Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via the IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in the regulation of acute-phase protein genes in ...liver cells. Ligand binding to the receptor complex leads to tyrosine phosphorylation and activation of Janus kinases (Jak), phosphorylation of the signal transducing subunit gp130, followed by recruitment and phosphorylation of the signal transducer and activator of transcription factors STAT3 and STAT1 and the src homology domain (SH2)-containing protein tyrosine phosphatase (SHP2). The tyrosine phosphorylated STAT factors dissociate from the receptor, dimerize and translocate to the nucleus where they bind to enhancer sequences of IL-6 target genes. Phosphorylated SHP2 is able to bind growth factor receptor bound protein (grb2) and thus might link the Jak/STAT pathway to the ras/raf/mitogen-activated protein kinase pathway. Here we present data on the dose-dependence, kinetics and kinase requirements for SHP2 phosphorylation after the activation of the signal transducer, gp130, of the IL-6-type family receptor complex. When human fibrosarcoma cell lines deficient in Jak1, Jak2 or tyrosine kinase 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only in Jak1-, but not in Jak 2- or Tyk2-deficient cells, SHP2 activation was greatly impaired. It is concluded that Jak1 is required for the tyrosine phosphorylation of SHP2. This phosphorylation depends on Tyr-759 in the cytoplasmatic domain of gp130, since a Tyr-759-->Phe exchange abrogates SHP2 activation and in turn leads to elevated and prolonged STAT3 and STAT1 activation as well as enhanced acute-phase protein gene induction. Therefore, SHP2 plays an important role in acute-phase gene regulation.
LAY SUMMARY The way military personnel describe seeking support for difficult mental health experiences can highlight what helped recovery and what impeded it. This study examined stories of ...accessing care told by New Zealand Defence Force (NZDF) military members to understand their unique perspectives on mental health recovery. In total, 21 NZDF military personnel who were treated for mental health concerns were interviewed. Results showed how personnel described experiences of being supported through the NZDF mental health system, how hard it was to seek help, and how challenging the process was to get better. In general, participants described positive outcomes, where they felt supported to recover and become better versions of themselves through the process. Results highlight that growth from mental health struggles for NZDF military personnel is possible and can be supported. Discussion focuses on things leaders and organizations can do to ensure military service members are encouraged to feel they are in control of their own recovery process.
Introduction: Little is known about user experiences of accessing mental health care among active duty New Zealand Defence Force (NZDF) personnel. Although research exists on barriers to care and treatment outcomes, there is a dearth of understanding of the experiences between these two areas of focus. This study describes the narratives of 21 active duty personnel who sought mental health support in the NZDF health care system. Methods: Participant accounts were generated through semi-structured interviews and analysed using a narrative approach. The focus of analysis was to provide a deeper understanding of how participants storied their experiences from the onset of mental distress to recovery, with a focus on the narrative structure of these experiences. Results: Participant narratives often followed the progression of a quest narrative, mirroring the hero’s journey, which encompassed background factors leading to distress, chaos and breakdown, serendipitous connection to support, recovery, and redemption. Engaging with the health care system marked the beginning of personal transformation and posttraumatic growth. Transformation involved changing core beliefs and perspectives, leading to increased self-awareness and empathy and ultimately contributing to growth as individuals and leaders within the NZDF. Discussion: This study underscores the importance of understanding and facilitating posttraumatic growth in military personnel in both clinical and organizational contexts. It highlights the need for mental health messaging and support within military institutions to align with existing cultural values and narratives. Overall, the study contributes to a deeper understanding of the complex journey of recovery and growth in military mental health care contexts.
Mind wandering is common during daily activities and is even more prevalent under stressful conditions, which could lead to lapses in attention and poor performance. Newly recruited military ...personnel who undergo demanding training often experience high levels of stress. It is therefore imperative to find ways to foster mental health and avoid performance deterioration related to mind wandering in times of intense military training. This feasibility study investigated the effectiveness of an established low-dose mindfulness-based intervention (MBI), called Mindfulness-based Attention Training (MBAT), on mind wandering, attentional performance, and well-being, delivered by a facilitator who was taught how to deliver MBAT. A sample of newly recruited Royal New Zealand Navy (RNZN) Junior Officers (n = 17) undergoing demanding training participated in the 8-week long MBI with one weekly contact session. Measures of well-being and the Sustained Attention to Response Task (SART) were completed 4 weeks prior to the MBAT, at the start of the MBAT, at the end of the MBAT and 4 weeks after completion of the MBAT. Results suggest that MBAT might protect from performance decline during intense training and enhance levels of well-being at follow-up. These findings highlight the valuable role of mindfulness as a component in military training.
While the effectiveness of mindfulness‐based interventions (MBIs) with respect to distress has been widely researched, unemployed individuals, who often suffer from high levels of distress, have ...largely been neglected in MBI research. The present study aimed to investigate the effects of a low‐dose MBI on distress in a sample of young unemployed adults. The sample included 239 young unemployed adults enrolled for a 6‐week long employability‐related training camp. Participants were allocated into an intervention group that received weekly 1‐hour mindfulness training over 4 weeks, and a control group. Dispositional mindfulness, distress and well‐being were assessed in the entire sample prior to the start and upon completion of the mindfulness training. A mixed model ANCOVA showed that distress was inversely and significantly predicted by baseline levels of mindfulness and well‐being. After accounting for the baseline levels of mindfulness and well‐being, a significant effect of the mindfulness intervention was evident. This result shows that a low‐dose MBI can decrease distress in a sample of young unemployed adults and its effectiveness is positively associated with initial levels of dispositional mindfulness and well‐being.
The orientation to happiness framework proposes that individuals seek well-being through three behavioral orientations: Pleasure, meaning, and engagement. We investigated how orientations to ...happiness (OTH) influenced the pursuit and experience of daily activities using experience sampling methods. One hundred and seventy three people responded to three text messages per day for seven days asking how they felt about their current activity. Most participants did not report a dominant orientation to happiness, and the highest rated orientation receiving did not predict which daily activities participants engaged in most. However, trait orientation to happiness related to how activities were experienced. Individuals scoring highly on all three orientations rated their activities highly on momentary pleasure, meaning, engagement, and happiness. Overall, it appears more important for daily well-being to have a balanced and strong portfolio of the three OTH than to have any one particularly dominant orientation.
Objectives
Mindfulness has been shown to have beneficial effects with regard to improving well-being and lowering levels of distress. The Five Facet Mindfulness Questionnaire (FFMQ) has identified ...facets reflecting distinct mindfulness capacities, but it is not known yet to what extent they contribute individually to important outcomes such as well-being and distress. This study aimed to identify the most relevant facets and their unique contributions to distress and well-being to potentially enhance mindfulness-based interventions targeting these outcomes.
Methods
The present study assessed dispositional mindfulness, well-being and psychological distress in a sample of young adults (
n
= 239) and analyzed the differential contributions of mindfulness facets to distress and well-being outcome variables using stepwise multiple linear regression analyses.
Results
Individual differences in well-being and distress levels were best explained by different facets of mindfulness. The Nonreacting facet was the strongest contributor to well-being explaining 25% of variance in well-being scores, and after accounting for its contribution, Describing was the second largest contributor explaining additional 9%. In contrast, Acting with awareness was the strongest inverse contributor to distress explaining 20% variance and after controlling for it, Nonreacting explained merely 7% of additional differences in distress scores. After accounting for these main contributors, other facets explained only negligible amount of variance or were non-significant contributors.
Conclusions
The present study indicates that different capacities contribute differentially to well-being and distress. These findings may be useful for enhancing effectiveness of mindfulness-based interventions by tailoring practices to target well-being or psychological distress.
1. To quantify barriers to alcohol screening among hypertensive patients reported by primary healthcare professionals. 2. To examine whether education and screening frequency measures are associated ...with stigma-related barriers.
A web survey was conducted among 3081 primary healthcare professionals from France, Germany, Italy, Spain and the UK. Participants were asked about perceived barriers to alcohol screening as free-text response. The replies were independently categorized by two raters. Stigma-related barriers were predicted by logistic regressions with education, knowledge on alcohol as risk factor and frequency of alcohol screening.
In France and Italy, almost half of the reported barriers were stigma-related, whereas time constraints were cited most commonly in Spain and the UK. In Germany, nearly half of respondents rated the importance of alcohol screening for hypertension as low. Perception that regular screening is inappropriate or associated with too much effort, beliefs that screening is unnecessary, and insufficient knowledge of screening tools were cited as further barriers. Professional education on alcohol use was consistently rated to be poorer than the equivalent education on hypertension, and only a minority of respondents perceived alcohol as important risk factor for hypertension. Stigma-related barriers could not be significantly predicted by education, knowledge or screening frequency in most models.
Overall, regular alcohol screening among hypertensive patients seems to be widely accepted, but further education (Germany) and structural support (Spain, UK) could contribute to increase screening rates. In France and Italy, screening uptake could be improved by addressing stigma.
Alcohol screening among hypertensive patients was largely accepted among general practitioners from five different European countries. Reported screening barriers varied between countries and included time constraints, stigma and underrated importance of alcohol. Results did not indicate a positive impact of education and screening frequency on perception of stigma as barrier to screening.
The function of the signal-transducing receptor subunit glycoprotein 130 (gp130) in the IL-6-receptor complex has previously been studied using carboxyl-terminal deletion mutants or a truncated ...molecule of approximately 60 membrane-proximal amino acids (containing box 1 and box 2) linked to the individual gp130 tyrosine motifs. However, the redundancy of the tyrosine motifs within the cytoplasmic part of gp130 has been neglected. Here we describe the analysis of the function of the individual cytoplasmic tyrosine residues of gp130 in the context of the full-length receptor protein in IL-6 signaling as measured by STAT activation, acute phase protein induction, and stimulation of proliferation. Add-back receptor mutants containing only one cytoplasmic tyrosine have been generated and tested for their efficiency in IL-6 signal transduction. Our studies revealed that tyrosine motifs which have been described to recruit STAT proteins are not equivalent with respect to their potential to activate STAT factors and acute phase protein gene promoters: the two distal tyrosines, Tyr905 and Tyr915, of gp130 were more potent than Tyr767 and Tyr814. Surprisingly, Tyr905 and Tyr915 mediate acute phase protein gene promoter activation stronger than the wild-type receptor containing all six cytoplasmic tyrosine residues. In contrast, Ba/F3 cells stably transfected with add-back receptors containing Tyr767 or Tyr905 were more sensitive to IL-6-induced proliferation than cells expressing the other add-back receptor mutants. Thus, the tyrosine residues in the cytoplasmic part of gp130 were found to contribute differentially to IL-6 signal transduction in the full- length gp130 protein.
We augment a tree T with a shortcut pq to minimize the largest distance between any two points along the resulting augmented tree T+pq. We study this problem in a continuous and geometric setting ...where T is a geometric tree in the Euclidean plane, a shortcut is a line segment connecting any two points along the edges of T, and we consider all points on T+pq (i.e., vertices and points along edges) when determining the largest distance along T+pq. The continuous diameter is the largest distance between any two points along edges. We establish that a single shortcut is sufficient to reduce the continuous diameter of a geometric tree T if and only if the intersection of all diametral paths of T is neither a line segment nor a point. We determine an optimal shortcut for a geometric tree with n straight-line edges in O(nlogn) time.
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