Digital Resilience Tactics of Syrian Refugees in the Netherlands: Social Media for Social Support, Health, and Identity

The process of adjusting to a new country may carry important stressors for refugees. In the light of neoliberal policies, refugees are expected to become resilient in a local arrival infrastructure and perform a specific subjectivity based on gratefulness, adaptability, and digital sensitivity to successfully integrate. Drawing on a qualitative, in-depth case study with Syrians living in the Netherlands, this article explores the impact of the retreat of the welfare state and unfolding digital transitions on resilience tactics of marginalized people like refugees. While recognizing the systemic violence and historic trauma many refugees have experienced, we focus on how refugees are expected to and develop ways to become resilient. Three digital resilience tactics are discussed: digital social support, digital health, and digital identities. Social support was mainly sought from family, friends, organizations, and social media platforms, whereas refugees’ engagement in meaningful digital practices aimed at fostering health promotion and identity management. Our fieldwork resurfaces paradoxes of digital resilience as described by careful emotional digital labor refugees engage in when communicating with families, the role of socio-cultural factors in shaping refugees’ ICT (information and communication technology) adoption and use for health support, and negotiation of different and conflicting identity axes online. Finally, our study provides some insights into the implementation of more effective online and offline practices in the context of social and health support by host countries

Dietary sodium induces a redistribution of the tubular metabolic workload.

Body Na <sup>+</sup> content is tightly controlled by regulated urinary Na <sup>+</sup> excretion. The intrarenal mechanisms mediating adaptation to variations in dietary Na <sup>+</sup> intake are incompletely characterized. We confirmed and expanded observations in mice that variations in dietary Na <sup>+</sup> intake do not alter the glomerular filtration rate but alter the total and cell-surface expression of major Na <sup>+</sup> transporters all along the kidney tubule. Low dietary Na <sup>+</sup> intake increased Na <sup>+</sup> reabsorption in the proximal tubule and decreased it in more distal kidney tubule segments. High dietary Na <sup>+</sup> intake decreased Na <sup>+</sup> reabsorption in the proximal tubule and increased it in distal segments with lower energetic efficiency. The abundance of apical transporters and Na <sup>+</sup> delivery are the main determinants of Na <sup>+</sup> reabsorption along the kidney tubule. Tubular O <sub>2</sub> consumption and the efficiency of sodium reabsorption are dependent on sodium diet. Na <sup>+</sup> excretion by the kidney varies according to dietary Na <sup>+</sup> intake. We undertook a systematic study of the effects of dietary salt intake on glomerular filtration rate (GFR) and tubular Na <sup>+</sup> reabsorption. We examined the renal adaptive response in mice subjected to 7 days of a low sodium diet (LSD) containing 0.01% Na <sup>+</sup> , a normal sodium diet (NSD) containing 0.18% Na <sup>+</sup> and a moderately high sodium diet (HSD) containing 1.25% Na <sup>+</sup> . As expected, LSD did not alter measured GFR and increased the abundance of total and cell-surface NHE3, NKCC2, NCC, α-ENaC and cleaved γ-ENaC compared to NSD. Mathematical modelling predicted that tubular Na <sup>+</sup> reabsorption increased in the proximal tubule but decreased in the distal nephron because of diminished Na <sup>+</sup> delivery. This prediction was confirmed by the natriuretic response to diuretics targeting the thick ascending limb, the distal convoluted tubule or the collecting system. On the other hand, HSD did not alter measured GFR but decreased the abundance of the aforementioned transporters compared to NSD. Mathematical modelling predicted that tubular Na <sup>+</sup> reabsorption decreased in the proximal tubule but increased in distal segments with lower transport efficiency with respect to O <sub>2</sub> consumption. This prediction was confirmed by the natriuretic response to diuretics. The activity of the metabolic sensor adenosine monophosphate-activated protein kinase (AMPK) was related to the changes in tubular Na <sup>+</sup> reabsorption. Our data show that fractional Na <sup>+</sup> reabsorption is distributed differently according to dietary Na <sup>+</sup> intake and induces changes in tubular O <sub>2</sub> consumption and sodium transport efficiency

Renal and Blood Pressure Response to a High-Salt Diet in Mice With Reduced Global Expression of the Glucocorticoid Receptor

Salt-sensitive hypertension is common in glucocorticoid excess. Glucocorticoid resistance also presents with hypercortisolemia and hypertension but the relationship between salt intake and blood pressure (BP) is not well defined. GRβgeo/+ mice have global glucocorticoid receptor (GR) haploinsufficiency and increased BP. Here we examined the effect of high salt diet on BP, salt excretion and renal blood flow in GRβgeo/+mice. Basal BP was ∼10 mmHg higher in male GRβgeo/+ mice than in GR+/+ littermates. This modest increase was amplified by ∼10 mmHg following a high-salt diet in GRβgeo/+ mice. High salt reduced urinary aldosterone excretion but increased renal mineralocorticoid receptor expression in both genotypes. Corticosterone, and to a lesser extent deoxycorticosterone, excretion was increased in GRβgeo/+ mice following a high-salt challenge, consistent with enhanced 24 h production. GR+/+ mice increased fractional sodium excretion and reduced renal vascular resistance during the high salt challenge, retaining neutral sodium balance. In contrast, sodium excretion and renal vascular resistance did not adapt to high salt in GRβgeo/+ mice, resulting in transient sodium retention and sustained hypertension. With high-salt diet, Slc12a3 and Scnn1a mRNAs were higher in GRβgeo/+ than controls, and this was reflected in an exaggerated natriuretic response to thiazide and benzamil, inhibitors of NCC and ENaC, respectively. Reduction in GR expression causes salt-sensitivity and an adaptive failure of the renal vasculature and tubule, most likely reflecting sustained mineralocorticoid receptor activation. This provides a mechanistic basis to understand the hypertension associated with loss-of-function polymorphisms in GR in the context of habitually high salt intake

Rôle du stress oxydant dans la rétention primaire de sodium et la constitution d'œdèmes au cours de syndrome néphrotique

Nephrotic Syndrome (NS) is a nonspecific kidney disorder defined by abnormal urinary excretion of plasma proteins and hypoalbuminemia. NS is always associated with a renal retention of Na+ leading to the generation of ascites and/or edema. The pathogenesis of Na+ retention and edema is not fully elucidated. In our studies we evaluated the possible role of reactive oxygen species (ROS) in this pathogenesis. Our studies in the puromycin aminonucleoside (PAN) rat model of NS provided pieces of evidence for a critical role of ROS in the hydro-electrolytic disorders associated with NS. In the kidney, endocytosis of abnormally filtered albumin in the distal nephron induces an oxidative stress which is responsible for the up-regulation of Na,K-ATPase. In the peritoneum, NS is associated with a marked increase in water permeability and a decrease in the reflection coefficient to proteins of the peritoneal barrier. These changes, which are triggered by oxidative stress and subsequent activation of NF-kB, account for approximately two-third of the volume of ascites. Finally, we confirmed that oxidative stress participates in the angiotensin-stimulated secretion of aldosterone and is required for the hyperaldosteronemia observed in PAN-nephrotic rats.Le syndrome néphrotique (SN) est causé par une altération glomérulaire, responsable d’une excrétion urinaire anormale de protéines plasmatiques, compliquée d’hypoalbuminémie. Le SN est toujours associé à une rétention rénale de Na + qui conduit à la génération d'ascite et / ou d'œdèmes. La pathogénie de la rétention de Na + et de la constitution d’œdèmes n’est pas entièrement élucidée. Dans notre étude, nous avons évalué le rôle possible des espèces réactives de l'oxygène (ROS) dans cette pathogénie. Notre étude dans le modèle de rat aminonucléoside puromycine (PAN) de SN fournit des éléments de preuve d'un rôle critique des ROS dans les troubles hydro-électrolytiques associés au SN. Dans le rein, l'endocytose de l'albumine anormalement filtrée dans le néphron distal induit un stress oxydatif qui est responsable de l’augmentation de la Na, K-ATPase. Dans le péritoine, le SN est associé à une augmentation marquée de la perméabilité à l'eau et à une diminution du coefficient de réflexion des protéines de la barrière péritonéale. Ces modifications, déclenchées par le stress oxydatif et l'activation subséquente de NF-kB, comptent pour environ deux tiers du volume de l'ascite. Enfin, nous avons confirmé que le stress oxydatif participe à la sécrétion de l'angiotensine-aldostérone et est nécessaire à l’apparition de l'hyperaldostéronémie observée chez les rats PAN-néphrotiques

Uninephrectomy and apical fluid shear stress decrease ENaC abundance in collecting duct principal cells

Acute nephron reduction such as after living kidney donation may increase the risk of hypertension. Uninephrectomy induces major hemodynamic changes in the remaining kidney, resulting in rapid increase of single-nephron glomerular filtration rate (GFR) and fluid delivery in the distal nephron. Decreased sodium (Na) fractional reabsorption after the distal tubule has been reported after uninephrectomy in animals preserving volume homeostasis. In the present study, we thought to specifically explore the effect of unilateral nephrectomy on epithelial Na channel (ENaC) subunit expression in mice. We show that γ-ENaC subunit surface expression was specifically downregulated after uninephrectomy, whereas the expression of the aldosterone-sensitive α-ENaC and α1-Na-K-ATPase subunits as well as of kidney-specific Na-K-Cl cotransporter isoform and Na-Cl cotransporter were not significantly altered. Because acute nephron reduction induces a rapid increase of single-nephron GFR, resulting in a higher tubular fluid flow, we speculated that local mechanical factors such as fluid shear stress (FSS) were involved in Na reabsorption regulation after uninephrectomy. We further explore such hypothesis in an in vitro model of FSS applied on highly differentiated collecting duct principal cells. We found that FSS specifically downregulates β-ENaC and γ-ENaC subunits at the transcriptional level through an unidentified heat-insensitive paracrine basolateral factor. The primary cilium as a potential mechanosensor was not required. In contrast, protein kinase A and calcium-sensitive cytosolic phospholipase A2 were involved, but we could not demonstrate a role for cyclooxygenase or epoxygenase metabolites

Oxidative Stress and Nuclear Factor κB (NF-κB) Increase Peritoneal Filtration and Contribute to Ascites Formation in Nephrotic Syndrome

International audienceWater accumulation in the interstitium (edema) and the peritoneum (ascites) of nephrotic patients is classically thought to stem from the prevailing low plasma albumin concentration and the decreased transcapillary oncotic pressure gradient. However, several clinical and experimental observations suggest that it might also stem from changes in capillary permeability. We addressed this hypothesis by studying the peritoneum permeability of rats with puromycin aminonucleoside-induced nephrotic syndrome. The peritoneum of puromycin aminonucleoside rats displayed an increase in the water filtration coefficient of paracellular and transcellular pathways, and a decrease in the reflection coefficient to proteins. It also displayed oxidative stress and subsequent activation of NF-κB. Scavenging of reactive oxygen species and inhibition of NF-κB prevented the changes in the water permeability and reflection coefficient to proteins and reduced the volume of ascites by over 50%. Changes in water permeability were associated with the overexpression of the water channel aquaporin 1, which was prevented by reactive oxygen species scavenging and inhibition of NF-κB. In conclusion, nephrotic syndrome is associated with an increased filtration coefficient of the peritoneum and a decreased reflection coefficient to proteins. These changes, which account for over half of ascite volume, are triggered by oxidative stress and subsequent activation of NF-κB

Expression of claudin-8 is induced by aldosterone in renal collecting duct principal cells.

Fine tuning of Na <sup>+</sup> reabsorption takes place along the aldosterone-sensitive distal nephron, which includes the collecting duct (CD), where it is mainly regulated by aldosterone. In the CD, Na <sup>+</sup> reabsorption is mediated by the epithelial Na <sup>+</sup> channel and Na <sup>+</sup> pump (Na <sup>+</sup> -K <sup>+</sup> -ATPase). Paracellular ion permeability is mainly dependent on tight junction permeability. Claudin-8 is one of the main tight junction proteins expressed along the aldosterone-sensitive distal nephron. We have previously shown a coupling between transcellular Na <sup>+</sup> reabsorption and paracellular Na <sup>+</sup> barrier. We hypothesized that aldosterone controls the expression levels of both transcellular Na <sup>+</sup> transporters and paracellular claudin-8 in a coordinated manner. Here, we show that aldosterone increased mRNA and protein levels as well as lateral membrane localization of claudin-8 in cultured CD principal cells. The increase in claudin-8 mRNA levels in response to aldosterone was prevented by preincubation with 17-hydroxyprogesterone, a mineralocorticoid receptor antagonist, and by inhibition of transcription with actinomycin D. We also showed that a low-salt diet, which stimulated aldosterone secretion, was associated with increased claudin-8 abundance in the mouse kidney. Reciprocally, mice subjected to a high-salt diet, which inhibits aldosterone secretion, or treated with spironolactone, a mineralocorticoid receptor antagonist, displayed decreased claudin-8 expression. Inhibition of glycogen synthase kinase-3, Lyn, and Abl signaling pathways prevented the effect of aldosterone on claudin-8 mRNA and protein abundance, suggesting that signaling of protein kinases plays a permissive role on the transcriptional activity of the mineralocorticoid receptor. This study shows that signaling via multiple protein kinases working in concert mediates aldosterone-induced claudin-8 expression in the CD.NEW & NOTEWORTHY In this study, we showed that aldosterone modulates claudin-8 expression in cultured collecting duct principal cells and in the mouse kidney. The upregulation of claudin-8 expression in response to aldosterone is dependent on at least glycogen synthase kinase-3, Lyn, and Abl signaling pathways, indicating the participation of multiple protein kinases to the effect of aldosterone

Dietary sodium intake does not alter renal potassium handling and blood pressure in healthy young males.

The effects of sodium (Na+) intakes on renal handling of potassium (K+) are insufficiently studied. We assessed the effect of Na+ on renal K+ handling in 16 healthy males assigned to three 7-day periods on low salt diet [LSD, 3 g sodium chloride (NaCl)/day], normal salt diet (NSD, 6 g NaCl/day) and high salt diet (HSD, 15 g NaCl/day), with constant K+ intake. Contributions of distal NaCl co-transporter and epithelial Na+ channel in the collecting system on K+ and Na+ handling were assessed at steady state by acute response to 100 mg oral hydrochlorothiazide and with addition of 10 mg of amiloride to hydrochlorothiazide, respectively. Diurnal blood pressure slightly increased from 119.30 ± 7.95 mmHg under LSD to 123.00 ± 7.50 mmHg (P = 0.02) under HSD, while estimated glomerular filtration rate increased from 133.20 ± 34.68 mL/min under LSD to 187.00 ± 49.10 under HSD (P = 0.005). The 24-h K+ excretion remained stable on all Na+ intakes (66.28 ± 19.12 mmol/24 h under LSD; 55.91 ± 21.17 mmol/24 h under NSD; and 66.81 ± 20.72 under HSD, P = 0.9). The hydrochlorothiazide-induced natriuresis was the highest under HSD (30.22 ± 12.53 mmol/h) and the lowest under LSD (15.38 ± 8.94 mmol/h, P = 0.02). Hydrochlorothiazide increased kaliuresis and amiloride decreased kaliuresis similarly on all three diets. Neither spontaneous nor diuretic-induced K+ excretion was influenced by Na+ intake in healthy male subjects. However, the respective contribution of the distal convoluted tubule and the collecting duct to renal Na+ handling was dependent on dietary Na+ intake