Efficacy of nature-based therapy for individuals with stress-related illnesses: randomised controlled trial.

BACKGROUND: Stress-related illnesses are a major threat to public health, and there is increasing demand for validated treatments.AimsTo test the efficacy of nature-based therapy (NBT) for patients with stress-related illnesses. METHOD: Randomised controlled trial (ClinicalTrials.gov ID NCT01849718) comparing Nacadia® NBT (NNBT) with the cognitive-behavioural therapy known as Specialised Treatment for Severe Bodily Distress Syndromes (STreSS). In total, 84 participants were randomly allocated to one of the two treatments. The primary outcome measure was the mean aggregate score on the Psychological General Well-Being Index (PGWBI). RESULTS: Both treatments resulted in a significant increase in the PGWBI (primary outcome) and a decrease in burnout (the Shirom-Melamed Burnout Questionnaire, secondary outcome), which were both sustained 12 months later. No significant difference in efficacy was found between NNBT and STreSS for primary outcome and secondary outcomes. CONCLUSIONS: The study showed no statistical evidence of a difference between NNBT and STreSS for treating patients with stress-related illnesses.Declaration of interestNone.

Nature-Based Therapeutic Intervention for Individuals with Post-Concussion Symptoms.

This study investigated the efficacy of a 10-session nature-based therapeutic intervention for people with post-concussion symptoms. The intervention involved physical and vestibular exercises, sensory training, relaxation, and psychoeducation, all of which were integrated with the natural environment in a forest therapy garden. This study was designed with a passive control period followed by the intervention (n = 30). The Mental Fatigue Scale (MFS) was the primary outcome measure. The secondary outcome measures were the Warwick-Edinburg Mental Wellbeing Scale and the short version of the Quality of Life after Brain Injury. A Likert scale was used to examine the mental strain of the sessions themselves. The MFS (primary outcome) exhibited a significant decrease with a medium-sized effect from before to after the intervention. The secondary outcomes exhibited significant increases from the beginning to the end of the intervention. All outcomes were sustained at follow-up ten weeks later. No significant difference was found from the control period. This study indicates that the described nature-based intervention is a feasible treatment for reducing prolonged post-concussion symptoms. However, it should be studied more in-depth to understand the impact of the natural environment and to validate the results on a larger representative population.

Psycho-Physiological Stress Recovery in Outdoor Nature-Based Interventions: A Systematic Review of the Past Eight Years of Research.

BACKGROUND: In modern, urban daily life, natural environments are increasingly recognized as an important resource for stress recovery and general well-being. AIM: the present review aims to provide an overview and synthesis of the past eight years' research into the psycho-physiological effects of outdoor nature-based interventions, related to stress recovery. METHOD: a structured search was performed in seven databases, returning 5618 articles. Removal of duplicates and initial screening gave a total of 95 studies. After full text reading, 36 studies were included in the assessment. RESULTS: most of the psychological outcomes were related to different emotional measures. The synthesis of the results points towards outdoor, nature-based exposure having a positive effect on different emotional parameters, related to stress relief. The studies into physiological measures showed more equivocal results. CONCLUSION: the research, conducted over the past eight years, into outdoor, nature-based exposure has now attained a sound evidence base for psychological and especially emotional effects, but the evidence base for physiological effects within this timeframe shows a great degree of heterogeneity. LIMITATIONS: interpretation of the results is limited by the review only covering the past eight years' research on the subject.

Post-Occupancy Evaluation of a Crisis Shelter Garden and Application of Findings Through the Use of a Participatory Design Process.

OBJECTIVE: This study concerned optimization of an evidence-based crisis shelter garden as a setting for everyday activities and nature-based therapy. The study hereby tested the design guidelines that the garden is based on. BACKGROUND: Design guidelines for gardens intended to support health are becoming increasingly specialized, targeting different user groups. This study contributes to the knowledge concerning health-supporting garden design at crisis shelters for women and children who are exposed to domestic violence. METHOD: The study included a post-occupancy evaluation (POE) consisting of landscape analyses, observation of physical traces, and interviews as well as a subsequent participatory design process. RESULTS: The landscape analyses and the observation of physical traces indicated a minimal level of maintenance and recurrent use being limited to a few areas of the garden. The interviews added nuance and new issues to these results, resulting in the following themes: maintenance, accessibility, safety, therapeutic setting and free space, many ways to play, and social and private spheres. The participatory design process led to an optimization of the garden, including changes to its physical design related to making the garden safer, positively distractive, and more versatile in terms of activities. Improvements were also made regarding policy for use, maintenance, and informing users. CONCLUSION: The design guidelines were tested, and the evidence was strengthened, adding nuance and new issues to consider during further development of the guidelines. Both the POE and the participatory design process were confirmed as crucial aspects of evidence-based health design.

Determination of leukocyte DNA 6-thioguanine nucleotide levels by high-performance liquid chromatography with fluorescence detection.

A HPLC method for determination of 6-thioguanine nucleotide in DNA was developed. Leukocyte DNA was isolated from peripheral blood, derivatized with chloroacetaldehyde and the formed etheno derivatives N(2),3-etheno 6-thioguanine (epsilon6TG), 1,N(6)-etheno adenine (epsilonA) and N(2),3-etheno guanine (epsilonG) were released from the DNA backbone by hydrolysis at pH 6.0 and 80 degrees C for 60 min. After extraction of epsilon6TG by immobilized metal ion affinity chromatography (IMAC) the sample was analysed by ion-pair reversed-phase HPLC with fluorescence detection. The limit of quantification was 9.0 nM and the intra- and interday precision ranged from 2.8 to 15.5%. In a small cohort of eight children with acute lymphoblastic leukaemia (ALL), a median of one 6-thioguanine base was found for each 3000 normal bases (range 1:2000-1:11000).

The Tree Is My Anchor: A Pilot Study on the Treatment of BED through Nature-Based Therapy.

Binge eating disorder (BED), characterized by recurrent episodes of binge eating with a subjective experience of lack of control, is the world's most common eating disorder. The aim of the present pilot study was to examine the feasibility of implementing nature-based therapy (NBT) in the treatment of BED. The NBT intervention was compared to Support Group Meetings (SGMs), which are the only publicly available form of support for people diagnosed with BED in Denmark. Twenty participants with a BED diagnosis were included in the study, which had a mixed-methods design including Eating Disorder Examination interviews, semi-structured interviews, and questionnaires measuring well-being (The Psychological General Well-Being Index) and self-esteem (Rosenberg's Self-Esteem Scale). Both the NBT and the SGMs showed positive results on all outcome measures (decreases in binge eating episodes and increases in general psychological well-being and self-esteem). The interviews indicated that the NBT context made the psychotherapeutic content more accessible to the participants and further helped them transfer the therapeutic gains to daily life after completing treatment. However, these results should be interpreted with caution due to the small sample size-ideally, they would need to be tested on a larger, randomized sample.

A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and Sick-Leave Absence: A Randomized Controlled Trial.

Stress-related illnesses are a growing health problem in the Western world; which also has economic significance for society. As a consequence; there is a growing demand for effective treatments. The study investigates the long-term efficacy of the Nacadia® nature-based therapy (NNBT) by comparing it to the efficacy of a validated cognitive behavioral therapy, called STreSS. The study is designed as a randomized controlled trial in which 84 participants are randomly allocated between the treatments. Long-term efficacy is investigated through data extracts from the national database of Statistics Denmark on the sick leave and the health-care consumption. The results show that both the NNBT and the STreSS lead to a significant decrease in number of contacts with a general practitioner in the period from twelve months prior to treatment to twelve months after treatment; and, a significant decrease in long-term sick leave from the month prior to treatment to twelve months after treatment. The positive long-term effects provide validation for the NNBT as an efficient treatment of stress-related illnesses.

A Diagnostic Post-Occupancy Evaluation of the Nacadia® Therapy Garden.

The design of the Nacadia® therapy garden is based on a model for evidence-based health design in landscape architecture (EBHDL). One element of the model is a diagnostic post-occupancy evaluation (DPOE), which has not previously been fully developed. The present study develops a generic DPOE for therapy gardens, with a focus on studying the effects of the design on patients' health outcomes. This is done in order to identify successes and failures in the design. By means of a triangulation approach, the DPOE employs a mixture of methods, and data is interpreted corroborating. The aim of the present study is to apply the DPOE to the Nacadia® therapy garden. The results of the DPOE suggest that the design of the Nacadia® therapy garden fulfills its stated aims and objectives. The overall environment of the Nacadia ® therapy garden was experienced as protective and safe, and successfully incorporated the various elements of the nature-based therapy programme. The participants encountered meaningful spaces and activities which suited their current physical and mental capabilities, and the health outcome measured by EQ-VAS (self-estimated general health) indicated a significant increase. Some design failures were identified, of which visual exposure was the most noteworthy. The DPOE model presented appears to be efficient but would nonetheless profit from being validated by other cases.

"I look at my own forest and fields in a different way": the lived experience of nature-based therapy in a therapy garden when suffering from stress-related illness.

Evidence confirms that nature-based therapy (NBT) has a positive effect on people with mental illnesses. However, there is a lack of evidence on the meaning of NBT for specific patient groups. The Nacadia® Therapy Garden was designed according to an evidence-based design process, and an NBT programme was developed. The aim of the study was to illuminate the phenomenon of participants' lived experience of the NBT in Nacadia. Fourteen participants took part in semi-structured interviews (SSIs), and by way of reflective lifeworld research, the SSIs were analysed to identify and describe the meanings of the phenomenon. The essence of the phenomenon was found to be a process of adopting a searching approach to NBT and Nacadia to become familiar with the conditions. This familiarity stimulated the development of confidentiality and attachment to Nacadia. Feeling protected, safe, cared for, and not exposed was important, and motivated feelings of freedom, reduced demands, and increased the ability to access and try a spectrum of NBT activities. It encouraged participants to develop personal approaches and coping strategies to implement in their everyday lives for moving on.

It is not all bad for the grey city - A crossover study on physiological and psychological restoration in a forest and an urban environment.

Today, urbanization presents a challenge to urban planning with regard to creating healthy living environments. The aim of this research is to gain further knowledge of the restorativeness of a best case urban and natural environment: that is a historic down town urban environment and forest environment located in an arboretum. The study has a cross-over design where 51 (N) female university students are exposed to the two environments through both seated viewing and walking. A mixed method approach is used with both physiological measurements of blood pressure (BP) and heart rate variability (HRV) and psychological measurements of mood change and perceived restorativeness. The HRV results show no significant differences between the two environments, and both environments are found to be more physiologically restorative than being at the office or on the minibus. The results of the psychological measures indicate that the forest walk has a positive effect on mood, while the walk in the urban environment has no effect. The forest environment is also rated more highly with regard to perceived restorativeness than the urban environment. The results support the current research that shows natural environments as more restorative than urban environments. The study also adds to the ongoing debate on healthy urban planning by indicating that architectural and historical qualities may be associated with the physiological well-being of citizens.

Corrigendum to "Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration".

[This corrects the article DOI: 10.1155/2016/2424306.].

'Everything just seems much more right in nature': How veterans with post-traumatic stress disorder experience nature-based activities in a forest therapy garden.

Available evidence shows that an increasing number of soldiers are seeking help for post-traumatic stress disorder. The post-traumatic stress disorder condition has big emotional and psychological consequences for the individual, his/her family and the society. Little research has been done to explore the impact of nature-based therapy for veterans with post-traumatic stress disorder although there is a growing amount of evidence pointing towards positive outcome. This qualitative study aims to achieve a deeper understanding of this relationship from the veteran's perspective. Eight Danish veterans participated in a 10-week nature-based therapy. Qualitative interviews were conducted and analysed using the interpretative phenomenological method. The results indicated that the veterans have achieved tools to use in stressful situations and experienced an improvement in their post-traumatic stress disorder symptoms.

Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration.

Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes.

Studies on the metabolism of tolmetin to the chemically reactive acyl-coenzyme A thioester intermediate in rats.

Carboxylic acids may be metabolized to acyl glucuronides and acyl-coenzyme A thioesters (acyl-CoAs), which are reactive metabolites capable of reacting with proteins in vivo. In this study, the metabolic activation of tolmetin (Tol) to reactive metabolites and the subsequent formation of Tol-protein adducts in the liver were studied in rats. Two hours after dose administration (100 mg/kg i.p.), tolmetin acyl-CoA (Tol-CoA) was identified by liquid chromatography-tandem mass spectrometry in liver homogenates. Similarly, the acyl-CoA-dependent metabolites tolmetin-taurine conjugate (Tol-Tau) and tolmetin-acyl carnitine ester (Tol-Car) were identified in rat livers. In a rat bile study (100 mg/kg i.p.), the S-acyl glutathione thioester conjugate was identified, providing further evidence of the formation of reactive metabolites such as Tol-CoA or Tol-acyl glucuronide (Tol-O-G), capable of acylating nucleophilic functional groups. Three rats were treated with clofibric acid (150 mg/kg/day i.p. for 7 days) before dose administration of Tol. This resulted in an increase in covalent binding to liver proteins from 0.9 nmol/g liver in control rats to 4.2 nmol/g liver in clofibric acid-treated rats. Similarly, levels of Tol-CoA increased from 0.6 nmol/g to 4.4 nmol/g liver after pretreatment with clofibric acid, whereas the formation of Tol-O-G and Tol-Tau was unaffected by clofibric acid treatment. However, Tol-Car levels increased from 0.08 to 0.64 nmol/g after clofibric acid treatment. Collectively, these results confirm that Tol-CoA is formed in vivo in the rat and that this metabolite can have important consequences in terms of covalent binding to liver proteins.

In vitro and in vivo studies on acyl-coenzyme A-dependent bioactivation of zomepirac in rats.

Zomepirac [ZP, 5-(chlorobenzoyl)-1,4-dimethylpyrrole-2-acetic acid] was withdrawn from the market because of unpredictable allergic reactions that may have been caused by ZP-protein adducts formed by reaction of the reactive acyl glucuronide of ZP (ZP-O-G) with endogenous proteins. To test the hypothesis that the reactive ZP acyl coenzyme A thioester (ZP-CoA) was formed and potentially could contribute to formation of ZP-protein adducts, we investigated the acyl CoA-dependent metabolism of ZP in freshly isolated rat hepatocytes (1 mM) and in vivo (100 mg ZP/kg, ip) in rat livers (2 h after dose administration), rat bile (0-4 h), and rat urine (0-24 h). ZP-CoA was detected in freshly isolated hepatocytes and in vivo in rat livers by LC/MS/MS. In addition, the ZP glycine conjugate (ZP-Gly) and ZP taurine conjugates (ZP-Tau) were identified by LC/MS/MS in rat hepatocytes and in vivo in rat livers, rat urine, and rat bile. The identities of ZP-CoA, ZP-Gly, and ZP-Tau were confirmed by comparison of retention times and MS/MS spectra with those of authentic standards. Moreover, the ZP acyl carnitine ester was detected in rat urine and rat bile based upon (i) the chlorine isotope pattern, (ii) MS/MS spectra showing significant ions characteristic for carnitine (m/z 60, 144 and loss of m/z 59) and ZP (m/z 139), and (iii) accurate mass measurements with a mass accuracy of 0.2 ppm. ZP-CoA serves as an obligatory intermediate in the formation of ZP-Gly, ZP-Tau, and ZP carnitine ester, and it is therefore of mechanistic significance that these conjugates were identified. Finally, time-dependent concentration profiles obtained in experiments with rat hepatocytes and in vivo from quantitative analysis of rat livers indicate that ZP-CoA, in addition to ZP-O-G, may contribute to formation of the potentially toxic covalent ZP-protein adducts.

In vitro reactivity of carboxylic acid-CoA thioesters with glutathione.

The chemical reactivity of acyl-CoA thioesters toward nucleophiles has been demonstrated in several recent studies. Thus, intracellularly formed acyl-CoAs of xenobiotic carboxylic acids may react covalently with endogenous proteins and potentially lead to adverse effects. The purpose of this study was to investigate whether a correlation could be found between the structure of acyl-CoA thioesters and their reactivities toward the tripeptide, glutathione (gamma-Glu-Cys-Gly). The acyl-CoA thioesters of eight carboxylic acids (ibuprofen, clofibric acid, indomethacin, fenbufen, tolmetin, salicylic acid, 2-phenoxypropionic acid, and (4-chloro-2-methyl-phenoxy)acetic acid (MCPA)) were synthesized, and each acyl-CoA (0.5 mM) was incubated with glutathione (5.0 mM) in 0.1 M potassium phosphate (pH 7.4, 37 degrees C). All of the acyl-CoAs reacted with glutathione to form the respective acyl-S-glutathione products, with MCPA-CoA having the highest rate of conjugate formation (120 +/- 10 microM/min) and ibuprofen-CoA having the lowest (1.0 +/- 0.1 microM/min). The relative reactivities of the acyl-CoAs were dependent on the substitution at the carbon atom alpha to the acyl carbon and on the presence of an oxygen atom in a position beta to the acyl carbon and were as follows: phenoxyacetic acid > o-hydroxybenzoic acid--phenoxypropionic acid > arylacetic acid derivatives > 2-methyl-2-phenoxypropionic acid--2-phenylpropionic acid. For each acyl-CoA thioester, the overall hydrolysis rate was determined as the time-dependent formation of parent compound. A linear trend was observed when comparing the reactivities of the acyl-CoAs with glutathione with the corresponding overall hydrolysis rates. Thus, the most reactive compound (MCPA-CoA) was also the compound with the highest rate of hydrolysis and the least reactive compounds (ibuprofen-CoA, clofibryl-CoA) were also the compounds least susceptible to hydrolysis.