Feeding-elicited cataplexy in orexin knockout mice

Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad libitum regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 h after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy

Functional outcome and complications following surgery for Dupuytren’s disease: a multi-centre cross-sectional study

Variables associated with recurrent Dupuytren’s disease, or a ‘diathesis’, have been investigated, but those associated with functional outcome and complications are less well studied. Outcomes 1 or 5 years after an aponeurotomy, fasciectomy or dermofasciectomy were assessed by patient interview and examination at five UK centres. A total of 432 procedures were studied. The reoperation rate did not differ at 1 year (p = 0.396, Chi-square test with Monte Carlo simulation), but was higher after aponeurotomy in the 5-year group (30%, versus 6% after fasciectomy and 0% after dermofasciectomy, p = 0.003, Chi square test with Monte Carlo simulation). Loss of function (DASH>15) did not differ between procedures at 5 years, even when reoperation and other variables were controlled. Diabetes, female gender and previous ipsilateral surgery were associated with poorer function in logistic regression analysis. The variables associated with poor function after treatments differ from diathesis variables. Aponeurotomy had lower complication rates than fasciectomy and dermofasciectomy. This may counterbalance the former’s higher recurrence rate and explain why aponeurotomy demonstrated similar long-term functional outcome compared with excisional surgery in this study

Compassionate care in the community: reflections of a student nurse.

Reflecting on practice and analysing situations when compassionate care has been delivered can be a valuable way of helping student nurses develop their understanding of humanising care. This exemplar showcases a scenario when a second-year student nurse studying for a BSc (Honours) in adult nursing explored an experience while working in the community. She critically reflected on an incident highlighting a simple yet powerful example of how she helped an older couple manage an aspect of their care. This exercise helped the student to explore and understand what compassionate care means and highlighted how the value of reflection can be used to gain new insights to enhance the care of older people in her future practice in the community

Validity of the disabilities of the Arm, Shoulder and Hand patient-reported outcome measure (DASH) and the Quickdash when used in Dupuytren’s disease

This study investigated aspects of the validity and reliability of the 30-item Disabilities of the Arm, Shoulder and Hand patient-reported outcome measure (DASH) and its relationship with the shorter 11-item QuickDASH in patients with Dupuytren’s disease. Seven hundred and fifty-nine DASH questionnaires were studied, covering pre- and postoperative patients undergoing different treatments for Dupuytren’s disease. Items related to pain rose early after treatment before returning to baseline, suggesting that studying pain is relevant during postoperative recovery. Across all 759 sets of responses, the QuickDASH agreed closely with the DASH. In exploratory factor analysis, the DASH was not unidimensional, questioning the validity of the DASH summary score in Dupuytren’s disease. Further validation of existing PROMs for use in Dupuytren’s disease is needed. These data suggest that pain is a relevant symptom to study during postoperative recovery following treatment for Dupuytren’s disease

“Making voices heard…”: Index on Censorship as Advocacy Journalism

The magazine Index on Censorship has sought, since its launch in 1972, to provide a space where censorship and abuses against freedom of expression have been identified, highlighted and challenged. Originally set up by a collection of writers and intellectuals who were concerned at the levels of state censorship and repression of artists in and under the influence of the Soviet Union and elsewhere, ‘Index’ has provided those championing the values of freedom of expression with a platform for highlighting human rights abuses, curtailment of civil liberties and formal and informal censorship globally. Charting its inception and development between 1971 and 1974, the paper is the first to situate the journal within the specific academic literature on activist media (Janowitz, 1975; Waisbord, 2009; Fisher, 2016). In doing so the paper advances an argument which draws on the drivers and motivations behind the publication’s launch to signal the development of a particular justification or ‘advocacy’ of a left-libertarian civic model of freedom of speech

Cholinergic Modulation of Narcoleptic Attacks in Double Orexin Receptor Knockout Mice

To investigate how cholinergic systems regulate aspects of the sleep disorder narcolepsy, we video-monitored mice lacking both orexin (hypocretin) receptors (double knockout; DKO mice) while pharmacologically altering cholinergic transmission. Spontaneous behavioral arrests in DKO mice were highly similar to those reported in orexin-deficient mice and were never observed in wild-type (WT) mice. A survival analysis revealed that arrest lifetimes were exponentially distributed indicating that random, Markovian processes determine arrest lifetime. Low doses (0.01, 0.03 mg/kg, IP), but not a high dose (0.08 mg/kg, IP) of the cholinesterase inhibitor physostigmine increased the number of arrests but did not alter arrest lifetimes. The muscarinic antagonist atropine (0.5 mg/kg, IP) decreased the number of arrests, also without altering arrest lifetimes. To determine if muscarinic transmission in pontine areas linked to REM sleep control also influences behavioral arrests, we microinjected neostigmine (50 nl, 62.5 µM) or neostigmine + atropine (62.5 µM and 111 µM respectively) into the nucleus pontis oralis and caudalis. Neostigmine increased the number of arrests in DKO mice without altering arrest lifetimes but did not provoke arrests in WT mice. Co-injection of atropine abolished this effect. Collectively, our findings establish that behavioral arrests in DKO mice are similar to those in orexin deficient mice and that arrests have exponentially distributed lifetimes. We also show, for the first time in a rodent narcolepsy model, that cholinergic systems can regulate arrest dynamics. Since perturbations of muscarinic transmission altered arrest frequency but not lifetime, our findings suggest cholinergic systems influence arrest initiation without influencing circuits that determine arrest duration

Home-administered pre-surgical psychological intervention for knee osteoarthritis (HAPPiKNEES): study protocol for a randomised controlled trial

Background: Knee replacement surgery reduces pain for many people with osteoarthritis (OA). However, surgical outcomes are partly dependent on patients’ moods, and those with depression or anxiety have worse outcomes. Approximately one-third of people with OA have mood problems. Cognitive behavioural therapy (CBT), a psychological therapy, is recommended by the National Institute for Health and Care Excellence for improving mood. However, evidence for the effectiveness of CBT before knee surgery in improving pain, mood, and quality of life following this surgery for people with knee OA is lacking. Methods/Design: This is a multi-centre, mixed-methods feasibility randomised controlled trial to compare treatment as usual (TAU) plus a brief CBT-based intervention with a TAU-only control, for people with knee OA. We will recruit 50 patients with knee OA, listed for knee replacement surgery, with high levels of distress (assessed using a mood questionnaire), and who consent to take part. Participants will be randomly allocated to receive TAU plus intervention or TAU. Up to 10 sessions of CBT will be offered on an individual basis by a psychologist. The assessments and interventions will be completed before surgery. Repeat assessments at 4 and 6 months after randomisation will be sent and received by post. Two patient-partners will conduct feedback interviews with some participants to assess what aspects of the intervention were helpful or unhelpful, the acceptability of randomisation, the experience of being in a control group, and the appropriateness of the measures used. Interviews will be audio-recorded, transcribed, and analysed using the framework approach. We will examine the feasibility and acceptability of patient-partners conducting the interviews by also interviewing the patient-partners. Discussion: Findings from this study will be used to design a definitive study that will examine the clinical and cost-effectiveness of the CBT intervention in improving patient outcomes following knee surgery

Levels of resilience and delivery of HIV care in response to urban violence and crime

Aims To understand the impact of urban violence and crime on HIV care delivery. Background Urban violence and crime can put pressure on the health care system and on nursing staff. Whilst the impact this has at the individual level has been researched, there is less research that places this within the context of the overall social eco system. Design A qualitative design using inductive thematic analysis. Methods Between July 2016 February 2017, in‐depth interviews were conducted with 10 nurses working in two neighbourhoods with high levels of violence in Cape Town, South Africa. Results The effects of crime and violence were evident at multiple levels resulting in participants feeling ‘safe and unsafe’ in a context where crime is viewed as endemic. Resilience emerged as a key concept in the findings. Resilience was apparent at individual, community and organizational levels and enabled continued delivery of HIV care. Conclusion The findings demonstrate the potential role of resilience within the social eco‐health system required to sustain delivery of HIV care in the midst of urban violence and gangsterism. Impact This study examined the impact of and response to urban violence on HIV care delivery. The findings indicate that resilience manifests at all levels of the social eco‐system. Understanding the mechanisms employed to cope with endemic violence helps to address these challenges in the study setting, but also has a much wider application to other areas with endemic urban violence and crime

Circuit-based interrogation of sleep control.

Sleep is a fundamental biological process observed widely in the animal kingdom, but the neural circuits generating sleep remain poorly understood. Understanding the brain mechanisms controlling sleep requires the identification of key neurons in the control circuits and mapping of their synaptic connections. Technical innovations over the past decade have greatly facilitated dissection of the sleep circuits. This has set the stage for understanding how a variety of environmental and physiological factors influence sleep. The ability to initiate and terminate sleep on command will also help us to elucidate its functions within and beyond the brain

Apprehending public relations as a promotional industry

This special issue examines the growing social and political importance of promotional activities and public relations. For decades, promotional tools have been deployed to foster the aims of various societal agencies, be they corporations, political actors, public institutions, non-governmental organisations (NGOs) or citizen movements. In today’s turbulent political and media environments, promotional practices have become more inventive, coordinated and ubiquitous, crossing transnational borders and circulating across business, politics and social institutions. Public relations is an essential tool in the promotional mix and is increasingly a stand-alone strategy for organisations of all kinds to manage their visibility, legitimacy and relationships with stakeholders. However, its influence and power in the context of an increasingly promotional culture are under-researched. In this introduction, we set out the landscape of promotional culture in which public relations activity takes place and consider how existing research on promotional work may illuminate our knowledge of contemporary public relations work