Memo1 gene expression in kidney and bone is unaffected by dietary mineral load and calciotropic hormones.

Mediator of cell motility 1 (MEMO1) is a ubiquitously expressed modulator of cellular responses to growth factors including FGF23 signaling, and Memo1-deficient mice share some phenotypic traits with Fgf23- or Klotho-deficient mouse models. Here, we tested whether Memo1 gene expression is regulated by calciotropic hormones or by changing the dietary mineral load. MLO-Y4 osteocyte-like cells were cultured and treated with 1,25(OH) <sub>2</sub> -vitamin D <sub>3</sub> . Wild-type C57BL/6N mice underwent treatments with 1,25(OH) <sub>2</sub> -vitamin D <sub>3</sub> , parathyroid hormone, 17β-estradiol or vehicle. Other cohorts of C57BL/6N mice were fed diets varying in calcium or phosphate content. Expression of Memo1 and control genes was assessed by qPCR. 1,25(OH) <sub>2</sub> -vitamin D <sub>3</sub> caused an acute decrease in Memo1 transcript levels in vitro, but not in vivo. None of the hormones tested had an influence on Memo1 transcripts, whereas the assessed control genes reacted the expected way. Dietary interventions with calcium and phosphate did not affect Memo1 transcripts but altered the chosen control genes' expression. We observed that Memo1 was not regulated by calciotropic hormones or change in mineral load, suggesting major differences between the regulation and physiological roles of Klotho, Fgf23, and Memo1

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Ways of calcium reabsorption in the kidney.

The role of the kidney in calcium homeostasis has been reshaped from a classic view in which the kidney was regulated by systemic calcitropic hormones such as vitamin D3 or parathyroid hormone to an organ actively taking part in the regulation of calcium handling. With the identification of the intrinsic renal calcium-sensing receptor feedback system, the regulation of paracellular calcium transport involving claudins, and new paracrine regulators such as klotho, the kidney has emerged as a crucial modulator not only of calciuria but also of calcium homeostasis. This review summarizes recent molecular and endocrine contributors to renal calcium handling and highlights the tight link between calcium and sodium reabsorption in the kidney

Risk Behavior and Reciprocity of Organ Donation Attitudes in Young Men.

BACKGROUND: Lack of donor organs remains a major obstacle in organ transplantation. Our aim was to evaluate (1) the association between engaging in high-risk recreational activities and attitudes toward organ donation and (2) the degree of reciprocity between organ acceptance and donation willingness in young men. METHODS: A 17-item, close-ended survey was offered to male conscripts ages 18 to 26 years in all Swiss military conscription centers. Predictors of organ donation attitudes were assessed in bivariate analyses and multiple logistic regression. Reciprocity of the intentions to accept and to donate organs was assessed by means of donor card status. RESULTS: In 1559 responses analyzed, neither motorcycling nor practicing extreme sports reached significant association with donor card holder status. Family communication about organ donation, student, or academic profession and living in a Latin linguistic region were predictors of positive organ donation attitudes, whereas residence in a German-speaking region and practicing any religion predicted reluctance. Significantly more respondents were willing to accept than to donate organs, especially among those without family communication concerning organ donation. CONCLUSIONS: For the first time, it was shown that high-risk recreational activities do not influence organ donation attitudes. Second, a considerable discrepancy in organ donation reciprocity was identified. We propose that increasing this reciprocity could eventually increase organ donation rates

Loss of Ecrg4 improves calcium oxalate nephropathy.

Kidney stone is one of the most frequent urinary tract diseases, affecting 10% of the population and displaying a high recurrence rate. Kidney stones are the result of salt supersaturation, including calcium and oxalate. We have previously identified Esophageal cancer-related gene 4 (Ecrg4) as being modulated by hypercalciuria. Ecrg4 was initially described as a tumor suppressor gene in the esophagus. Lately, it was shown to be involved as well in apoptosis, cell senescence, cell migration, inflammation and cell responsiveness to chemotherapy. To the best of our knowledge, nothing is known about ECRG4's function in the renal tissue and its relationship with calciuria. We hypothesized that the increased expression of Ecrg4 mRNA is triggered by hypercalciuria and might modulate intratubular calcium-oxalate precipitation. In this study, we have first (i) validated the increased Ecrg4 mRNA in several types of hypercalciuric mouse models, then (ii) described the Ecrg4 mRNA expression along the nephron and (iii) assessed ECRG4's putative role in calcium oxalate nephropathy. For this, Ecrg4 KO mice were challenged with a kidney stone-inducing diet, rich in calcium and oxalate precursor. Taken together, our study demonstrates that Ecrg4's expression is restricted mainly to the distal part of the nephron and that the Ecrg4 KO mice develop less signs of tubular obstruction and less calcium-oxalate deposits. This promotes Ecrg4 as a modulator of renal crystallization and may open the way to new therapeutic possibilities against calcium oxalate nephropathy

Redox-Dependent Bone Alkaline Phosphatase Dysfunction Drives Part of the Complex Bone Phenotype in Mice Deficient for <i>Memo1</i>.

Mediator of ErbB2-driven cell Motility 1 (MEMO1) is an intracellular redox protein that integrates growth factors signaling with the intracellular redox state. We have previously reported that mice lacking &lt;i&gt;Memo1&lt;/i&gt; displayed higher plasma calcium levels and other alterations of mineral metabolism, but the underlying mechanism was unresolved and the bone phenotype was not described. Here, we show that Cre/lox-mediated MEMO1 deletion in the whole body of C57Bl/6 mice (Memo cKO) leads to severely altered trabecular bone and lower mineralization, with preserved osteoblast and osteoclast number and activity, but altered osteoblast response to epidermal growth factor (EGF) and FGF2. More strikingly, Memo cKO mice display decreased alkaline phosphatase (ALP) activity in serum and in bone, while &lt;i&gt;ALPL&lt;/i&gt; expression level is unchanged. Bone intracellular redox state is significantly altered in Memo cKO mice and we inferred that ALP dimerization was reduced in Memo cKO mice. Indeed, despite similar ALP oxidation, we found increased ALP sensitivity to detergent in Memo cKO bone leading to lower ALP dimerization capability. Thus, we report a severe bone phenotype and dysfunctional bone ALP with local alteration of the redox state in Memo cKO mice that partially mimics hypophosphatasia, independent of &lt;i&gt;ALPL&lt;/i&gt; mutations. These findings reveal Memo as a key player in bone homeostasis and underline a role of bone redox state in controlling ALP activity

Narrativiteit in vaktherapie

Voor u ligt het boek ‘Narrativiteit in vaktherapie’, voor vaktherapeuten in de praktijk. Het doel van dit praktijkboek is om de begrippen ‘narratief werken’ en ‘narratief onderzoek’ toe te lichten en deze te verbinden aan de praktijk van de vaktherapie. Door definitie en uitleg van deze begrippen wordt het begrippenkader van de vaktherapeut itgebreid. Het helpt de vaktherapeut om te toetsen in hoeverre hij/zij werkzaam is volgens narratieve principes. Daarnaast schept het voor vaktherapeuten mogelijkheden hun werkwijzen desgewenst bij te schaven. Kennis over narrativiteit draagt zo bij aan de kwaliteit van het vaktherapeutisch werkveld