Nature, health and climate.

The importance of nature for human health has received increasing attention in recent years and is at the focus of this review. Research has shown benefits for physical, mental, and social health as well as for the climate. Nature-based health interventions have already been partly implemented in social care and in the healthcare system. However, more research is needed to support the systematic development and evaluation of nature-based interventions. We need to identify which interventions are most effective for whom, with the goal of providing evidence-based, sustainable, and climate-friendly health improvements.

Understanding healthcare providers' experiences with video recording of patient consultations.

AIM: To understand healthcare providers' experiences with video recording of patient consultations. BACKGROUND: Video recordings have been recognised to be an effective method to evaluate in situ interactions in clinical practice. The video recordings are often conducted by researchers, but active involvement of healthcare providers into the process of recording is evolving. Still, little is known of how video recordings by healthcare providers may influence daily clinical practice and potentials for direct use to guide practice development. METHODS: A qualitative design was used, conducting two focus group interviews including 12 healthcare providers representing eight different healthcare services who provide municipal cardiac rehabilitation. Interpretive description was used as the methodological framework, and symbolic interactionism served as the theoretical lens. FINDINGS: Three themes were identified reflecting healthcare providers' experiences with video recording of patient consultations: 'Concerns of compromising primary work tasks', 'Exposing professional and personal skills' and 'A new learning dimension'. Overall, the three themes represent the process of video recording own practices attached to patient consultations and the personal investment attached to the video data. Also, how the recordings may provide new insights for practice development in terms of individual and team-based performance in patient consultations. CONCLUSION: Video recordings by healthcaref providers may be a useful source to provide information and learning about patient consultation practice to use in research and supervision, keeping in mind their challenges of implementation into daily clinical practice.

The potential of outdoor contexts within community-based rehabilitation to empower people with disabilities in their rehabilitation.

Purpose: The aim was to examine the potential of outdoor contexts within community-based rehabilitation to empower people with disabilities in their rehabilitation.Materials and methods: Interpretive description was applied as the methodology in a 5-month ethnographic fieldwork study, and guided by social practice theory. In total, 115 people with disabilities were included for participant observation, of which 15 participants were recruited for individual walking interviews.Results: Analysis revealed four overlapping themes. Firstly, "Revisiting the Outdoors" appeared to be an overarching theme, which created a basis for "Building Autonomy" among the participants. The varied outdoor experiences empowered the participants to take a more active role in their rehabilitation. These experiences afforded unique opportunities for "Connecting with Community" and, finally, "Embodied Learning" - that could be transferred to home and to other everyday contexts.Conclusion: Outdoor contexts within community-based rehabilitation appeared to hold strong potential for connecting people with disabilities to communities. Although barriers exist, we argue that revisiting the outdoors supports collective awareness and action with the capacity to influence community attitudes more broadly.IMPLICATIONS FOR REHABILITATIONOutdoor contexts within community-based rehabilitation for people with disabilities capitalise on the features of both indoor and outdoor environments with activities that meet shifting individual priorities and needs.Outdoor contexts within community-based rehabilitation offer people with disabilities empowering experiences that are part of the landscape of everyday life and transfer well to home and other environments.Community-based rehabilitation directly involving outdoor contexts and supported by professional skills provides a crucial bridge from individual rehabilitation to community belonging.

Physical health status in first-degree relatives of patients with bipolar disorder, a systematic review.

OBJECTIVE: This systematic literature search aimed to investigate the physical health status of first-degree relatives to patients with bipolar disorder. There is abundant evidence for familial aggregation of both bipolar disorders, cardiovascular and autoimmune diseases. However, a review gathering data on the physical health status in first-degree relatives to patients with bipolar disorder is missing. We hypothesized that first-degree relatives of bipolar probands would express higher rates of physical diseases and somatic morbidity. METHOD: We conducted a systematic literature search in three different databases PubMed, Embase and PsychInfo. The search identified 10 studies comparing 24,277 unaffected first-degree relatives with 318.933 controls persons. RESULTS: Seven out of 10 studies showed that first-degree relatives had statistically significantly higher rates of one or more physical diseases or increased morbidity, including cardiovascular diseases, infections, autoimmune thyroiditis, pernicious anaemia, and higher mortality compared with control persons. CONCLUSION: Findings from this systematic literature review did not unambiguously confirm a possible link between bipolar disorder and overall increased risk of physical diseases in first-degree relatives of probands with bipolar disorder. However, these results could suggest that first-degree relatives of probands with bipolar disorder could have a predisposition to poorer physical health than the general population and that this aspect warrants further investigation.

Indirect comparison of efficacy of dupilumab versus mepolizumab and omalizumab for severe type 2 asthma.

This indirect comparison of dupilumab, mepolizumab and omalizumab for patients with severe type 2 asthma fulfilling start-up criteria for more than one drug shows no significant efficacy differences https://bit.ly/3pK9Nf9.

"It Was Definitely an Eye-Opener to Me"-People with Disabilities' and Health Professionals' Perceptions on Combining Traditional Indoor Rehabilitation Practice with an Urban Green Rehabilitation Context.

Research points to the health benefits of rehabilitation in urban green spaces. Nevertheless, more studies indicate complexity of utilising urban green spaces in an established health system context. An understanding of challenges related to rehabilitation in urban green spaces remains unaddressed. Therefore, the aim was to describe and analyse people with disabilities' and health professionals' perceptions on combining traditional indoor rehabilitation practice with an urban green rehabilitation context. The interpretive description methodology was applied supplemented by Edgar Schein's Model of Organisational Culture. Three online focus group interviews were conducted with people with disabilities (n = 4) and health professionals (n = 10). Three interrelated themes formed an understanding of rehabilitation practice in an urban green rehabilitation context: "ambivalence due to contextual change", "negotiating rehabilitation assumptions" and "expanding the frame of rehabilitation". Expanding the frame of rehabilitation to an urban green context may provide a basis for enhancing compatibility to everyday life for people with disabilities and still accommodate structural quality standards of professional rehabilitation practice.

Navigating a Middle Ground - Exploring Health Professionals' Experiences and Perceptions of Providing Rehabilitation in Outdoor Community Settings.

Contemporary practice has started to rethink use of outdoor and community environments for advancing comprehensive rehabilitation outcomes. The aim is to examine health professionals' experiences and perceptions of providing rehabilitation in outdoor community settings. The purpose is to use these experiences to generate practice-based knowledge in using the outdoors as a means to guide community-based rehabilitation. The Interpretive Description methodology was accompanied by social practice theory. Fieldwork was conducted utilizing participant observation, photovoice, and focus-group interviews. Included were 27 health professionals. The analysis revealed how "naturalistic learning opportunities" offered health professionals strategies to empower activity and participation levels and yet invoked "rehabilitation setting tensions." A continuum was engaged in the theme "navigating a middle ground," representing an integrated environment approach; rehabilitation in conventional indoor and outdoor community settings. Development of a sustainable concept for outdoor community-based rehabilitation involves strengthening health professionals' competencies and skills for providing outdoor and community work.

Efficacy of omalizumab in children, adolescents, and adults with severe allergic asthma: a systematic review, meta-analysis, and call for new trials using current guidelines for assessment of severe asthma.

BACKGROUND: Omalizumab is approved for treating severe allergic asthma from age 6, but the definition of severe asthma including a systematic assessment to rule out difficult-to-treat asthma has changed since the drug was approved in 2003. METHODS: We conducted a systematic review and meta-analysis of two critical (exacerbation rate, oral corticosteroid (OCS) treatment) and eight important clinical outcomes in children, adolescents and adults, and specifically searched papers for systematic assessment of severe asthma. RESULTS: Adults: seven studies (n = 2159) ascertaining exacerbation rate showing a 37% (95% CI 21-50) reduction in favor of omalizumab, larger than the pre-specified minimal clinically important difference (MCID) of 25%. Only one open-label study (n = 82) was identified assessing the percentage of patients experiencing reduction of OCS-maintenance treatment showing a significantly greater decrease in the omalizumab group (- 45% vs. + 18.3%, p = 0.002). Children and adolescents: four studies (n = 1551) reported data on exacerbations (no meta-analysis conducted), showed overall improvements in exacerbation rate and some passed MCID. No OCS studies were identified. No included studies provided systematic assessment of severe asthma according to current guidelines. CONCLUSIONS: Omalizumab provides clinically relevant improvements in exacerbation rate among children, adolescents, and adults and in OCS-reduction among adults. New studies incorporating a guideline-approached definition of severe asthma are warranted.

Experiences with and perspectives on goal setting in spinal cord injury rehabilitation: a systematic review of qualitative studies.

STUDY DESIGN: Systematic review of qualitative studies. OBJECTIVE: To synthesise qualitative research exploring the experiences and perspectives of persons with spinal cord injury (SCI), relatives and health professionals concerning goal setting in SCI rehabilitation. METHODS: Five electronic databases were searched. A search strategy was constructed with key concepts identified using PICo (Population, phenomena of Interest and Context). Peer reviewed studies complying with the inclusion criteria were selected. Interpretive Description methodology guided analysis and synthesis of the findings. RESULTS: The search yielded 427 records. Of 12 full text studies assessed for eligibility, four were included describing goal setting in SCI rehabilitation from the perspective of persons with SCI and health professionals. Persons with SCI described a need for goal setting to be related to their everyday life, whereas the health professionals tended to use the hospital setting as their point of reference. Persons with SCI emphasised the importance of being self-directed and taking an active role in goal setting and rehabilitation. No studies presented the perspective of relatives. CONCLUSIONS: This review illuminates the divergence in the understanding of goal setting between persons with SCI and health professionals. Goal setting in SCI rehabilitation often directly reflects physical functioning goals set by the health professionals, which does not prepare persons with SCI for everyday life and emotional issues. There is lack of focus on goals addressing psychosocial components such as family issues and change of roles. A shared process with goal setting relevant to persons with SCI and their everyday life is needed.

"Understanding my ALS". Experiences and reflections of persons with amyotrophic lateral sclerosis and relatives on participation in peer group rehabilitation.

PURPOSE: The aim of this study was to gain insight into experiences and reflections of persons with amyotrophic lateral sclerosis and relatives concerning the peer group rehabilitation programme "More Life - Less Illness". METHODS: This qualitative study used the Interpretive Description methodology with Symbolic Interactionism as the analytical framework. Eighteen programme participants representing persons with amyotrophic lateral sclerosis (n = 8) and relatives (n = 10) were included. Data consisted of individual interviews and participant observation. RESULTS: The analysis revealed two categorical themes, "Sense of Community Building" and "Understanding my ALS", which represented the participants' experiences and reflections on peer group rehabilitation. Through the analysis, it became apparent that "Sense of Community Building" gave rise to an increased and personalised understanding of amyotrophic lateral sclerosis among the participants. As a part of the continuous processing of the knowledge gained, "Facing Facts" and "Retaining Normality" appeared as subthemes regarding the participants' ability to live a less dependent and more meaningful life. CONCLUSIONS: This study of peer group rehabilitation for persons with amyotrophic lateral sclerosis and relatives indicates that programme participation leads to positive experiences in terms of living a shared meaningful life despite severe disability. The findings may guide practice to develop longitudinal peer group rehabilitation programmes with joint inclusion of persons with amyotrophic lateral sclerosis and relatives. Implications for Rehabilitation Peer group rehabilitation may facilitate an increased and personalised understanding of what it means to live with amyotrophic lateral sclerosis. A programme design with six months of sequential sessions enables a continuous processing of shared experiences and gained knowledge. Joint participation of persons with amyotrophic lateral sclerosis and their relatives supports both their internal relationship and social networking. Peer group rehabilitation in amyotrophic lateral sclerosis should help overcome obstacles concerning the needs of participants, accessibility, and geographical distance.

Pursuing Normality: Reflections on Cancer Survivorship Care of Lymphoma Survivors.

BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study was to understand the reflections on cancer survivorship care of lymphoma survivors to aid the future planning of cancer survivorship care and overcome barriers to participation. METHODS: Data were generated in a hematological ward during 4 months of ethnographic fieldwork, including participant observation and 46 semistructured interviews with 9 lymphoma survivors. Interpretive description methodology and social practice theory guided the analytical framework. RESULTS: "Pursuing normality" was an overall finding and was comprised of 2 overarching patterns, "future prospects" and "survivorship care perceptions," both implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease." CONCLUSION: The findings add to our understanding of possible barriers for participation in cancer survivorship care and outline important aspects to account for in the practice of health professionals. IMPLICATIONS FOR PRACTICE: The study findings may guide practice to establish a systematic approach for providing information to cancer survivors regarding the possible management of their symptoms and of the content and purpose of cancer survivorship care.

Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma - a systematic review and meta-analysis.

Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to -0.94 annual exacerbations (95% CI -1.08;-0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

Positive allosteric modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action.

Drugs that increase monoamine neurotransmission are effective in both anxiety and depression. The therapeutic effects of monoamine-based antidepressant drugs may involve indirect effects on neurotransmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR). Thus, chronic antidepressant treatment increases AMPAR-mediated neurotransmission and AMPAR-positive allosteric modulators have shown antidepressant-like efficacy in rodents. Here, the effect of enhanced AMPAR neurotransmission on the antidepressant-like and anxiolytic-like actions of the selective serotonin reuptake inhibitor citalopram (0-10 mg/kg) was investigated in mice using the AMPAR-positive allosteric modulator LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed using the forced-swim test (FST), whereas anxiolytic-like effects were tested using the elevated zero maze (EZM) and the marble burying test. LY451646 (3 mg/kg) increased swim distance in the FST and a subactive dose of LY451646 (1 mg/kg) enhanced the effect of citalopram in the FST. In the EZM, LY451646 (3 mg/kg) did not show anxiogenic effects alone, but blocked the anxiolytic-like action of citalopram in the EZM, as reflected by an increase in the latency to enter the open areas and a decrease in the number of entries and time spent in the open areas in citalopram-treated mice. In the marble burying test, LY451646 (3 mg/kg) showed no effect alone, but significantly attenuated the anxiolytic-like effect of citalopram (1.25-2.5 mg/kg) by increasing the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have ramifications in the search for AMPAR-based novel anxiolytic and antidepressant treatments.

[Acute aortic syndrome].

Acute aortic syndrome is a group of pathogenic conditions including aortic dissection, intramural haematoma, penetrating ulcer and aortic aneurysm. The syndrome is a challenging clinical diagnosis because the symptoms are numerous and diverse with similarity to other more common conditions. Delayed diagnosis and treatment can be fatal. Computed tomography angiography is the most important diagnostic tool and is the first choice when acute aortic syndrome is suspected. With this article, we wish to raise awareness of the incidence of acute aortic syndrome and the clinical features of the syndrome.

Human ASPL/TUG interacts with p97 and complements the proteasome mislocalization of a yeast ubx4 mutant, but not the ER-associated degradation defect.

BACKGROUND: In mammalian cells, ASPL is involved in insulin-stimulated redistribution of the glucose transporter GLUT4 and assembly of the Golgi apparatus. Its putative yeast orthologue, Ubx4, is important for proteasome localization, endoplasmic reticulum-associated protein degradation (ERAD), and UV-induced degradation of RNA polymerase. RESULTS: Here, we show that ASPL is a cofactor of the hexameric ATPase complex, known as p97 or VCP in mammals and Cdc48 in yeast. In addition, ASPL interacts in vitro with NSF, another hexameric ATPase complex. ASPL localizes to the ER membrane. The central area in ASPL, containing both a SHP box and a UBX domain, is required for binding to the p97 N-domain. Knock-down of ASPL does not impair degradation of misfolded secretory proteins via the ERAD pathway. Deletion of UBX4 in yeast causes cycloheximide sensitivity, while ubx4 cdc48-3 double mutations cause proteasome mislocalization. ASPL alleviates these defects, but not the impaired ERAD. CONCLUSIONS: In conclusion, ASPL and Ubx4 are homologous proteins with only partially overlapping functions. Both interact with p97/Cdc48, but while Ubx4 is important for ERAD, ASPL appears not to share this function.

Vitellogenin as biomarker for estrogenicity in flounder Platichthys flesus in the field and exposed to 17α-ethinylestradiol via food and water in the laboratory.

The ability of 17α-ethinylestradiol (EE2) to elevate vitellogenin levels were investigated in male flounder Platichthys flesus and vitellogenin concentrations in flounders from the Danish coastal environment were determined. Male flounders were exposed to 17α-ethinylestradiol (EE2) via food or water. Average vitellogenin concentrations in the control fish ranged between 25 and 100 ng mL(-)(1). Exposure to 5.1, 8.1 and 16.8 ng EE2 L(-)(1) in water and 500 and 5000 ng EE2 kg(-)(1) body weight (bw) every second day in the food increased the plasma vitellogenin concentration in a concentration and time dependent manner, whereas exposure to 2.7 ng EE2 L(-)(1) in water for 21 d and 5 and 50 ng EE2 kg(-)(1) bw for 12 days in the food did not. EE2 could be detected in liver and testes (but not in muscle) after exposure to 8.1 and 16.8 ng EE2 L(-)(1) in the water and 5000 ng EE2 kg(-)(1) bw in the food; the highest concentration was 6 ng g(-)(1) wet weight in liver. The majority of the male flounders collected from nine coastal Danish sites from 1999 to 2004 had vitellogenin concentrations below 100 ng mL(-)(1), and only at two sites moderate estrogenic inputs were indicated.

The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.

The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

New ATPase regulators--p97 goes to the PUB.

The conserved eukaryotic AAA-type ATPase complex, known as p97 or VCP in mammals and Cdc48 in yeast, is involved in a number of cellular pathways, including fusion of homotypic membranes, protein degradation, and activation of membrane-bound transcription factors. Most likely, p97 is directed to this broad spectrum of cellular functions through its binding to specific cofactors. More than 20 different p97 cofactors have been described to date and our understanding of their cellular functions is rapidly expanding. Common to these proteins is their intimate connection with the ubiquitin system. Recently, a small, conserved family of proteins, containing PUB domains, was found to function as p97 adaptors. Intriguingly, their association with p97 is regulated by tyrosine phosphorylation, suggesting that they act as a relay between signalling pathways and p97 functions. Here we give an overview of the currently known PUB-domain proteins and other p97-interacting proteins.

Thioredoxin Txnl1/TRP32 is a redox-active cofactor of the 26 S proteasome.

The 26 S proteasome is a large proteolytic machine, which degrades most intracellular proteins. We found that thioredoxin, Txnl1/TRP32, binds to Rpn11, a subunit of the regulatory complex of the human 26 S proteasome. Txnl1 is abundant, metabolically stable, and widely expressed and is present in the cytoplasm and nucleus. Txnl1 has thioredoxin activity with a redox potential of about -250 mV. Mutant Txnl1 with one active site cysteine replaced by serine formed disulfide bonds to eEF1A1, a substrate-recruiting factor of the 26 S proteasome. eEF1A1 is therefore a likely physiological substrate. In response to knockdown of Txnl1, ubiquitin-protein conjugates were moderately stabilized. Hence, Txnl1 is the first example of a direct connection between protein reduction and proteolysis, two major intracellular protein quality control mechanisms.