Career success of preschool teachers in Germany – the significance of the Big Five personality traits,locus of control,and occupational self-efficacy

The career success of preschool teachers has been discussed to be important because it can be a precondition for the ability to provide a high-quality preschool education. Consequently, the identification of factors that can help explain individual differences in career success is a crucial research issue. Previous research covering various occupations indicates that the Big Five, internal locus of control (LOC), and occupational self-efficacy are good predictors of objective and subjective career success. However, there is a research gap on this topic in preschool teachers. This study examined whether the Big Five, LOC, and occupational self-efficacy could predict the career success of 560 preschool teachers in Germany. After controlling for other predictors, internal LOC corresponded with higher objective career success, but neuroticism and conscientiousness corresponded with lower subjective career success. Occupational self-efficacy corresponded with higher subjective career success. The findings are discussed with respect to practical conclusions.     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant – a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO₂/FiO₂ ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.     

Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays

BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma renin concentration (PRC). METHODS: We studied 76 healthy normotensive volunteers and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was determined by an activity assay. RESULTS: In volunteers, PAC varied from 33.3 to 1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1 pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35 to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU. In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(-1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and 6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU. Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff of 71 pmol/mU. CONCLUSION: The PAC/PRC ratio offers several practical advantages compared with the PAC/PRA screening method. The present study offers preliminary evidence that it may be a useful screening test for PHA. Further studies are required to validate these results, especially in hypertensive cohorts.     

A Protein Kinase A–Independent Pathway Controlling Aquaporin 2 Trafficking as a Possible Cause for the Syndrome of Inappropriate Antidiuresis Associated with Polycystic Kidney Disease 1 Haploinsufficiency

Renal water reabsorption is controlled by arginine vasopressin (AVP), which binds to V2 receptors, resulting in protein kinase A (PKA) activation, phosphorylation of aquaporin 2 (AQP2) at serine 256, and translocation of AQP2 to the plasma membrane. However, AVP also causes dephosphorylation of AQP2 at S261. Recent studies showed that cyclin-dependent kinases (cdks) can phosphorylate AQP2 peptides at S261 in vitro. We investigated the possible role of cdks in the phosphorylation of AQP2 and identified a new PKA-independent pathway regulating AQP2 trafficking. In ex vivo kidney slices and MDCK-AQP2 cells, R-roscovitine, a specific inhibitor of cdks, increased pS256 levels and decreased pS261 levels. The changes in AQP2 phosphorylation status were paralleled by increases in cell surface expression of AQP2 and osmotic water permeability in the absence of forskolin stimulation. R-Roscovitine did not alter cAMP-dependent PKA activity but specifically reduced protein phosphatase 2A (PP2A) expression and activity in MDCK cells. Notably, we found reduced PP2A expression and activity and reduced pS261 levels in Pkd1^+/− mice displaying a syndrome of inappropriate antidiuresis with high levels of pS256, despite unchanged AVP and cAMP. Similar to previous findings in Pkd1^+/− mice, R-roscovitine treatment caused a significant decrease in intracellular calcium in MDCK cells. Our data indicate that reduced activity of PP2A, secondary to reduced intracellular Ca²⁺ levels, promotes AQP2 trafficking independent of the AVP–PKA axis. This pathway may be relevant for explaining pathologic states characterized by inappropriate AVP secretion and positive water balance.In most mammals, regulation of water balance is critically dependent on water intake and excretion, which is under control of the antidiuretic hormone arginine vasopressin (AVP). In the kidney, AVP binds to the V2 vasopressin (V2R) receptor, activating the cAMP/protein kinase A (PKA) signal transduction cascade, promoting the fusion of intracellular vesicles containing aquaporin 2 (AQP2) to the apical plasma membrane, and increasing luminal permeability.^1–3 This translocation is accompanied by AVP-dependent phosphorylation of AQP2 at serine-256 (pS256).Mice in which S256 could not be phosphorylated (AQP2-S256L) develop polyuria and hydronephrosis because of a defect in AQP2 trafficking to the plasma membrane.⁴ Interestingly, it connects to polycystic kidney disease (PKD). Mutations in polycystin-1 (Pkd1^+/−) gene cause PKD, whereas PKD1 haplo-insufficient mice (Pkd1^+/−), showing an inappropriate antidiuresis, display significantly higher levels of pS256 compared with wild-type (WT) littermates; the prominent expression at the apical plasma membrane of collecting duct principal cells, despite normal V2R expression and normal cAMP levels, is associated with unchanged AVP expression in the brain, despite chronic hypo-osmolality.⁵These observations underscore the crucial role of AQP2 phosphorylation at S256 in controlling the cellular distribution and fate of AQP2.^1,6,7 As for many proteins, the function and the trafficking of AQP2 are modulated by a balance of reversible phosphorylation and dephosphorylation. Preventing dephosphorylation of AQP2 with okadaic acid, inhibitor of phosphatase 1 (PP1), inhibitor of phosphatase 2A (PP2A), and inhibitor of phosphatase 2B (PP2B) significantly increased AQP2-pS256.⁸ Proteomic analysis of inner medulla collecting duct identified PP2A as a phosphoprotein isolated from inner medullary collecting duct samples treated with either calyculin-A, a specific PP2A inhibitor, or vasopressin,⁹ suggesting the possible participation of this phosphatase in cellular events triggered by physiologic stimulus, such as vasopressin in renal collecting duct cells.The complexity of AQP2 regulation was further increased by phosphoproteomics studies showing that, other than S256, vasopressin modulates the phosphorylation status of three other sites within the C terminus (S261, S264, and S269). Although vasopressin increases S264 and S269 phosphorylation, it decreases S261 phosphorylation.^9–12 Regarding the potential kinases responsible for the phosphorylation of these sites, c-Jun N-terminal kinase, p38, and cyclin-dependent kinases (cdks) cdk1 and cdk5 can phosphorylate AQP2 peptides at S261 in vitro.^13,14 Here, in the attempt to investigate the potential involvement of cdks in AQP2 regulation, we discovered a new PKA-independent signal transduction pathway regulating AQP2 phosphorylation and localization. We found that selective inhibition of cdks with R-roscovitine is associated with a decrease of intracellular Ca²⁺ levels and a significant downregulation of the phosphatase PP2A activity, resulting in an increase of AQP2 phosphorylation at S256 and targeting to the apical membrane. Physiologically, this novel regulatory mechanism might be of clinical interest, because it better elucidates the molecular bases of pathologic states characterized by disturbances in water balance.