Therapeutic benefits of increasing natriuretic peptide levels

Natriuretic peptides play an important role in water and salt homeostasis and in the regulation of the cardiovascular system. In recent years, exogenous administration of natriuretic peptides has primarily been used to improve our understanding of the role of natriuretic peptides. Also, it became evident that natriuretic peptides may be used therapeutically. Because of their peptide character, they cannot be administered orally and, therefore, may be used for short-term intravenous therapy only. In recent years, inhibitors of neutral endopeptidase, which degrades natriuretic peptides to inactive metabolites, have been investigated. This review focuses on the potential benefits of increasing natriuretic peptide levels, either through exogenous administration or inhibiting the degradation of endogenous natriuretic peptide

Hallucinations in the general population across the adult lifespan:Prevalence and psychopathologic significance

Background: Community studies have found a relatively high prevalence of hallucinations, which are associated with a range of (psychotic and non-psychotic) mental disorders, as well as with suicidal ideation and behaviour. The literature on hallucinations in the general population has largely focused on adolescents and young adults. Aims: We aimed to explore the prevalence and psychopathologic significance of hallucinations across the adult lifespan. Method: Using the 1993, 2000, 2007 and 2014 cross-sectional Adult Psychiatric Morbidity Survey series (N = 33 637), we calculated the prevalence of past-year hallucinations in the general population ages 16 to ≥90 years. We used logistic regression to examine the relationship between hallucinations and a range of mental disorders, suicidal ideation and suicide attempts. Results: The prevalence of past-year hallucinations varied across the adult lifespan, from a high of 7% in individuals aged 16-19 years, to a low of 3% in individuals aged ≥70 years. In all age groups, hallucinations were associated with increased risk for mental disorders, suicidal ideation and suicide attempts, but there was also evidence of significant age-related variation. In particular, hallucinations in older adults were less likely to be associated with a cooccurring mental disorder, suicidal ideation or suicide attempt compared with early adulthood and middle age. Conclusions Our findings highlight important life-course developmental features of hallucinations from early adulthood to old age

Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice

Non-specific mental retardation (NSMR) is a common human disorder characterized by mental handicap as the only clinical symptom. Among the recently identified MR genes is GDI1, which encodes αGdi, one of the proteins controlling the activity of the small GTPases of the Rab family in vesicle fusion and intracellular trafficking. We report the cognitive and behavioral characterization of mice carrying a deletion of Gdi1. The Gdi1-deficient mice are fertile and anatomically normal. They appear normal also in many tasks to assess spatial and episodic memory and emotional behavior. Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory. In addition, they show lowered aggression and altered social behavior. In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations. The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive function

Consumer Law and Policy Relating to Change of Circumstances Due to the COVID-19 Pandemic

An unprecedented number of consumer problems has been caused by the COVID-19 pandemic, not least with regard to refunds of prepayments and the ability of consumers to keep up their monthly payments under loan and rental agreements. Based on a notion of societal force majeure sketched in this paper, we propose guiding principles in respect of the introduction of moratoria on recurring payments, the use of refunds or vouchers in respect of prepayments, and associated enforcement challenges. This analysis draws on experiences around the globe.Non peer reviewe

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

Friends or foes? migrants and sub-state nationalists in Europe

How do sub-state nationalists respond to the growing presence of cultural diversity in their ‘homelands’ resulting from migration? Sub-state nationalists in Europe, in ‘nations without states’ such as Catalonia and Scotland, have been challenging the traditional nation-state model for many decades. While the arguments in favour of autonomy or independence levelled by these movements have become more complex, sub-state nationalist movements remain grounded by their perceived national community that is distinct from the majority nation. Migration to the ‘homeland’ of a sub-state nation, then, presents a conundrum for sub-state elites that we label the ‘legitimation paradox’: too much internal diversity may undermine the claim to cultural distinctiveness. We engage with three common intervening variables thought to influence how sub-state nationalists confront the ‘legitimation paradox’: civic/ethnic nationalism, degree of political autonomy, and party competition. Our overarching argument is that none of these factors have a unidirectional or determinate effect on the sub-state nationalism-immigration nexus, which is why the nuanced case studies that comprise this Special Issue are worthwhile endeavours

Obliteration of radical cavities with autogenous cortical bone; long-term results

<p>Abstract</p> <p>Background</p> <p>To evaluate the long-term surgical outcome(s) in patients who have undergone canal-wall-down operation with mastoid and epitympanic obliteration using autologous cortical bone chips, bone pate and meatally-based musculoperiosteal flap technique.</p> <p>Method</p> <p>Retrospective evaluation of seventy patients operated during 1986–1991 due to a cholesteatoma. An otomicroscopy was performed to evaluate the postoperative outer ear canal configuration with a modified Likert scale (1 – 4). The outer ear canal physical volume was assessed by tympanometry. The hearing outcome and a patient-filled questionnaire were also analyzed.</p> <p>Results</p> <p>The posterior wall results were 1.8 (± 0.9 SD) and the attic region 1.8 (± 0.9 SD) (ns., p > 0.05). These values show either no cavity formation or minor formation of a cavity, with a good functional result. The mean volume of the operated ear canal was 1.7 (± 0.5 SD) ml. The volume of the contralateral ear canal was 1.2 (± 0.3 SD) ml (*** p < 0.0001). A comparison of the current mean ABG to the preoperative mean ABG and to the ABG at one-year postoperatively, 5-years postoperatively or 10-years postoperatively showed no statistical significance (p > 0.05).</p> <p>Conclusion</p> <p>ABG does not significantly change in the long-term. The configuration of the cavity tends to change, however, the obliteration material is stable in the long-term and clinically significant cavitation rarely occurs.</p