analytic test of the mindfulness-to-meaning theory.

BACKGROUND: Research indicates that dispositional mindfulness is associated with positive psychological functioning. Although this disposition has been linked with beneficial outcomes in the broader mental health literature, less is known about dispositional mindfulness in cancer survivors and how it may be linked with indices of psychological and physical health relevant to cancer survivorship. METHODS: We conducted a multivariate path analysis of data from a heterogeneous sample of cancer patients (N = 97) to test the Mindfulness-to-Meaning Theory, an extended process model of emotion regulation linking dispositional mindfulness with cancer-related quality of life via positive psychological processes. RESULTS: We found that patients endorsing higher levels of dispositional mindfulness were more likely to pay attention to positive experiences (ß = .56), a tendency which was associated with positive reappraisal of stressful life events (ß = .51). Patients who engaged in more frequent positive reappraisal had a greater sense of meaning in life (ß = .43) and tended to savor rewarding or life affirming events (ß = .50). In turn, those who engaged in high levels of savoring had better quality of life (ß = .33) and suffered less from emotional distress (ß = -.54). CONCLUSIONS: Findings provide support for the Mindfulness-to-Meaning Theory and help explicate the processes by which mindfulness promotes psychological flourishing in the face of cancer. IMPLICATIONS FOR CANCER SURVIVORSHIP: Cancer survivors may benefit from enhancing mindfulness, reappraisal, and savoring. Copyright © 2016 John Wiley & Sons, Ltd.

Extract of Vernonia condensata, Inhibits Tumor Progression and Improves Survival of Tumor-allograft Bearing Mouse.

Medicinal plants are considered as one of the ideal sources for cancer therapy due to their bioactive contents and low toxicity to humans. Vernonia genus is one of the common medicinal plants, which has wide spread usage in food and medicine. However, there are limited studies to explore its anticancer properties. In the current study, we have used Vernonia condensata, to explore its anticancer activity using various approaches. Here, we show that extract prepared from Vernonia condensata (VCE) exhibits cytotoxic properties against various cancer cells in a dose- and time-dependent manner. Interestingly, when treated with VCE, there was no significant cytotoxicity in peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis revealed that although VCE induced cell death, arrest was not observed. VCE treatment led to disruption of mitochondrial membrane potential in a concentration dependent manner resulting in activation of apoptosis culminating in cell death. Immunoblotting studies revealed that VCE activated intrinsic pathway of apoptosis. More importantly, VCE treatment resulted in tumor regression leading to significant enhancement in life span in treated mice, without showing any detectable side effects. Therefore, for the first time our study reveals the potential of extract from Vernonia condensata to be used as an anticancer agent.

Preclinical Characterization and In Vivo Efficacy of GSK8853, a Small-Molecule Inhibitor of the Hepatitis C Virus NS4B Protein.

The hepatitis C virus (HCV) NS4B protein is an antiviral therapeutic target for which small-molecule inhibitors have not been shown to exhibit in vivo efficacy. We describe here the in vitro and in vivo antiviral activity of GSK8853, an imidazo[1,2-a]pyrimidine inhibitor that binds NS4B protein. GSK8853 was active against multiple HCV genotypes and developed in vitro resistance mutations in both genotype 1a and genotype 1b replicons localized to the region of NS4B encoding amino acids 94 to 105. A 20-day in vitro treatment of replicons with GSK8853 resulted in a 2-log drop in replicon RNA levels, with no resistance mutation breakthrough. Chimeric replicons containing NS4B sequences matching known virus isolates showed similar responses to a compound with genotype 1a sequences but altered efficacy with genotype 1b sequences, likely corresponding to the presence of known resistance polymorphs in those isolates. In vivo efficacy was tested in a humanized-mouse model of HCV infection, and the results showed a 3-log drop in viral RNA loads over a 7-day period. Analysis of the virus remaining at the end of in vivo treatment revealed resistance mutations encoding amino acid changes that had not been identified by in vitro studies, including NS4B N56I and N99H. Our findings provide an in vivo proof of concept for HCV inhibitors targeting NS4B and demonstrate both the promise and potential pitfalls of developing NS4B inhibitors.

Low dispositional mindfulness predicts self-medication of negative emotion with prescription opioids.

OBJECTIVES: Although evidence is mounting that opioids are abused to self-medicate negative emotions, little is known about the traits and factors linked to opioid self-medication. One potentially crucial psychological correlate is dispositional mindfulness. Thus, the purpose of this study was to describe the prevalence of opioid self-medication among a treatment-seeking sample of prescription opioid-dependent individuals and specifically examine the relationship between dispositional mindfulness and opioid self-medication. METHODS: Participants in acute detoxification or intensive outpatient treatment for prescription opioid dependence (n = 79) were recruited from a regional hospital's addictions treatment unit for this cross-sectional study. Sociodemographic data were collected along with surveys of opioid self-medication, pain level, and dispositional mindfulness. RESULTS: Self-medication of negative affective states with opioids was quite common, with 94.9% of individuals sampled reporting self-medication behaviors. In adjusted analyses, individuals engaging in more frequent opioid use tended to self-medicate negative emotions with opioids more often than those engaging in more intermittent opioid use (ß = 0.33; P < 0.05). Importantly, irrespective of opioid use frequency and other clinical and sociodemographic covariates, dispositional mindfulness was inversely associated with opioid self-medication (ß = -0.42; P < 0.001), such that less mindful individuals reported using opioids more frequently to self-medicate negative emotions. CONCLUSIONS: Self-medication of negative emotions with opioids was prevalent in this sample and related to low dispositional mindfulness. Plausibly, increasing mindfulness may decrease opioid self-medication. Addictive automaticity and emotion regulation are discussed as potential mechanisms linking low dispositional mindfulness and self-medication.

Mindfulness-oriented recovery enhancement ameliorates the impact of pain on self-reported psychological and physical function among opioid-using chronic pain patients.

CONTEXT: Chronic pain impacts one-third of the U.S. population, and its effects are debilitating for individuals and costly to the medical system. Although opioids are commonly prescribed to address chronic pain, they confer risk for misuse and addiction in some patients and may not fully restore life function-particularly with regard to psychosocial factors. Because of the multiplicity of impacts that chronic pain may have on daily functioning, broad-spectrum behavioral interventions are needed. OBJECTIVES: The purpose of this study was to conduct follow-up analyses from a pilot randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE) to assess specific effects of MORE on various biopsychosocial aspects of pain-related impairment. METHODS: Chronic pain patients (N = 115; mean age, 48 ± 14 years; 68% female) were randomly assigned to either eight weeks of MORE or a support group. Domains of pain-related functional interference were measured with the Brief Pain Inventory at pre- and post-treatment and at a three-month follow-up. Treatment effects were analyzed with multivariate intention-to-treat models. RESULTS: MORE participants reported significantly greater reductions in functional interference than support group participants at post-treatment across all domains, including general activity, mood, walking ability, normal work, relationships, sleep, and enjoyment of life. These effects were largely maintained by the three-month follow-up; however, general activity level and walking ability were no longer significant, indicating differential long-term effects between physiological and psychological functioning. CONCLUSION: Findings demonstrate preliminary efficacy of MORE as a treatment for pain-related functional impairments and suggest that effects may be more pronounced and durable for aspects of psychological function.

The impact of oligofructose on stimulation of gut hormones, appetite regulation and adiposity.

OBJECTIVE: To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers. METHODS: In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day(-1) oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation. RESULTS: Oligofructose increased breath hydrogen (P < 0.0001), late acetate concentrations (P = 0.024), tended to increase total area under the curve (tAUC)420 mins peptide YY (PYY) (P = 0.056) and reduced tAUC450 mins hunger (P = 0.034) and motivation to eat (P = 0.013) when compared with cellulose. However, there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 (GLP-1) (P = 0.006) in the cellulose group and a decrease in EI during ad libitum meal in both groups. CONCLUSIONS: Oligofructose increased plasma PYY concentrations and suppressed appetite, while cellulose increased GLP-1 concentrations. EI decreased in both groups. However, these positive effects did not translate into changes in BW or adiposity.

Place knowing of persons and populations: restoring the place work of nursing.

Place emerges when space acquires definition in social constructions of meaning as landscape-languages, which reflect assumptions about physical and social realities. The place work of nursing, which resonated throughout Nightingale's work and the profession's evolution, focuses on human health and healing in the historical transitions and landscape-languages of populations. However, evidence-based practice dominated by empirical knowing inadequately addresses complex health and illness dynamics between place and populations. Translating evidence to the life course experiences of individuals and populations requires place knowing of human situated embodiment within discrete space. An exploration of the concept of place, its application to nursing, and the need for a place paradigm for practice is presented. A sense of salience and situated cognition has been identified as the essential element of the transformation needed in the education of nurses. Place knowing integrates other patterns of knowing (empirical, ethical, aesthetical, personal, unknowing, sociopolitical, and emancipatory) in a situated cognition. Place knowing, like other established patterns of knowing, is a significant epistemological foundation of nursing. Place knowing allows the nuanced intricately complex dynamics of embodied situated human health and illness to be examined, the salience of the particulars to be considered, and the whole of the landscape-languages to emerge.

SAR and biological evaluation of novel trans-3,4-dimethyl-4-arylpiperidine derivatives as opioid antagonists.

The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. We have developed a SAR study around LY255582 by comparing the effect of the hydroxy group in the 2- and 4-position of the phenyl ring. Also, we have proved that the 3-position of the phenyl ring is optimal for opioid activity. Furthermore, we have successfully replaced the hydroxy group in LY255582 by carbamate and carboxamide groups. The new analogs have high affinity for the opioid receptors comparable to the corresponding phenol. Carboxamide analog 12 has an improved metabolism profile and proved to be efficacious in in vivo studies.

A new UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase mRNA exhibits predominant expression in the hypothalamus, thalamus and amygdala of mouse forebrain.

Protein glycosylation is a common and important process that can alter the stability, half-life, biological activity and receptor recognition of target molecules. We have identified a new putative mouse UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family member, termed GalNAc-T10/ppGaNTase-T10 (gene symbol Galnt10), and determined its expression pattern in mouse CNS using in situ hybridization analysis. Results demonstrated predominant expression of Galnt10 in several distinct hypothalamic, thalamic and amygdaloid nuclei. The most abundant hybridization levels were observed in the paraventricular, ventromedial and arcuate nuclei of the hypothalamus, the anterodorsal and parafascicular nuclei of the thalamus and the central, basomedial and medial nuclei of the amygdala. Expression of Galnt10 was also detected in cerebral cortex, lateral septum, habenula and hippocampus. The localization of this putative glycosyltransferase in distinct regions within the CNS indicates the specificity for complex protein modifications and suggests that region-specific glycosylation represents an essential process in basic biological functions.