Blue space interventions evidently have a positive impact on well-being and mental health, yet longitudinal studies on the lasting impact of such interventions are scarce. In this qualitative ...follow-up study with semi-structured interviews, we explored the long-term experiences over 18-42 months among six out of the initial eight women from the primary study, also including two instructors from the initial study. The participants, dealing with mental disorders, participated in the group-based intervention Freedom on Water, participating in stand-up paddling. Five main themes emerged from the empirical analysis: SUP as a catalyst for broadening horizons; learning: stepping out of the comfort zone; a break from diagnosis and rumination; connectedness to nature, specifically blue nature, and to the group; a life-changing journey; and a shift in mindset. The study revealed a long-term, life-changing impact of the program on participants' well-being and mental health. Nature and blue space activities had become a greater part of their lives, improving their mental health with feelings of calmness, positivity, healing, and freedom. Stepping out of their comfort zone facilitated experiences of success and transformed their mindsets. Moreover, they experienced a break from rumination, and they became more outwardly focused, with confidence in themselves and their abilities, while making new friendships and engaging in new and different contexts.
Self-regulation is pivotal for human well-being and mental health. In this qualitative study, we followed a randomized controlled trial (RCT) and explored how a five-day residential mindfulness ...program in a restorative natural setting supported self-regulation among university students experiencing moderate to severe stress. Six participants were interviewed post intervention and at three months' follow-up on how they experienced the retreat. Through interpretative phenomenological analysis, four interrelated themes emerged: "supportive conditions", "attitudes of mindfulness", "connection" and "physical and psychological balance." These themes reflected the outcomes of the retreat that participants valued in stressful situations. A progression occurred during the retreat through the themes, with emphasis developing from the supportive conditions of the setting, to cultivating mindful attitudes, over connection to both self, others and nature, to changes and effects on the physical, psychological and even spiritual level. In addition, participants emphasized experiences of positive emotions, energy, calmness, meta-awareness and the feeling of being part of the web of life. In conclusion, participants' experiences with a five-day nature-based mindfulness intervention revealed a range of qualities of both physical-, psychological-, social- and spiritual nature that are supportive for self-regulation.
MicroRNAs (miRNA) are a group of short noncoding RNAs that regulate gene expression at the posttranscriptional level. It has been shown that microRNAs are independent predictors of outcome in ...patients with diffuse large B-cell lymphoma (DLBCL) treated with the drug combination R-CHOP. Based on the measured growth inhibition of 60 human cancer cell lines (NCI60) in the presence of doxorubicine, cyclophosphamide, vincristine and etoposide as well as the baseline microRNA expression of the 60 cell lines, a microRNA based response predictor to CHOP was developed. The response predictor consisting of 20 microRNAs was blindly validated in a cohort of 116 de novo DLBCL patients treated with R-CHOP or R-CHOEP as first line treatment. The predicted sensitivity based on diagnostic FFPE samples matched the clinical response, with decreasing sensitivity in poor responders (P = 0.03). When the International Prognostic Index (IPI) was included in the prediction analysis, the separation between responders and non-responders improved (P = 0.001). Thirteen patients developed relapse, and five patients predicted sensitive to their second and third line treatment survived a median 1194 days, while eight patients predicted not sensitive to their second and third line treatment survived a median 187 days (90% CI: 485 days versus 227 days). Among the latter group it was predicted that four would have been sensitive to another second line treatment than the one they received. The predictions were almost the same when diagnostic biopsies were used as when relapse biopsies were used. These preliminary findings warrant testing in a larger cohort of relapse patients to confirm whether the miRNA based predictor can select the optimal second line treatment and increase survival.
miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response ...predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS).
The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS.
A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17-0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16-0.87)) and DSS (HR: 0.32 (0.12-0.87)).
The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer.
The NCI-60 panel of 60 human cancer cell-lines of nine different tissues of origin has been extensively characterized in biological, molecular and pharmacological studies. Analyses of data from such ...studies have provided valuable information for understanding cellular processes and developing strategies for the diagnosis and treatment of cancer. Here, Affymetrix® GeneChip™ miRNA version 1 oligonucleotide microarrays were used to quantify 847 microRNAs to generate an expression dataset of 495 (58.4%) microRNAs that were identified as expressed in at least one cell-line of the NCI-60 panel. Accuracy of the microRNA measurements was partly confirmed by reverse transcription and polymerase chain reaction assays. Similar to that seen among the four existing NCI-60 microRNA datasets, the concordance of the new expression dataset with the other four was modest, with mean Pearson correlation coefficients of 0.37-0.54. In spite of this, comparable results with different datasets were noted in clustering of the cell-lines by their microRNA expression, differential expression of microRNAs by the lines' tissue of origin, and correlation of specific microRNAs with the doubling-time of cells or their radiation sensitivity. Mutation status of the cell-lines for the TP53, PTEN and BRAF but not CDKN2A or KRAS cancer-related genes was found to be associated with changes in expression of specific microRNAs. The microRNA dataset generated here should be valuable to those working in the field of microRNAs as well as in integromic studies of the NCI-60 panel.
Here, we developed and examined a new way of disseminating mindfulness in nature to people without meditation experience, based on the finding that mindfulness conducted in natural settings may have ...added benefits. We evaluated a 5-day residential programme aiming to reduce stress and improve mental health outcomes. We compared an indoor and an outdoor version of the programme to a control group in a pilot randomised controlled trial (RCT). Sixty Danish university students experiencing moderate to high levels of stress were randomised into a residential mindfulness programme indoors (n = 20), in nature (n = 22), or a control group (n = 18). Participants completed the Perceived Stress Scale and the Self-Compassion Scale (primary outcomes) along with additional secondary outcome measures at the start and end of the program and 3 months after. Stress was decreased with small to medium effect sizes post-intervention, although not statistically significant. Self-compassion increased post-intervention, but effect sizes were small and not significant. At follow-up, changes in stress were not significant, however self-compassion increased for both interventions with medium-sized effects. For the intervention groups, medium- to large-sized positive effects on trait mindfulness after a behavioural task were found post-intervention, and small- to medium-sized effects in self-reported mindfulness were seen at follow-up. Connectedness to Nature was the only outcome measure with an incremental effect in nature, exceeding the control with a medium-sized effect at follow-up. All participants in the nature arm completed the intervention, and so did 97% of the participants in all three arms. Overall, the results encourage the conduct of a larger-scale RCT, but only after adjusting some elements of the programme to better fit and take advantage of the potential benefits of the natural environment.
Insulin resistance in skeletal muscle in type 2 diabetes (T2D) is characterized by more pronounced metabolic and molecular defects than in obesity per se. There is increasing evidence that adipose ...tissue dysfunction contributes to obesity-induced insulin resistance in skeletal muscle. Here, we used an unbiased approach to examine if adipose tissue dysfunction is exaggerated in T2D and linked to diabetes-related mechanisms of insulin resistance in skeletal muscle. Transcriptional profiling and biological pathways analysis were performed in subcutaneous adipose tissue (SAT) and skeletal muscle biopsies from 17 patients with T2D and 19 glucose-tolerant, age and weight-matched obese controls. Findings were validated by qRT-PCR and western blotting of selected genes and proteins. Patients with T2D were more insulin resistant and had lower plasma adiponectin than obese controls. Transcriptional profiling showed downregulation of genes involved in mitochondrial oxidative phosphorylation and the tricarboxylic-acid cycle and increased expression of extracellular matrix (ECM) genes in SAT in T2D, whereas genes involved in proteasomal degradation were upregulated in the skeletal muscle in T2D. qRT-PCR confirmed most of these findings and showed lower expression of adiponectin in SAT and higher expression of myostatin in muscle in T2D. Interestingly, muscle expression of proteasomal genes correlated positively with SAT expression of ECM genes but inversely with the expression of ADIPOQ in SAT and plasma adiponectin. Protein content of proteasomal subunits and major ubiquitin ligases were unaltered in the skeletal muscle of patients with T2D. A transcriptional signature of exaggerated adipose tissue dysfunction in T2D, compared with obesity alone, is linked to low plasma adiponectin and increased transcriptional activation of proteasomal degradation in skeletal muscle.
dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and ...hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-κB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment “niche.” Our findings also demonstrate a role for Dlk1 in mediating the immune response.
The investigation of treatment mechanisms in randomized controlled trials has considerable clinical and theoretical relevance. Despite the empirical support for the effect of mindfulness-based ...cognitive therapy (MBCT) in the treatment of recurrent major depressive disorder (MDD), the specific mechanisms by which MBCT leads to therapeutic change remain unclear.
By means of a systematic review we evaluate how the field is progressing in its empirical investigation of mechanisms of change in MBCT for recurrent MDD.
To identify relevant studies, a systematic search was conducted. Studies were coded and ranked for quality.
The search produced 476 articles, of which 23 were included. In line with the theoretical premise, 12 studies found that alterations in mindfulness, rumination, worry, compassion, or meta-awareness were associated with, predicted or mediated MBCT's effect on treatment outcome. In addition, preliminary studies indicated that alterations in attention, memory specificity, self-discrepancy, emotional reactivity and momentary positive and negative affect might play a role in how MBCT exerts its clinical effects.
The results suggest that MBCT could work through some of the MBCT model's theoretically predicted mechanisms. However, there is a need for more rigorous designs that can assess greater levels of causal specificity.
•Mindfulness-based cognitive therapy for recurrent major depression•A systematic review of 23 clinical trials investigating mechanisms of change•MBCT may work according to the theoretically proposed mechanisms.•Better designs that can assess greater causal specificity are needed.•We provide recommendations for future research.
Research has proven that both mindfulness training and exposure to nature have positive health effects. The purpose of this study was to systematically review quantitative studies of mindfulness ...interventions conducted in nature (nature-based mindfulness), and to analyze the effects through meta-analyses. Electronic searches revealed a total of 25 studies to be included, examining 2990 participants. Three analyses were conducted: Nature-based mindfulness interventions evaluated as open trials (k = 13), nature-based mindfulness compared with groups in non-active control conditions (k = 5), and nature-based mindfulness compared with similar interventions but without contact with nature (k = 7). The overall combined psychological, physiological, and interpersonal effects from pre- to post-intervention were statistically significant and of medium size (
= 0.54,
<
.001). Moderation analyses showed that natural environments characterized as forests/wild nature obtained larger numerical effects than environments characterized as gardens/parks, as did informal mindfulness compared with formal mindfulness. The small number of studies included, as well as the heterogeneity and generally low quality of the studies, must be taken into consideration when the results are interpreted. PROSPERO registration number: CRD42017065639.
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