Epistemological aspects of participatory design studies conducted in the field of health science.

AIM(S): To discuss the methodological aspects of participatory design, arguing for a three-phase approach and the suitability of situating participatory design within a phenomenological-hermeneutical tradition in health science. DESIGN AND METHODS: Methodological discussion based on participatory design theory, epistemology and research studies. RESULTS: The epistemological and methodological discussions show how the core values and key elements of participatory design align with the phenomenological-hermeneutical approach. In addition, examples of participatory design studies are provided to illustrate how it can be conducted in health science. CONCLUSION: Participatory design is a flexible framework based on genuine participation, defined by three core values: having a say, mutual learning and democratization. The iterative processes allow for adjustments in alignment with the core values and the scientific stance that defines the choice of methods, tools and techniques. A phenomenological-hermeneutic approach in participatory design studies is relevant and aligned with the core values of participatory design. Thus, this paper argues for a close integration between the participatory design methodology and the phenomenological-hermeneutic scientific approach within health science. IMPLICATIONS FOR THE PROFESSION: Participatory design is a powerful methodology with core values that can co-design sustainable health technologies with potential to impact patient care and the clinical practice of nurses. When combined with qualitative research methods, patients' lived experiences serve as the foundation for improving clinical nursing practice. Discussing the epistemological aspects of participatory design provides nurse researchers with a coherent methodological understanding, essential for the continual development of nursing research. IMPACT: This paper discusses the research methodology of participatory design within health sciences. It aims to address the lack of understanding of the methodology, particularly within a specific scientific stance. The main finding is the elaboration on participatory design and the relevance of a phenomenological-hermeneutical approach. The paper has the potential to impact researchers, master's and PhD students, as well as others engaged in participatory design or other methodologies related to user involvement within health science. REPORTING METHOD: No available EQUATOR guidelines were applicable to this methodological paper, as no new data were created or analysed. PATIENT OR PUBLIC CONTRIBUTION: There was no direct patient or public contribution, as this is a methodological paper.

"I am just trying to live a life!" -a qualitative study of the lived experience of pressure ulcers in people with spinal cord injuries.

BACKGROUND: Pressure ulcers (PUs) are frequently reported in people with spinal cord injuries (SCI). Wound management in people with SCI involves relieving pressure on the affected area by means of immobilisation and bed rest. The healing time of a PU can vary, but often takes several months or even years, causing people to stay in bed for prolonged periods of time. OBJECTIVE: This study aims to explore the perspectives and lived experiences of people with SCI who are affected by PUs. DESIGN: and method: This study is a qualitative explorative study that employs individual semi-structured in-depth interviews to obtain the narratives of people with SCI and a pressure ulcer. We used a phenomenological-hermeneutic approach that was inspired by Ricoeur's theory of interpretation. The analysis was performed in three levels: Naïve reading, structural analysis and critical interpretation and discussion. PARTICIPANTS: and setting: Ten people with SCI who were being treated in the Danish healthcare system for their PU participated in this study: six participants had experienced a complete traumatic SCI, three had an incomplete traumatic SCI, and one had a non-traumatic complete SCI. The study included nine men and one woman, aged 49-81 years (mean 64). Nine had a PU in the seating area, while one had the ulcer on the leg. RESULTS: The analysis revealed three themes: 1. Struggling to balance prevention with an active, meaningful life, 2. Challenges and consequences of pressure relief protocols and bed rest, 3. Experiencing prolonged and incoherent treatment with varying levels of staff engagement and competencies. CONCLUSIONS: People with SCI and a PU have difficulty balancing their active, redefined lives when subjected to a strict pressure relief protocol. The consequences of immobility caused by pressure relief include reduced social and community participation and decreased quality of life. PU treatment is experienced as incoherent and unnecessarily lengthy, leading to a deterioration in the wounds. Improving PU treatment for people with SCI is of utmost importance and has the potential to benefit not only the people with SCI but also the healthcare system and the economy.

Should oral care be about more than a gut feeling? A qualitative study investigating patients' and healthcare professionals' experiences.

AIM: To explore patients' and healthcare professionals' (HCPs) experiences of oral care during hospitalisation to identify needs and challenges. BACKGROUND: Daily oral care is important to patients' health and well-being, to prevent diseases in the oral cavity, systemic infections and increased morbidity, which subsequently can lead to prolonged hospitalisation and, at worst, increased mortality. Despite this knowledge, oral care is a neglected part of nursing practice. Studies do not clearly identify barriers regarding oral care, as the existing knowledge is inadequate. DESIGN: A qualitative study exploring participants' experiences to gain new in-depth knowledge of oral care among hospitalised patients. METHODS: A phenomenological-hermeneutic approach was applied. Participant observations were conducted on five hospital wards, combined with individual semi-structured interviews with 16 patients and 15 HCP. Data analysis was based on Ricoeur's theory of narrative and interpretation. RESULTS: Four themes describing the challenges regarding oral care emerged: Oral care as a gut feeling; oral care fades into the background; even self-reliant patients need help with oral care; and the mouth reflects the life lived. CONCLUSIONS: The identified challenges show there is a need for improvement in the health professional approach to oral care in nursing practice. Focus on increasing HCPs' knowledge, skills and competences can increase their nursing agency and support patients' self-care capacity. IMPACT: Investigation of oral care during hospitalisation revealed four main challenges concerning both patients' and HCPs' lack of knowledge and awareness of oral care. Thus, patients and HCPs should be included in developing solutions to improve oral care in nursing practice. REPORTING METHODS: The COREQ criteria for reporting qualitative research were adhered to. PATIENT CONTRIBUTION: A patient representative was involved in the discussion of the proposal, conduct and results of the study.

SARS-CoV-2 epidemiology, antibody dynamics, and neutralisation capacity in Irish healthcare workers in the era of booster COVID-19 vaccinations.

Background: The PRECISE Study, a multi-phase cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers (HCW) investigated: (1) risk factors for SARS-CoV-2 seropositivity, (2) the durability of antibody responses in a highly vaccinated HCW cohort, and (3) the neutralisation capacity of detected antibodies, prior to booster COVID-19 vaccination. Materials and methods: Serology samples were collected across two hospital sites in November 2021 and analysed using the Roche Elecsys Anti-SARS-CoV-2/Elecsys-S Anti-SARS-CoV-2 assays to detect anti-nucleocapsid (N) and anti-spike (S) antibodies respectively. Paired serology results from prior study phases were used to analyse changes in individual HCW serostatus over time. Risk-factors for SARS-CoV-2 infection were assessed for demographic and work-related factors. Antibody neutralisation capacity was assessed in a subset of samples via an in vitro ACE2 binding enzyme-linked immunosorbent assay. Results: 2,344 HCW samples were analysed. Median age was 43 years (IQR 33-50) with 80.5% (n = 1,886) female participants. Irish (78.9%, n = 1,850) and Asian (12.3%, n = 288) were the most commonly reported ethnicities. Nursing/midwifery (39.3%, n = 922) was the most common job role. 97.7% of participants were fully vaccinated, with Pfizer (81.1%, n = 1,902) and AstraZeneca (16.1%, n = 377) the most common vaccines received. Seroprevalence for anti-SARS-CoV-2 antibodies indicating prior infection was 23.4%, of these 33.6% represented previously undiagnosed infections. All vaccinated participants demonstrated positive anti-S antibodies and in those with paired serology, no individual demonstrated loss of previously positive anti-S status below assay threshold for positivity. Interval loss of anti-N antibody positivity was demonstrated in 8.8% of previously positive participants with paired results. Risk factors for SARS-CoV-2 seropositivity suggestive of previous infection included age 18-29 years (aRR 1.50, 95% CI 1.19-1.90, p < 0.001), India as country of birth (aRR 1.35, 95% CI 1.01-1.73, p = 0.036), lower education level (aRR 1.35, 95% CI 1.11-1.66, p = 0.004) and HCA job role (aRR 2.12, 95% CI 1.51-2.95, p < 0.001). Antibody neutralisation varied significantly by anti-SARS-CoV-2 antibody status, with highest levels noted in those anti-N positive, in particular those with vaccination plus previous SARS-CoV-2 infection. Conclusion: All vaccinated HCWs maintained anti-S positivity prior to COVID-19 booster vaccination, however anti-N positivity was more dynamic over time. Antibody neutralisation capacity was highest in participants with COVID-19 vaccination plus prior SARS-CoV-2 infection.

Investigation of an international outbreak of multidrug-resistant monophasic Salmonella Typhimurium associated with chocolate products, EU/EEA and United Kingdom, February to April 2022.

An extensive multi-country outbreak of multidrug-resistant monophasic Salmonella Typhimurium infection in 10 countries with 150 reported cases, predominantly affecting young children, has been linked to chocolate products produced by a large multinational company. Extensive withdrawals and recalls of multiple product lines have been undertaken. With Easter approaching, widespread product distribution and the vulnerability of the affected population, early and effective real-time sharing of microbiological and epidemiological information has been of critical importance in effectively managing this serious food-borne incident.

Pregnenolone-methyl-ether enhances CLIP170 and microtubule functions improving spine maturation and hippocampal deficits related to CDKL5 deficiency.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a neurodevelopmental disease characterized by severe infantile seizures and intellectual disability. The absence of CDKL5 in mice causes defective spine maturation that can at least partially explain the cognitive impairment in CDKL5 patients and CDD mouse models. The molecular basis for such defect may depend on the capacity of CDKL5 to regulate microtubule (MT) dynamics through its association with the MT-plus end tracking protein CLIP170 (cytoplasmic linker protein 170). Indeed, we here demonstrate that the absence of CDKL5 causes CLIP170 to be mainly in a closed inactive conformation that impedes its binding to MTs. Previously, the synthetic pregnenolone analogue, pregnenolone-methyl-ether (PME), was found to have a positive effect on CDKL5-related cellular and neuronal defects in vitro. Here, we show that PME induces the open active conformation of CLIP170 and promotes the entry of MTs into dendritic spines in vitro. Furthermore, the administration of PME to symptomatic Cdkl5-knock-out mice improved hippocampal-dependent behavior and restored spine maturation and the localization of MT-related proteins in the synaptic compartment. The positive effect on cognitive deficits persisted for 1 week after treatment withdrawal. Altogether, our results suggest that CDKL5 regulates spine maturation and cognitive processes through its control of CLIP170 and MT dynamics, which may represent a novel target for the development of disease-modifying therapies.

Superficial Parotidectomy: Impact of Postoperative Drainage.

BACKGROUND: Use of suction drain after superficial parotidectomy (SP) is based on national consensus considered best practice, but there is no evidence on the effect of the treatment. The aim of the present study is to evaluate the effectiveness of drainage after SP by evaluating the rate of complications after SP in relation to the (ie, duration) of drainage and tumor size. METHODS: Retrospective analysis was performed involving data from all consecutive patients undergoing SP at the Ear, Nose, and Throat department, Regional Hospital West Jutland, Denmark, between January 1, 2011, and December 31, 2017. Demographics including comorbidity, medication, tumor size, postoperative secretion through the drainage, as well as complications (hematoma, seroma, infection, fistulas, Frey syndrome, facial nerve palsy) were registered. Patients with secretion below 25 mL were compared to patients with secretion above 25 mL, that is, drainage less than 24 hours versus longer than 24 hours. Results: Two hundred five consecutive patients undergoing SP were enrolled. The overall risk of postoperative infection was 16.2%. Ten of 33 patients with infection were also diagnosed with an hematoma or seroma. The risk of infection increased with secretion above 25 mL (27.2%) compared to patients with less than 25 mL (13.1%; P = .0318). The same accounts for the risk of seromas/hematomas (P = .0055). We found no evidence that demographics or comorbidity correlated to the secretion in the drainage, but there is a tendency toward male gender having a higher risk off secretion above 25 mL (odds ratio 1.39). CONCLUSION: Overall, the risk of complications after SP increased with secretion beyond 25 mL (ie, drainage for more than 24 hours). This applied in particular to infections and seromas/hematomas demanding treatment. The use of routine drainage after SP is questionable, and a randomized trial is warranted to unravel the necessity of postoperative drainage.

Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting.

Pregnenolone methyl-ether (PME) is a synthetic derivative of the endogenous neuroactive steroid pregnenolone (PREG), which is an important modulator of several brain functions. In addition to being the precursor of steroids, PREG acts directly on various targets including microtubules (MTs), the functioning of which is fundamental for the development and homeostasis of nervous system. The coordination of MT dynamics is supported by a plethora of MT-associated proteins (MAPs) and by a specific MT code that is defined by the post-translational modifications of tubulin. Defects associated with MAPs or tubulin post-translational modifications are linked to different neurological pathologies including mood and neurodevelopmental disorders. In this review, we describe the beneficial effect of PME in major depressive disorders (MDDs) and in CDKL5 deficiency disorder (CDD), two pathologies that are joint by defective MT dynamics. Growing evidence indeed suggests that PME, as well as PREG, is able to positively affect the MT-binding of MAP2 and the plus-end tracking protein CLIP170 that are both found to be deregulated in the above mentioned pathologies. Furthermore, PME influences the state of MT acetylation, the deregulation of which is often associated with neurological abnormalities including MDDs. By contrast to PREG, PME is not metabolised into other downstream molecules with specific biological properties, an aspect that makes this compound more suitable for therapeutic strategies. Thus, through the analysis of MDDs and CDD, this work focuses attention on the possible use of PME for neuronal pathologies associated with MT defects.

Loss of CDKL5 Causes Synaptic GABAergic Defects That Can Be Restored with the Neuroactive Steroid Pregnenolone-Methyl-Ether.

CDKL5 deficiency disorder (CDD) is an X-linked neurodevelopmental disorder characterised by early-onset drug-resistant epilepsy and impaired cognitive and motor skills. CDD is caused by mutations in cyclin-dependent kinase-like 5 (CDKL5), which plays a well-known role in regulating excitatory neurotransmission, while its effect on neuronal inhibition has been poorly investigated. We explored the potential role of CDKL5 in the inhibitory compartment in Cdkl5-KO male mice and primary hippocampal neurons and found that CDKL5 interacts with gephyrin and collybistin, two crucial organisers of the inhibitory postsynaptic sites. Through molecular and electrophysiological approaches, we demonstrated that CDKL5 loss causes a reduced number of gephyrin puncta and surface exposed γ2 subunit-containing GABAA receptors, impacting the frequency of miniature inhibitory postsynaptic currents, which we ascribe to a postsynaptic function of CDKL5. In line with previous data showing that CDKL5 loss impacts microtubule (MT) dynamics, we showed that treatment with pregnenolone-methyl-ether (PME), which promotes MT dynamics, rescues the above defects. The impact of CDKL5 deficiency on inhibitory neurotransmission might explain the presence of drug-resistant epilepsy and cognitive defects in CDD patients. Moreover, our results may pave the way for drug-based therapies that could bypass the need for CDKL5 and provide effective therapeutic strategies for CDD patients.

MECP2 mutations affect ciliogenesis: a novel perspective for Rett syndrome and related disorders.

Mutations in MECP2 cause several neurological disorders of which Rett syndrome (RTT) represents the best-defined condition. Although mainly working as a transcriptional repressor, MeCP2 is a multifunctional protein revealing several activities, the involvement of which in RTT remains obscure. Besides being mainly localized in the nucleus, MeCP2 associates with the centrosome, an organelle from which primary cilia originate. Primary cilia function as "sensory antennae" protruding from most cells, and a link between primary cilia and mental illness has recently been reported. We herein demonstrate that MeCP2 deficiency affects ciliogenesis in cultured cells, including neurons and RTT fibroblasts, and in the mouse brain. Consequently, the cilium-related Sonic Hedgehog pathway, which is essential for brain development and functioning, is impaired. Microtubule instability participates in these phenotypes that can be rescued by HDAC6 inhibition together with the recovery of RTT-related neuronal defects. Our data indicate defects of primary cilium as a novel pathogenic mechanism that by contributing to the clinical features of RTT might impact on proper cerebellum/brain development and functioning, thus providing a novel therapeutic target.

Nutrient Restriction has Limited Short-Term Effects on Gut, Immunity, and Brain Development in Preterm Pigs.

BACKGROUND: Extrauterine growth restriction (EUGR) in preterm infants is associated with higher morbidity and impaired neurodevelopment. Early nutrition support may prevent EUGR in preterm infants, but it is not known if this improves organ development and brain function in the short and long term. OBJECTIVE: Using pigs as models for infants, we hypothesized that diet-induced EUGR impairs gut, immunity, and brain development in preterm neonates during the first weeks after birth. METHODS: Forty-four preterm caesarean-delivered pigs (Danish Landrace × Large White × Duroc, birth weight 975 ± 235 g, male:female ratio 23:21) from 2 sows were fed increasing volumes [32-180 mL/(kg·d)] of dilute bovine milk (EUGR group) or the same diet fortified with powdered bovine colostrum for 19 d (CONT group, 50-100% higher protein and energy intake than the EUGR group). RESULTS: The EUGR pigs showed reduced body growth (-39%, P < 0.01), lower plasma albumin, phosphate, and creatine kinase concentrations (-35 to 14%, P < 0.05), increased cortisol and free iron concentrations (+130 to 700%, P < 0.05), and reduced relative weights of the intestine, liver, and spleen (-38 to 19%, all P < 0.05). The effects of EUGR on gut structure, function, microbiota, and systemic immunity were marginal, although EUGR temporarily increased type 1 helper T cell (Th1) activity (e.g. more blood T cells and higher Th1-related cytokine concentrations on day 8) and reduced colon nutrient fermentation (lower SCFA concentration; -45%, P < 0.01). Further, EUGR pigs showed increased relative brain weights (+19%, P < 0.01), however, memory and learning, as tested in a spatial T-maze, were not affected. CONCLUSION: Most of the measured organ growth, and digestive, immune, and brain functions showed limited effects of diet-induced EUGR in preterm pigs during the first weeks after birth. Likewise, preterm infants may show remarkable physiological adaptation to deficient nutrient supply during the first weeks of life although early life malnutrition may exert negative consequences later.

Alpha-Lactalbumin Enriched Whey Protein Concentrate to Improve Gut, Immunity and Brain Development in Preterm Pigs.

Human milk is rich in nutritional factors, such as alpha-lactalbumin (α-Lac), and important for neonatal development, but nutrient supplementation may be required for optimal growth. Using a pig model, we hypothesized that α-Lac-enriched whey protein concentrate (WPC) supplementation improves neonatal development. Cesarean-delivered preterm pigs were fed either dilute bovine milk (REF) or REF milk supplemented with WPC with normal (STANDARD-ALPHA) or high (HIGH-ALPHA) α-Lac. Clinical, gut, immune and cognitive endpoints (open field, T-maze) were assessed and tissues collected at Day 19. The growth of STANDARD-ALPHA and HIGH-ALPHA were higher than REF (31 vs. 19 g/kg/d). Most organ weights, gut, immunity and brain variables were similar between WPC groups. HIGH-ALPHA had a higher bone mineral content, colon microbial diversity and an abundance of specific bacteria and microbial metabolites, and tended to show a faster food transit time (p = 0.07). Relative to REF, WPC pigs showed higher relative organ weights, blood amino acids, blood neutrophil function, and microbial metabolites, but lower brush-border enzyme activities and plasma cortisol. Cognition outcomes did not differ among the groups. In conclusion, WPC supplementation of milk improved some growth, gut and immunity parameters in preterm pigs. However, increasing the α-Lac content beyond human milk levels had limited effects on the immature gut and developing brain.

Evaluation of a telehealth solution developed to improve follow-up after kidney Transplantation.

AIM: To explore patients' and healthcare professionals' experiences of using a telehealth solution developed to improve follow-up after kidney transplantation. BACKGROUND: Transplantation is the treatment of choice whenever feasible for patients with end-stage kidney disease. However, it implies lifelong adherence of self-monitoring, medicine and other restrictions to ensure successful outcomes. Based on user involvement, a telehealth solution was developed to support patients and healthcare professionals post-transplantation. DESIGN: An explorative qualitative study with a phenomenological-hermeneutic approach. METHODS: The developed app and workflow for follow-up were tested by patients and healthcare professionals and evaluated with interviews. In total, 16 patients and 20 healthcare professionals participated. Individual interviews were conducted with the patients, four nurses participated in two sets of interviews, and 16 doctors participated in a focus group. Data were analysed with inspiration from Ricoeur's theory of interpretation, on three levels: Naïve reading, structural analysis and critical interpretation and discussion. The COREQ checklist was applied in reporting the study. RESULTS: Three themes emerged: Challenging conditions for training sessions, telehealth improves patient reflection and collaboration, and telehealth gives patients a voice in consultations. In a challenging time, post-transplantation patients found the app easy to use; it facilitated support and reflection on how to manage. It also supported both patients and healthcare professionals at follow-up consultations in terms of enhanced preparation, improved dialogue and enabling consultations by phone. CONCLUSION: The study showed that patients and healthcare professionals found the app and workflow valuable and easy to use. The Patient Data feature in the app has potential as a communication tool. However, adjustments and further investigations are needed to develop the solution. RELEVANCE TO CLINICAL PRACTICE: The potential of telehealth brings new opportunities to provide treatment and care to newly transplanted patients. Telehealth can support both patients and health professionals by improving dialogue and collaboration.

User involvement in the development of a telehealth solution to improve the kidney transplantation process: A participatory design study.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease, and leads to everyday self-management of this chronic condition. This article aims to provide documentation for a participatory design study of a telehealth solution to improve the kidney transplantation process, and to identify the impact from the different participants in the participatory design study. Through a participatory design approach, a smartphone application (app) was developed for the entire kidney transplantation process together with a workflow for post-transplantation follow-up. A core element in participatory design is user involvement. By way of workshops and laboratory tests, the telehealth solution was developed in close cooperation with patients, their families, healthcare professionals, kidney association representatives, and Information Technology designers. The participatory design approach means that the telehealth solution was designed to be functional in a clinical setting, address patients' needs, and support their self-management.

'The hospital and everyday life are two worlds': Patients' and healthcare professionals' experiences and perspectives on collaboration in the kidney transplantation process.

AIM: To explore patients' and healthcare professionals' experiences and perspectives on collaboration in the kidney transplantation process. DESIGN: A qualitative study with a phenomenological-hermeneutic approach. METHOD: Participant observation and interviews were conducted with 18 patients, together with a focus group with eight healthcare professionals from April 2016-January 2017. The data analysis was inspired by Ricoeur's theory. RESULTS: While patients acknowledged that the healthcare professionals were experts, they also requested an everyday life approach to treatment and care, because both professional knowledge and everyday life experiences were needed to manage everyday life. A contrast between patients' experiences and healthcare professionals' knowledge was identified, and the empowerment approach could be a way to combine the different perspectives.

Microtubules: A Key to Understand and Correct Neuronal Defects in CDKL5 Deficiency Disorder?

CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental encephalopathy caused by mutations in the X-linked CDKL5 gene that encodes a serine/threonine kinase. CDD is characterised by the early onset of seizures and impaired cognitive and motor skills. Loss of CDKL5 in vitro and in vivo affects neuronal morphology at early and late stages of maturation, suggesting a link between CDKL5 and the neuronal cytoskeleton. Recently, various microtubule (MT)-binding proteins have been identified as interactors of CDKL5, indicating that its roles converge on regulating MT functioning. MTs are dynamic structures that are important for neuronal morphology, migration and polarity. The delicate control of MT dynamics is fundamental for proper neuronal functions, as evidenced by the fact that aberrant MT dynamics are involved in various neurological disorders. In this review, we highlight the link between CDKL5 and MTs, discussing how CDKL5 deficiency may lead to deranged neuronal functions through aberrant MT dynamics. Finally, we discuss whether the regulation of MT dynamics through microtubule-targeting agents may represent a novel strategy for future pharmacological approaches in the CDD field.

Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice.

BACKGROUND: Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic Mecp2 mutant mice, a model of Rett syndrome (RTT). AIM: The aim of this study was to provide further insights into the efficacy of CBDV in Mecp2-null mice using a lifelong treatment schedule (from 4 to 9 weeks of age) to evaluate its effect on recognition memory and neurological defects in both early and advanced stages of the phenotype progression. METHODS: CBDV 0.2, 2, 20 and 200 mg/kg/day was administered to Mecp2-null mice from 4 to 9 weeks of age. Cognitive and neurological defects were monitored during the whole treatment schedule. Biochemical analyses were carried out in brain lysates from 9-week-old wild-type and knockout mice to evaluate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) levels as well as components of the endocannabinoid system. RESULTS: CBDV rescues recognition memory deficits in Mecp2 mutant mice and delays the appearance of neurological defects. At the biochemical level, it normalizes BDNF/IGF1 levels and the defective PI3K/AKT/mTOR pathway in Mecp2 mutant mice at an advanced stage of the disease. Mecp2 deletion upregulates CB1 and CB2 receptor levels in the brain and these changes are restored after CBDV treatment. CONCLUSIONS: CBDV administration exerts an enduring rescue of memory deficits in Mecp2 mutant mice, an effect that is associated with the normalization of BDNF, IGF-1 and rpS6 phosphorylation levels as well as CB1 and CB2 receptor expression. CBDV delays neurological defects but this effect is only transient.

Balancing everyday life-Patients' experiences before, during and four months after kidney transplantation.

AIM: To explore patients' experiences before, during and four months after kidney transplantation as a coherent process. DESIGN: A qualitative explorative study with a phenomenological-hermeneutic approach. METHODS: Participant observations and semi-structured interviews were used complementary. In total, 18 kidney recipients were included. Data were analysed in accordance with Ricoeur's theory of interpretation, on three levels: naïve reading, structural analysis and critical interpretation and discussion. RESULTS: Three themes emerged: waiting time and hope during everyday life, transformation during the kidney transplantation process and towards a new everyday life with positive prospects. Going through the kidney transplantation process was challenging for the patients. Everyday life was affected through the process, and the patients had to balance the associated challenges like hope, positive prospects and health-related issues.

Physical exercise in the treatment of alcohol use disorder (AUD) patients affects their drinking habits: A randomized controlled trial.

AIM: The aim of this study is to compare the effect of exercise training on physical capacity and alcohol consumption in alcohol use disorder (AUD) patients. METHODS: One hundred and five AUD patients were randomly assigned to treatment as usual combined with running and brisk walking for 30-45 min twice a week, either in small supervised groups (GR) or individually (IND), or to a control group with no running (C). Assessments were made after 6 and 12 months of training. RESULTS: Training volume was estimated as 36 min per training bout at an intensity of 78% of HRmax with no differences between GR and IND ( p>.05). A highly significant reduction in training frequency was seen in both training groups after the first month ( p<.0001). Only IND increased VO2max, by 5.7% ( p<.05), while no differences were seen between GR, IND and C. Alcohol intake decreased from 219 to 41 units per 30 days as the average for the entire sample with no significant difference of drinking outcomes between groups ( p<.0001). CONCLUSIONS: We saw an effect on drinking habits after running in both groups. However, no additional effect was seen when compared with the control group. A drop in the training frequency during the intervention might have resulted in an insignificant training stimulus.