Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism

First described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5–10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk

Alkaline phosphatase in metastatic castration-resistant prostate cancer: reassessment of an older biomarker

Since most patients with metastatic castration-resistant prostate cancer (mCRPC) have bone metastases, it is important to understand the potential impact of therapies on prognostic biomarkers, such as ALP. Clinical studies involving mCRPC life-prolonging agents (i.e., sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, and radium-223) have shown that baseline ALP level is prognostic for overall survival, and may be a better prognostic marker for overall survival than prostate-specific antigen in patients with bone-dominant mCRPC. Mechanism of action differences between therapies may partly explain ALP dynamics during treatment. ALP changes can be interpreted within the context of other parameters while monitoring disease activity to better understand the underlying pathology. This review evaluates the current role of ALP in mCRPC

Why the visual recognition system might encode the effects of illumination

A key problem in recognition is that the image of an object depends on the lighting conditions. We investigated whether recognition is sensitive to illumination using 3-D objects that were lit from either the left or right, varying both the shading and the cast shadows. In experiments 1 and 2 participants judged whether two sequentially presented objects were the same regardless of illumination. Experiment 1 used six objects that were easily discriminated and that were rendered with cast shadows. While no cost was found in sensitivity, there was a response time cost over a change in lighting direction. Experiment 2 included six additional objects that were similar to the original six objects making recognition more difficult. The objects were rendered with cast shadows, no shadows, and as a control, white shadows. With normal shadows a change in lighting direction produced costs in both sensitivity and response times. With white shadows there was a much larger cost in sensitivity and a comparable cost in response times. Without cast shadows there was no cost in either measure, but the overall performance was poorer. Experiment 3 used a naming task in which names were assigned to six objects rendered with cast shadows. Participants practised identifying the objects in two viewpoints lit from a single lighting direction. Viewpoint and illumination invariance were then tested over new viewpoints and illuminations. Costs in both sensitivity and response time were found for naming the familiar objects in unfamiliar lighting directions regardless of whether the viewpoint was familiar or unfamiliar. Together these results suggest that illumination effects such as shadow edges: (1) affect visual memory; (2) serve the function of making unambigous the three-dimensional shape

Effective communication as a fundamental aspect of active aging and well-being: paying attention to the challenges older adults face in noisy environments

Successful communication is vital to active aging and well-being, yet virtually all older adults find it challenging to communicate effectively in noisy environments. The resulting discomfort and frustration can prompt withdrawal or avoidance of social situations, which, in turn, can severely limit the range of activities available to older adults and lead to a less active and satisfying lifestyle, and, in some cases, depression. Using the International Classification of Functioning, Disability and Health’s (ICF) multifactorial model (WHO, 2001), we review the wider aspects of functioning and disability as they relate to hearing difficulties and communication, placing a particular emphasis on the work we, an international and interdisciplinary group of researchers, have done in the context of the ERA-NET funded interdisciplinary HEARATTN project. The ICF model is particularly fitting because it allows us to consider how physiological changes in hearing and cognition affect listening in various situations, what the consequences of these changes are for communicative abilities and social participation, and how this in turn affects life-space mobility, self-reported well-being, and, ultimately, quality of life. We will discuss how environmental conditions (both physical and social) and personal factors can affect how well older adults can communicate in the situations characteristic of everyday life. In the concluding section we discuss some behaviors, techniques and strategies that can be adopted to maintain or improve effective communication under difficult listening conditions

Quantum walks of correlated photon pairs in two-dimensional waveguide arrays

We demonstrate quantum walks of correlated photons in a 2D network of directly laser written waveguides coupled in a 'swiss cross' arrangement. The correlated detection events show high-visibility quantum interference and unique composite behaviour: strong correlation and independence of the quantum walkers, between and within the planes of the cross. Violations of a classically defined inequality, for photons injected in the same plane and in orthogonal planes, reveal non-classical behaviour in a non-planar structure.Comment: 5 pages, 5 figure

Therapy of endocrine disease: Medical treatment of primary aldosteronism

In patients with primary aldosteronism, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension. Prognostic relevance has been shown for adrenalectomy in unilateral disease and for medical treatment with mineralocorticoid receptor antagonists in bilateral adrenal hyperplasia. Collectively, evidence points to the superiority of surgical treatment compared to medical treatment. The causal approach of removing the mineralocorticoid excess, as well as the often-accompanying glucocorticoid excess, might provide one biologically plausible explanation for the observation of slightly better outcomes with surgical therapy. However, in patients living with primary aldosteronism, medical treatment is often insufficient for three major reasons. First and foremost, no marker of sufficient aldosterone blockade has yet been established and therefore adequate treatment of the aldosterone excess is often dismissed as a treatment goal. Second, side effects often limit patient compliance. Third, as recommendations differ from other indications like heart failure, drug dosing is often inadequate. The aim of this review is first to provide an overview over medical treatment options and second to review potential markers for treatment surveillance in patients with primary aldosteronism

Memory Effects in Granular Material

We present a combined experimental and theoretical study of memory effects in vibration-induced compaction of granular materials. In particular, the response of the system to an abrupt change in shaking intensity is measured. At short times after the perturbation a granular analog of aging in glasses is observed. Using a simple two-state model, we are able to explain this short-time response. We also discuss the possibility for the system to obey an approximate pseudo-fluctuation-dissipation theorem relationship and relate our work to earlier experimental and theoretical studies of the problem.Comment: 5 pages, 4 figures, reference list change

Increased Heat Resilience of Intraspecific Outbred Compared to Inbred Lineages in the Kelp Laminaria digitata: Physiology and Transcriptomics

Marine forests and kelps as their foundation species are threatened by ocean warming especially at the warm distributional edges. Previously identified genetic divergence and ecotypic differentiation within kelp species may allow to produce more resilient lineages by intraspecific outbreeding among populations. In a mechanistic investigation of heat stress, heterosis (hybrid vigour), and underlying gene expression patterns, we assessed the thermal performance of inbred (selfings) and outbred (reciprocal crosses) sporophytes of the N-Atlantic kelp Laminaria digitata among clonal isolates from two divergent populations; one from the temperate North Sea (Helgoland) and one from the Arctic (Spitsbergen). First, we investigated the upper thermal tolerance of microscopic sporophytes in a 14-day experiment applying sublethal to lethal 20–23°C. The upper survival temperature of microscopic sporophytes was lower for the inbred Arctic selfing (21°C) than for the temperate selfing and the reciprocal crosses (22°C). Only in the temperate selfing, 4.5% of sporophytes survived 23°C. We then subjected 4–7 cm long sporophytes to a control temperature (10°C), moderate (19°C) and sublethal to lethal heat stress (20.5°C) for 18 days to assess gene expression in addition to physiological parameters. Growth and optimum quantum yield decreased similarly in the reciprocal crosses and the temperate selfing at 19 and 20.5°C, while inbred Arctic sporophytes died within seven days at both 19 and 20.5°C. In response to 20.5°C, 252 genes were constitutively regulated across all surviving lineages, which we use to describe metabolic regulation patterns in response to heat stress in kelp. At sublethal 20.5°C, ca. 150 genes were differentially expressed by either crossed lineage in comparison to the temperate selfing, indicating that they maintained a growth response similar to the temperate selfing with differential metabolic regulation during sublethal heat stress. Subtle differences in physiology and the differential expression of nine genes between the reciprocal crosses at 20.5°C indicate that female and male gametophytes may contribute differently to offspring traits. We consider potential inbreeding depression in the Spitsbergen selfing and quantify the better performance of both crosses using heterosis-related parameters. We discuss the potential and risks of outbreeding to produce more resilient crops for mariculture and marine forest restoration