The Aldosterone Paradox: differential regulation of the sodium chloride cotransporter

__Abstract__ Maintaining total body Na+ and K+ balance is essential to the survival of most species. Hypovolemia (Na+ deficit) and hyperkalemia (K+ surplus) elicit different constellations of responses to maintain homeostasis. During hypovolemia, the extracellular fluid volume needs to be maintained to guarantee blood pressure and organ perfusion. Conversely, during hyperkalemia, K+ secretion is stimulated to avoid cardiac and neuromuscular complications. Both these physiological conditions are regulated by the mineralocorticoid hormone aldosterone which is part of the renin-angiotensin-aldosterone system (RAAS). The observation that a single hormone, aldosterone, has different effects on renal Na+ and K+ transport, depending on the physiological situation, has been termed the “aldosterone paradox”. How the kidney “knows” when to retain Na+ or secrete K+ during these two high aldosterone states is unknown. To understand the aldosterone paradox, it is important to briefly review the regulation of Na+ and K+ transport in the kidney

Diagnostic and treatment procedures induced by cervical cancer screening

Abstract The amount of diagnostic and treatment procedures induced by cervical cancer screening has been assessed prospectively and related to mortality reduction. Assumptions are based on data from Dutch screening programmes and on a scenario for future developments. With 5 invitations for screening, between ages 37–70 every eight years, 13 deaths are avoided per million women per screening year. Each death avoided is balanced by 2800 preventive smears, 9 women referred to a gynaecology department and 4 minor treatment procedures (conserving treatment or exconisation). 25 invitations in a life-time avoids 27 deaths per million women per screening year but with 7300 preventive smears, 22 referrals and 8 small treatment procedures. Thus intensifying screening will not only result in diminishing returns of extra screening efforts, but also in increasing risk for women to undergo unnecessary (no invasive disease or death avoided) diagnostic and treatment procedures. The balance between beneficial and adverse effects deteriorates strongly when hysterectomies play an important part in the management of cervical intraepithelial neoplasia

Multi-frequency VEMPs improve detection of present otolith responses in bilateral vestibulopathy

ObjectiveTo investigate whether multi-frequency Vestibular Evoked Myogenic Potential (VEMP) testing at 500, 750, 1,000, and 2,000 Hz, would improve the detection of present dynamic otolith responses in patients with bilateral vestibulopathy (BV).MethodsProspective study in a tertiary referral center. BV patients underwent multi-frequency VEMP testing. Cervical VEMPs and ocular VEMPs were recorded with the Neuro-Audio system (v2010, Neurosoft, Ivanovo, Russia). The stimuli included air-conducted tone bursts of 500, 750, 1,000, and 2,000 Hz, at a stimulation rate of 13 Hz. Outcome measures included the percentage of present and absent VEMP responses, and VEMP thresholds. Outcomes were compared between frequencies and type of VEMPs (cVEMPs, oVEMPs). VEMP outcomes obtained with the 500 Hz stimulus, were also compared to normative values obtained in healthy subjects.ResultsForty-nine BV patients completed VEMP testing: 47 patients completed cVEMP testing and 48 patients completed oVEMP testing. Six to 15 % more present VEMP responses were obtained with multifrequency testing, compared to only testing at 500 Hz. The 2,000 Hz stimulus elicited significantly fewer present cVEMP responses (right and left ears) and oVEMP responses (right ears) compared to the other frequencies (p ≤ 0.044). Using multi-frequency testing, 78% of BV patients demonstrated at least one present VEMP response in at least one ear. In 46% a present VEMP response was found bilaterally. BV patients demonstrated a significantly higher percentage of absent VEMP responses and significantly higher VEMP thresholds than healthy subjects, when corrected for age (p ≤ 0.002). Based on these results, a pragmatic VEMP testing paradigm is proposed, taking into account multi-frequency VEMP testing.ConclusionMulti-frequency VEMP testing improves the detection rate of present otolith responses in BV patients. Therefore, multi-frequency VEMPs should be considered when evaluation of (residual) otolith function is indicated

Statistical mechanics of image restoration and error-correcting codes

We develop a statistical-mechanical formulation for image restoration and error-correcting codes. These problems are shown to be equivalent to the Ising spin glass with ferromagnetic bias under random external fields. We prove that the quality of restoration/decoding is maximized at a specific set of parameter values determined by the source and channel properties. For image restoration in mean-field system a line of optimal performance is shown to exist in the parameter space. These results are illustrated by solving exactly the infinite-range model. The solutions enable us to determine how precisely one should estimate unknown parameters. Monte Carlo simulations are carried out to see how far the conclusions from the infinite-range model are applicable to the more realistic two-dimensional case in image restoration.Comment: 20 pages, 9 figures, ReVTe

Evaluation of Interventions in Blended Learning Using a Communication Skills Serious Game

Serious games often employ a scripted dialogue for player interaction with a virtual character. In our serious game Communicate, a domain expert develops a structured, scripted scenario as a sequence of potential interactions in an authoring tool. A player is often a student learning communication skills and a virtual character represents a person that a student talks to. In the original version of Communicate, a player `converses' with a virtual character by clicking on one of the multiple statement options. Since 2018, we perform blended learning sessions for final year computer science students using Communicate. Our goal is to improve these sessions and in this paper, we apply the action research method over three semesters to iteratively improve these blended learning sessions. In the first semester, our baseline, we conduct sessions where students play a scenario in multiple choice format. In the second semester, we enhance Communicate by enabling a student to enter open text input in an improved scenario. In the third semester, we enhance a session by incorporating peer teaching. Students fill in an evaluation survey after a session and we compare the evaluation of students from the three semesters. Results show that student ratings are significantly higher in sessions incorporating peer teaching compared to the baseline

Endogenous attention modulates attentional and motor interference from distractors: Evidence from behavioral and electrophysiological results

Selective visual attention enhances the processing of relevant stimuli and filters out irrelevant stimuli and/or distractors. However, irrelevant information is sometimes processed, as demonstrated by the Simon effect (Simon and Rudell, 1967). We examined whether fully irrelevant distractors (task and target-irrelevant) produce interference (measured as the Simon effect), and whether endogenous orienting modulated this interference. Despite being fully irrelevant, distractors were attentionally coded (as reflected by the distractor-related N2pc component), and interfered with the processing of the target response (as reflected by the target-related lateralized readiness potential component). Distractors’ attentional capture depended on endogenous attention, and their interference with target responses was modulated by both endogenous attention and distractor location repetition. These results demonstrate both endogenous attentional and motor modulations over the Simon effect produced by fully irrelevant distractors.EM-A was supported by a predoctoral grant (AP2008-02806) from the FPU program from the Spanish Ministry of Education and Science, and by a postdoctoral grant from the INSERM-U1028. Research was funded by research projects PSI2008-03595PSIC, PSI2011-22416, and eraNET- NEURON BEYONDVIS, EUI2009-04082, to JL. FB was founded by a postdoctoral grant from the eraNET- NEURON BEYONDVIS project. ABC was supported with a Ramón y Cajal fellowship from the Spanish Ministry of Education and Science (RYC-2011-09320)

Mycophenolate mofetil attenuates DOCA-salt hypertension: Effects on vascular tone

Inflammation is increasingly recognized as a driver of hypertension. Both genetic and pharmacological inhibition of B and T cells attenuates most forms of experimental hypertension. Accordingly, the immunosuppressive drug mycophenolate mofetil (MMF) reduces blood pressure in the deoxycorticosterone acetate (DOCA-) salt model. However, the mechanisms by which MMF prevent hypertension in the DOCA-salt model remain unclear. Recent studies indicate that immunosuppression can inhibit sodium transporter activity in the kidney, but its effect on vascular tone is not well characterized. Therefore, the aim of the present study was to analyze the vascular and renal tubular effects of MMF in the DOCA-salt model in rats (4 weeks without uninephrectomy). Co-treatment with MMF attenuated the rise in blood pressure from day 11 onward resulting in a significantly lower telemetric mean arterial pressure after 4 weeks of treatment (108 ± 7 vs. 130 ± 9 mmHg, P < 0.001 by two-way analysis of variance). MMF significantly reduced the number of CD3+ cells in kidney cortex and inner medulla, but not in outer medulla. In addition, MMF significantly reduced urinary interferon-γ excretion. Vascular tone was studied ex vivo using wire myographs. An angiotensin II type 2 (AT2) receptor antagonist blocked the effects of angiotensin II (Ang II) only in the vehicle group. Conversely, L-NAME significantly increased the Ang II response only in the MMF group. An endothelin A receptor blocker prevented vasoconstriction by endothelin-1 in the MMF but not in the vehicle group. MMF did not reduce the abundances of the kidney sodium transporters NHE3, NKCC2, NCC, or ENaC. Together, our ex vivo results suggest that DOCA-salt induces AT2 receptor-mediated vasoconstriction. MMF prevents this response and increases nitric oxide availability. These data provide insight in the antihypertensive mechanism of MMF and the role of inflammation in dysregulating vascular tone

Expedition 361 summary

International Ocean Discovery Program Expedition 361 drilled six sites on the southeast African margin (southwest Indian Ocean) and in the Indian-Atlantic Ocean gateway, from 30 January to 31 March 2016. In total, 5175 m of core was recovered, with an average recovery of 102%, during 29.7 days of on-site operations. The sites, situated in the Mozambique Channel at locations directly influenced by discharge from the Zambezi and Limpopo River catchments, the Natal Valley, the Agulhas Plateau, and Cape Basin, were targeted to reconstruct the history of the greater Agulhas Current system over the past ~5 My. The Agulhas Current is the strongest western boundary current in the Southern Hemisphere, transporting some 70 Sv of warm, saline surface water from the tropical Indian Ocean along the East African margin to the tip of Africa. Exchanges of heat and moisture with the atmosphere influence southern African climates, including individual weather systems such as extratropical cyclone formation in the region and rainfall patterns. Recent ocean model and paleoceanographic data further point at a potential role of the Agulhas Current in controlling the strength and mode of the Atlantic Meridional Overturning Circulation (AMOC) during the Late Pleistocene. Spillage of saline Agulhas water into the South Atlantic stimulates buoyancy anomalies that may influence basin-wide AMOC, with implications for convective activity in the North Atlantic and global climate change. The main objectives of the expedition were to establish the role of the Agulhas Current in climatic changes during the Pliocene–Pleistocene, specifically to document the dynamics of the Indian-Atlantic Ocean gateway circulation during this time, to examine the connection of the Agulhas leakage and AMOC, and to address the influence of the Agulhas Current on African terrestrial climates and coincidences with human evolution. Additionally, the expedition set out to fulfill the needs of Ancillary Project Letter number 845, consisting of high-resolution interstitial water sampling to help constrain the temperature and salinity profiles of the ocean during the Last Glacial Maximum. The expedition made major strides toward fulfilling each of these objectives. The recovered sequences allowed generation of complete spliced stratigraphic sections that range from 0 to between ~0.13 and 7 Ma. This sediment will provide decadal- to millennial-scale climatic records that will allow answering the paleoceanographic and paleoclimatic questions set out in the drilling proposal