Effect of pH on the transport and adsorption of organic micropollutants in ion-exchange membranes in electrodialysis-based desalination

In energy-efficient electrodialysis desalination processes, salt ions are transported from seawater (high salinity) to wastewater (low salinity) through ion-exchange membranes. Besides salt ions, also organic micropollutants can be transported from wastewater (high in organics) to seawater (low in organics). The transport mechanisms of organic micropollutants through ion-exchange membranes are complex phenomena, and pH has a tremendous impact on them. Since pH variations in electrodialysis operation are common, it is of crucial importance to investigate its influence on these mechanisms. Therefore, a large pool of nineteen organic micropollutants of various physicochemical characteristics was selected and added to artificial wastewater, at environmentally relevant concentrations. Approximately twenty of these physicochemical properties were statistically analyzed to elucidate the dominant mechanisms affecting adsorption and transport of organic micropollutants as a function of pH. Additionally, the influence of different current densities on the transport of organic micropollutants at different pH conditions was studied. This pH effect has now been investigated for the very first time, leading to essential conclusions on the practical applicability of electrodialysis for seawater desalination. The presented findings advance our understanding of the type of interactions between organic micropollutants and ion-exchange membranes

Systematic clinical approach for diagnosing upper limb tremor

Tremor is the most common movement disorder worldwide, but diagnosis is challenging. In 2018, the task force on tremor of the International Parkinson and Movement Disorder Society published a consensus statement that proposes a tremor classification along two independent axes: a clinical tremor syndrome and its underlying aetiology. In line with this statement, we here propose a stepwise diagnostic approach that leads to the correct clinical and aetiological classification of upper limb tremor. We also describe the typical clinical signs of each clinical tremor syndrome. A key feature of our algorithm is the distinction between isolated and combined tremor syndromes, in which tremor is accompanied by bradykinesia, cerebellar signs, dystonia, peripheral neuropathy or brainstem signs. This distinction subsequently informs the selection of appropriate diagnostic tests, such as neurophysiology, laboratory testing, structural and dopaminergic imaging and genetic testing. We highlight treatable metabolic causes of tremor, as well as drugs and toxins that can provoke tremor. The stepwise approach facilitates appropriate diagnostic testing and avoids unnecessary investigations. We expect that the approach offered in this article will reduce diagnostic uncertainty and increase the diagnostic yield in patients with tremor

Call-duration and triage decisions in out of hours cooperatives with and without the use of an expert system

<p>Abstract</p> <p>Background</p> <p>Cooperatives delivering out of hours care in the Netherlands are hesitant about the use of expert systems during triage. Apart from the extra costs, cooperatives are not sure that quality of triage is sufficiently enhanced by these systems and believe that call duration will be prolonged drastically. No figures about the influence of the use of an expert system during triage on call duration and triage decisions in out of hours care in the Netherlands are available.</p> <p>Methods</p> <p>Electronically registered data concerning call duration and triage decisions were collected in two cooperatives. One in Tilburg, a cooperative in a Southern city of the Netherlands using an expert system, and one in Groningen, a cooperative in a Northern city not using an expert system. Some other relevant information about the care process was collected additionally. Data about call duration was compared using an independent sample t-test. Data about call decisions was compared using Chi Square.</p> <p>Results</p> <p>The mean call time in the cooperative using the TAS expert system is 4.6 minutes, in the cooperative not using the expert system 3.9 minutes. A significant difference of 0.7 minutes (0.4 – 1.0, 95% CI) minutes. In the cooperative with an expert system a larger percentage of patients is handled by the assistant, patients are less often referred to a telephone consultation with the GP and are less likely to be offered a visit by the GP.</p> <p>A quick interpretation of the impact of the difference in triage decisions, show that these may be large enough to support the hypothesis that longer call duration is compensated for by less contacts with the GP (by telephone or face-to-face). There is no proof, however, that these differences are caused by the use of the triage system. The larger amount of calls handled by the assistant may be partly caused by the fact that the assistants in the cooperative with an expert system more often consult the GP during triage. And it is not likely that the larger amount of home visits in Groningen can be attributed to the absence of an expert system. The expert system only offers advice whether a GP should be seen, not in which way (by consultation in the office or by home visit).</p> <p>Conclusion</p> <p>The differences in call times between a cooperative using an expert system and a cooperative not using an expert system are small; 0.4 – 1.0 min. Differences in triage decisions were found, but it is not proven that these can be contributed to the use of an expert system.</p

Amyotrophic lateral sclerosis (ALS)-associated VAPB-P56S inclusions represent an ER quality control compartment

BACKGROUND: Protein aggregation and the formation of intracellular inclusions are a central feature of many neurodegenerative disorders, but precise knowledge about their pathogenic role is lacking in most instances. Here we have characterized inclusions formed in transgenic mice carrying the P56S mutant form of VAPB that causes various motor neuron syndromes including ALS8.RESULTS: Inclusions in motor neurons of VAPB-P56S transgenic mice are characterized by the presence of smooth ER-like tubular profiles, and are immunoreactive for factors that operate in the ER associated degradation (ERAD) pathway, including p97/VCP, Derlin-1, and the ER membrane chaperone BAP31. The presence of these inclusions does not correlate with signs of axonal and neuronal degeneration, and axotomy leads to their gradual disappearance, indicating that they represent reversible structures. Inhibition of the proteasome and knockdown of the ER membrane chaperone BAP31 increased the size of mutant VAPB inclusions in primary neuron cultures, while knockdown of TEB4, an ERAD ubiquitin-protein ligase, reduced their size. Mutant VAPB did not codistribute with mutant forms of seipin that are associated with an autosomal dominant motor neuron disease, and accumulate in a protective ER derived compartment termed ERPO (ER protective organelle) in neurons.CONCLUSIONS: The data indicate that the VAPB-P56S inclusions represent a novel reversible ER quality control compartment that is formed when the amount of mutant VAPB exceeds the capacity of the ERAD pathway and that isolates misfolded and aggregated VAPB from the rest of the ER. The presence of this quality control compartment reveals an additional level of flexibility of neurons to cope with misfolded protein stress in the ER

PROGNOSTIC IMPLICATION OF THE MITRAL VALVE TENTING GEOMETRY IN PATIENTS WITH DILATED CARDIOMYOPATHY: TRANSTHORACIC REAL-TIME 3D ECHOCARDIOGRAPHIC STUDY

BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards

Unique tracheal fluid microRNA signature predicts response to FETO in patients with congenital diaphragmatic hernia

"Epub ahead of print 2015 Jan 5"OBJECTIVE AND BACKGROUND: Our objective was to determine the fetal in vivo microRNA signature in hypoplastic lungs of human fetuses with severe isolated congenital diaphragmatic hernia (CDH) and changes in tracheal and amniotic fluid of fetuses undergoing fetoscopic endoluminal tracheal occlusion (FETO) to reverse severe lung hypoplasia due to CDH. METHODS:: We profiled microRNA expression in prenatal human lungs by microarray analysis. We then validated this signature with real-time quantitative polymerase chain reaction in tracheal and amniotic fluid of CDH patients undergoing FETO. We further explored the role of miR-200b using semiquantitative in situ hybridization and immunohistochemistry for TGF-ß2 in postnatal lung sections. We investigated miR-200b effects on TGF-ß signaling using a SMAD-luciferase reporter assay and Western blotting for phospho-SMAD2/3 and ZEB-2 in cultures of human bronchial epithelial cells. RESULTS:: CDH lungs display an increased expression of 2 microRNAs: miR-200b and miR-10a as compared to control lungs. Fetuses undergoing FETO display increased miR-200 expression in their tracheal fluid at the time of balloon removal. Future survivors of FETO display significantly higher miR-200 expression than those with a limited response. miR-200b was expressed in bronchial epithelial cells and vascular endothelial cells. TGF-ß2 expression was lower in CDH lungs. miR-200b inhibited TGF-ß-induced SMAD signaling in cultures of human bronchial epithelial cells. CONCLUSIONS:: Human fetal hypoplastic CDH lungs have a specific miR-200/miR-10a signature. Survival after FETO is associated with increased miR-200 family expression. miR-200b overexpression in CDH lungs results in decreased TGF-ß/SMAD signaling

Engineering transient dynamics of artificial cells by stochastic distribution of enzymes

Here the authors develop a coacervate micromotor that can display autonomous motion as a result of stochastic distribution of propelling units. This stochastic-induced mobility is validated and explained through experiments and theory. Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors

SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid-base balance:secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes

Sodium-glucose transporter (SGLT)2 inhibitors increase plasma magnesium and plasma phosphate and may cause ketoacidosis, but the contribution of improved glycemic control to these observations as well as effects on other electrolytes and acid-base parameters remain unknown. Therefore, our objective was to compare the effects of SGLT2 inhibitors dapagliflozin and sulfonylurea gliclazide on plasma electrolytes, urinary electrolyte excretion, and acid-base balance in people with Type 2 diabetes (T2D). We assessed the effects of dapagliflozin and gliclazide treatment on plasma electrolytes and bicarbonate, 24-hour urinary pH and excretions of electrolytes, ammonium, citrate, and sulfate in 44 metformin-treated people with T2D and preserved kidney function. Compared with gliclazide, dapagliflozin increased plasma chloride by 1.4 mmol/l (95% CI 0.4-2.4), plasma magnesium by 0.03 mmol/l (95% CI 0.01-0.06), and plasma sulfate by 0.02 mmol/l (95% CI 0.01-0.04). Compared with baseline, dapagliflozin also significantly increased plasma phosphate, but the same trend was observed with gliclazide. From baseline to week 12, dapagliflozin increased the urinary excretion of citrate by 0.93 ± 1.72 mmol/day, acetoacetate by 48 μmol/day (IQR 17-138), and β-hydroxybutyrate by 59 μmol/day (IQR 0-336), without disturbing acid-base balance. In conclusion, dapagliflozin increases plasma magnesium, chloride, and sulfate compared with gliclazide, while reaching similar glucose-lowering in people with T2D. Dapagliflozin also increases urinary ketone excretion without changing acid-base balance. Therefore, the increase in urinary citrate excretion by dapagliflozin may reflect an effect on cellular metabolism including the tricarboxylic acid cycle. This potentially contributes to kidney protection

Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro

In a substantial part of adrenal adenomas and hyperplasias from patients with Cushing's syndrome, cortisol production is controlled by the expression of aberrant hormone receptors on adrenocortical cells. We present in vivo and in vitro data of two patients with a LH-responsive Cushing's syndrome based on ACTH-independent bilateral adrenal hyperplasia. Patients 1 and 2 are women who presented with Cushing's syndrome and bilateral adrenal hyperplasia. Endocrine testing demonstrated absence of cortisol diurnal rhythm, insufficient cortisol suppression after 1 mg dexamethasone orally, and undetectable ACTH levels in both patients. Both patients were treated by laparoscopic biadrenalectomy. In in vivo testing, in patients 1 and 2, a profound cortisol rise was found after administration of GnRH [change in cortisol (Delta F), 118 and 106%, respectively], human CG (Delta F, 133 and 44%), LH (Delta F, 73 and 43%), ACTH (Delta F, 89 and 181%), and the 5-hydroxy-tryptamine receptor type 4 (5-HT(4)) agonists cisapride (Delta F, 141 and 148%) and metoclopramide (Delta F, 189 and 95%). In in vitro testing, adrenal cells from patient 2 responded, in a dose-dependent fashion, with cortisol production after exposure to human CG (Delta F, 45%), cisapride (Delta F, 68%), and metoclopramide (Delta F, 81%). ACTH induced cortisol production by cells from both patients (Delta F, 135 and 159%). In receptor studies, LH receptor mRNA was demonstrated in adrenal tissue of both patients but also in control adrenal tissue of two patients with persisting pituitary-dependent Cushing's syndrome treated by biadrenalectomy. In neither patient were mutations found in the ACTH receptor gene. LH-responsive Cushing's syndrome associated with bilateral adrenal hyperplasia may result from aberrant (or possibly increased) adrenal LH receptor expression. This variant is further characterized by adrenal responsiveness to 5-HT4 receptor agonists, po

WASOG statement on the diagnosis and management of sarcoidosis-associated pulmonary hypertension

Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies