The dominant model that informs clinical training for preventing violence and managing aggression posits arousal as mediated downwards from higher cortical structures. This view results in an often-misplaced reliance on verbal and cognitive techniques for de-escalation. The emergence of sensory modulation, via the Six Core Strategies, is an alternative or complementary approach that is associated with reduced rates of seclusion and restraint. Sensory-based interventions are thought to promote adaptive regulation of arousal and emotion, but this connection has had limited theoretical and empirical development. This paper presents results of a pilot trial of sensory-based interventions in four inpatient mental health units in New Zealand. Narrative analysis of interview and focus group data suggest that modifications to the environment and the use of soothing stimuli moderate or optimize arousal and promote an ability to adaptively regulate emotion. Findings are discussed in light of recent advances in the neurophysiology of emotional regulation and the General Aggression Model that posits arousal and maladaptive emotional regulation as precursors to aggression.
The expression of the bone morphogenetic protein antagonist, Gremlin 1, was recently shown to be increased in the lungs of pulmonary arterial hypertension patients, and in response to hypoxia. Gremlin 1 released from the vascular endothelium may inhibit endogenous bone morphogenetic protein signaling and contribute to the development of pulmonary arterial hypertension. Here, we investigate the impact of Gremlin 1 inhibition in disease after exposure to chronic hypoxia/SU5416 in mice. We investigated the effects of an anti-Gremlin 1 monoclonal antibody in the chronic hypoxia/SU5416 murine model of pulmonary arterial hypertension. Chronic hypoxic/SU5416 exposure of mice induced upregulation of Gremlin 1 mRNA in lung and right ventricle tissue compared with normoxic controls. Prophylactic treatment with an anti-Gremlin 1 neutralizing mAb reduced the hypoxic/SU5416-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy. Importantly, therapeutic treatment with an anti-Gremlin 1 antibody also reduced pulmonary vascular remodeling and right ventricular hypertrophy indicating a role for Gremlin 1 in the progression of the disease. We conclude that Gremlin 1 plays a role in the development and progression of pulmonary arterial hypertension in the murine hypoxia/SU5416 model, and that Gremlin 1 is a potential therapeutic target for pulmonary arterial hypertension.
Since the 1990s, New Zealand mental health policy has shifted from a focus on the management of symptoms and risk to the recovery of psychological, social, cultural, and physical well-being. Despite a vision for recovery-oriented services being integrated within national and regional policies, there is growing concern that barriers to recovery-oriented service provision continue to exist. Such barriers include the attitudes, skills, and knowledge of front-line staff, as well as system issues. This study explored the experience and meaning of recovery-oriented practice for 10 nurses working in an acute inpatient mental health service. A phenomenological and hermeneutic lens was used to explore the nurses' experience of working in a recovery-focused manner alongside service users. Stories of practice were collected from participants through openended conversational interviews. Transcribed narratives were analysed to explore taken-forgranted aspects of working in acute mental health care and to uncover the meaning of being recovery-oriented in this setting. Findings revealed that although the experience and meaning of recovery-focused care varied among nurses, there were common elements in the practice accounts. The accounts highlighted the nurses' role in creating different therapeutic spaces to promote safety, relational commitment, and healing for service users. However, the nurses faced challenges to recovery-oriented care within the team hierarchical culture and the broader service systems. The nurses were, at times, fearless in advocating for service users and recognized that this was essential for developing recovery-focused services. The findings have implications for nursing practice, as well as training and service development.
BackgroundRepeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).Methodology/Principal FindingsMice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (RL) and dynamic compliance (Cdyn). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline RL and the decrease in baseline Cdyn caused by chronic exposure to inhaled HDM.Conclusions/SignificanceThese data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.
An
ever-increasing array of imaging technologies are being used
in the study of complex biological samples, each of which provides
complementary, occasionally overlapping information at different length
scales and spatial resolutions. It is important to understand the
information provided by one technique in the context of the other
to achieve a more holistic overview of such complex samples. One way
to achieve this is to use annotations from one modality to investigate
additional modalities. For microscopy-based techniques, these annotations
could be manually generated using digital pathology software or automatically
generated by machine learning (including deep learning) methods. Here,
we present a generic method for using annotations from one microscopy
modality to extract information from complementary modalities. We
also present a fast, general, multimodal registration workflow [evaluated
on multiple mass spectrometry imaging (MSI) modalities, matrix-assisted
laser desorption/ionization, desorption electrospray ionization, and
rapid evaporative ionization mass spectrometry] for automatic alignment
of complex data sets, demonstrating an order of magnitude speed-up
compared to previously published work. To demonstrate the power of
the annotation transfer and multimodal registration workflows, we
combine MSI, histological staining (such as hematoxylin and eosin),
and deep learning (automatic annotation of histology images) to investigate
a pancreatic cancer mouse model. Neoplastic pancreatic tissue regions,
which were histologically indistinguishable from one another, were
observed to be metabolically different. We demonstrate the use of
the proposed methods to better understand tumor heterogeneity and
the tumor microenvironment by transferring machine learning results
freely between the two modalities.
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