The long-term treatment of restless legs syndrome/Willis–Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group

AbstractA Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) to develop evidence-based and consensus-based recommendations for the long-term pharmacologic treatment of restless legs syndrome/Willis–Ekbom disease (RLS/WED). The Task Force reviewed the results of all studies of RLS/WED treatments with durations of 6months or longer presented at meetings over the past 2years, posted on Web sites of pharmaceutical companies, or published in peer-reviewed journals, asking the questions, “What is the efficacy of this treatment in patients with RLS/WED?” and “What is the safety of this treatment in patients with RLS/WED?”The Task Force developed guidelines based on their review of 61 papers meeting inclusion criteria, and using a modified evidence-grading scheme. Pregabalin has been established as effective for up to 1year in treating RLS/WED (Level A evidence). Pramipexole, ropinirole, and rotigotine have been established as effective for up to 6months in treating RLS/WED (Level A). The following drugs have been established as probably effective (Level B) in treating RLS/WED for durations ranging from 1 to 5years: gabapentin enacarbil, pramipexole, and ropinirole (1year); levodopa (2years); and rotigotine (5years). Because of associated safety concerns, pergolide and cabergoline should not be used in the treatment of RLS/WED unless the benefits clearly outweigh the risks. Other pharmacologic therapies have insufficient evidence to support their long-term use in treating RLS/WED.The IRLSSG Task Force also developed consensus-based strategies for the prevention and treatment of complications (such as augmentation, loss of efficacy, excessive daytime sleepiness, and impulse control disorders) that may develop with the long-term pharmacologic treatment of RLS/WED. The use of either a dopamine-receptor agonist or α2δ calcium-channel ligand is recommended as the first-line treatment of RLS/WED for most patients, with the choice of agent dependent on the patient’s severity of RLS/WED symptoms, cognitive status, history, and comorbid conditions

Catalytic Hydrogenation of Renewable Levulinic Acid to γ-Valerolactone:Insights into the Influence of Feed Impurities on Catalyst Performance in Batch and Flow Reactors

γ-Valerolactone (GVL) is readily obtained by the hydrogenation of levulinic acid (LA) and is considered a sustainable platform chemical for the production of biobased chemicals. Herein, the performance and stability of Ru-based catalysts (1 wt % Ru) supported on TiO2 (P25) and ZrO2 (monoclinic) for LA hydrogenation to GVL is investigated in the liquid phase in batch and continuous-flow reactors using water and dioxane as solvents. Particular attention is paid to the influence of possible impurities in the LA feed on catalyst performance for LA hydrogenation. Benchmark continuous-flow experiments at extended times on-stream showed that the deactivation profiles are distinctly different for both solvents. In dioxane, the Ru/ZrO2 catalyst is clearly more stable than Ru/TiO2, whereas the latter is slightly more stable in water. Detailed characterization studies on spent catalysts after long run times showed that the deactivation of Ru/TiO2 is strongly linked to the reduction of a significant amount of Ti4+ species of the support to Ti3+ and a decrease in the specific surface area of the support in comparison to the fresh catalyst. Ru/ZrO2 showed no signs of support reduction and displayed morphological and structural stability; however, some deposition of carbonaceous material is observed. Impurities in the LA feed such as HCOOH, H2SO4, furfural (FFR), 5-hydroxymethylfurfural (HMF), humins, and sulfur-containing amino acids impacted the catalyst performance differently. The results reveal a rapid yet reversible loss of activity for both catalysts upon HCOOH addition to LA, attributed to its preferential adsorption on Ru sites and possible CO poisoning. A more gradual drop in activity is found when cofeeding HMF, FFR, and humins for both solvents. The presence of H2SO4, cysteine, and methionine all resulted in the irreversible deactivation of the Ru catalysts. The results obtained provide new insights into the (ir)reversible (in)sensitivity of Ru-based hydrogenation catalysts to potential impurities in LA feeds, which is essential knowledge for next-generation catalyst development

The Sleep Quality- and Myopia-Linked PDE11A-Y727C Variant Impacts Neural Physiology by Reducing Catalytic Activity and Altering Subcellular Compartmentalization of the Enzyme

Recently, a Y727C variant in the dual-specific 3′,5′-cyclic nucleotide phosphodiesterase 11A (PDE11A-Y727C) was linked to increased sleep quality and reduced myopia risk in humans. Given the well-established role that the PDE11 substrates cAMP and cGMP play in eye physiology and sleep, we determined if (1) PDE11A protein is expressed in the retina or other eye segments in mice, (2) PDE11A-Y7272C affects catalytic activity and/or subcellular compartmentalization more so than the nearby suicide-associated PDE11A-M878V variant, and (3) Pde11a deletion alters eye growth or sleep quality in male and female mice. Western blots show distinct protein expression of PDE11A4, but not PDE11A1-3, in eyes of Pde11a WT, but not KO mice, that vary by eye segment and age. In HT22 and COS-1 cells, PDE11A4-Y727C reduces PDE11A4 catalytic activity far more than PDE11A4-M878V, with both variants reducing PDE11A4-cAMP more so than PDE11A4-cGMP activity. Despite this, Pde11a deletion does not alter age-related changes in retinal or lens thickness or axial length, nor vitreous or anterior chamber depth. Further, Pde11a deletion only minimally changes refractive error and sleep quality. That said, both variants also dramatically alter the subcellular compartmentalization of human and mouse PDE11A4, an effect occurring independently of dephosphorylating PDE11A4-S117/S124 or phosphorylating PDE11A4-S162. Rather, re-compartmentalization of PDE11A4-Y727C is due to the loss of the tyrosine changing how PDE11A4 is packaged/repackaged via the trans-Golgi network. Therefore, the protective impact of the Y727C variant may reflect a gain-of-function (e.g., PDE11A4 displacing another PDE) that warrants further investigation in the context of reversing/preventing sleep disturbances or myopia.</p

Emotion dysregulation mediates the relationship between nightmares and psychotic experiences: Results from a student population

Sleep-disruption is commonly associated with psychotic experiences. Whilst sparse, the literature to date highlights nightmares and related distress as prominent risk factors for psychosis in students. We aimed to further explore the relationship between specific nightmare symptoms and psychotic experiences in university students whilst examining the mediating role of emotion dysregulation. A sample (N=1273) of student respondents from UK universities completed measures of psychotic experiences, nightmare disorder symptomology, and emotion dysregulation. Psychotic experiences were significantly more prevalent in students reporting nightmares (n=757) relative to those who did not (n=516). Hierarchical linear regression analysis showed that psychotic experiences were significantly associated (Adjusted R2 = 32.4%) with perceived nightmare intensity, consequences and resulting awakenings, and with emotion regulation difficulties. Furthermore, multiple mediation analysis showed that the association between psychotic experiences and nightmare factors was mediated by emotion regulation difficulties. Adaptive regulation of dream content during rapid eye-movement sleep has previously been demonstrated to attenuate surges in affective arousal by controlling the intensity and variability of emotional content. Difficulties in emotion regulation may partially explain the experience of more intense and disruptive nightmares amongst individuals with psychotic experiences. Emotion regulation may represent an important control mechanism that safeguards dream content and sleep quality

Evolution of Wenger's concept of community of practice

<p>Abstract</p> <p>Background</p> <p>In the experience of health professionals, it appears that interacting with peers in the workplace fosters learning and information sharing. Informal groups and networks present good opportunities for information exchange. Communities of practice (CoPs), which have been described by Wenger and others as a type of informal learning organization, have received increasing attention in the health care sector; however, the lack of uniform operating definitions of CoPs has resulted in considerable variation in the structure and function of these groups, making it difficult to evaluate their effectiveness.</p> <p>Objective</p> <p>To critique the evolution of the CoP concept as based on the germinal work by Wenger and colleagues published between 1991 and 2002.</p> <p>Discussion</p> <p>CoP was originally developed to provide a template for examining the learning that happens among practitioners in a social environment, but over the years there have been important divergences in the focus of the concept. Lave and Wenger's earliest publication (1991) centred on the interactions between novices and experts, and the process by which newcomers create a professional identity. In the 1998 book, the focus had shifted to personal growth and the trajectory of individuals' participation within a group (i.e., peripheral versus core participation). The focus then changed again in 2002 when CoP was applied as a managerial tool for improving an organization's competitiveness.</p> <p>Summary</p> <p>The different interpretations of CoP make it challenging to apply the concept or to take full advantage of the benefits that CoP groups may offer. The tension between satisfying individuals' needs for personal growth and empowerment versus an organization's bottom line is perhaps the most contentious of the issues that make CoPs difficult to cultivate. Since CoP is still an evolving concept, we recommend focusing on optimizing specific characteristics of the concept, such as support for members interacting with each other, sharing knowledge, and building a sense of belonging within networks/teams/groups. Interventions that facilitate relationship building among members and that promote knowledge exchange may be useful for optimizing the function of these groups.</p

Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults

Introduction: The aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients. Methods: A systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients. Results: Safety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations. Conclusion: Consensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events

The prevalence of physical, sexual and mental abuse among adolescents and the association with BMI status

<p>Abstract</p> <p>Background</p> <p>Studies among adults show an association between abuse and Body Mass Index (BMI) status. When an aberrant BMI status as a consequence of abuse is already prevalent in adolescence, early detection and treatment of abuse might prevent these adolescents from developing serious weight problems and other long-term social, emotional and physical problems in adulthood. Therefore, this study investigated the prevalence of physical, sexual and mental abuse among adolescents and examined the association of these abuse subtypes with BMI status.</p> <p>Methods</p> <p>In total, data of 51,856 secondary school students aged 13–16 who had completed a questionnaire on health, well-being and lifestyle were used. BMI was classified into four categories, underweight, normal weight, overweight and obesity. Adolescents reported if they had ever been physically, sexually or mentally abused. Crude and adjusted General Estimation Equation (GEE) analyses were performed to investigate the association between abuse subtypes and BMI status. Analyses were adjusted for ethnicity and parental communication, and stratified for gender and educational level.</p> <p>Results</p> <p>Eighteen percent of the adolescents reported mental abuse, 7% reported sexual abuse, and 6% reported physical abuse. For underweight, overweight and obese adolescents these percentages were 17%, 25%, and 44%; 7%, 8%, and 16%; and 6%, 8%, 18% respectively. For the entire population, all these subtypes of abuse were associated with being overweight and obese (OR=3.67, 1.79 and 1.50) and all but sexual abuse were associated with underweight (OR=1.21 and 1.12). Stratified analyses showed that physical and sexual abuse were significantly associated with obesity among boys (OR=1.77 and 2.49) and among vocational school students (OR=1.60 and 1.69), and with underweight among girls (OR=1.26 and 0.83).</p> <p>Conclusion</p> <p>Mental abuse was reported by almost half of the obese adolescents and associated with underweight, overweight and obesity. Longitudinal analyses are recommended to explore the causality of and the mechanisms explaining this association between abuse and overweight.</p