No abstract

Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glomerular hypertrophy was induced by progressive partial nephrectomies. Again, no significant podocyte replenishment was observed. Rather, labeled PECs exclusively invaded segments of the tuft affected by glomerulosclerosis, consistent with our previous findings. We next reassessed PEC recruitment in juvenile mice using a different reporter mouse and confirmed significant recruitment of labeled PECs onto the glomerular tuft. Moreover, some labeled cells on Bowman's capsule expressed podocyte markers, and cells on Bowman's capsule were also directly labeled in juvenile podocyte-specific Pod-rtTA transgenic mice. In 6-week-old mice, however, cells on Bowman's capsule no longer expressed podocyte-specific markers. Similarly, in human kidneys, some cells on Bowman's capsule expressed the podocyte marker synaptopodin from 2 weeks to 2 years of age but not at 7 years of age. In summary, podocyte regeneration from PECs could not be detected in aging mice or models of glomerular hypertrophy. We propose that a small fraction of committed podocytes reside on Bowman's capsule close to the vascular stalk and are recruited onto the glomerular tuft during infancy to adolescence in mice and humans.

Parietal epithelial cells (PECs) are crucially involved in the pathogenesis of rapidly progressive glomerulonephritis (RPGN) as well as in focal and segmental glomerulosclerosis (FSGS). In this study, transgenic mouse lines were used to isolate pure, genetically tagged primary cultures of PECs or podocytes using FACsorting. By this approach, the morphology of primary glomerular epithelial cells in culture could be resolved: Primary podocytes formed either large cells with intracytoplasmatic extensions or smaller spindle shaped cells, depending on specific culture conditions. Primary PECs were small and exhibited a spindle-shaped or polygonal morphology. In the very early phases of primary culture, rapid changes in gene expression (e.g. of WT-1 and Pax-2) were observed. However, after prolonged culture primary PECs and podocytes still segregated clearly in a transcriptome analysis - demonstrating that the origin of primary cell cultures is important. Of the classical markers, synaptopodin and podoplanin expression were differentially regulated the most in primary PEC and podocyte cultures. However, no expression of any endogenous gene allowed to differentiate between the two cell types in culture. Finally, we show that the transcription factor WT1 is also expressed by PECs. In summary, genetic tagging of PECs and podocytes is a novel and necessary tool to derive pure primary cultures with proven origin. These cultures will be a powerful tool for the emerging field of parietal epithelial cell biology.

German hospitals are now confronted with major challenges from both shortages and fluctuations in the numbers of physicians and nurses. This makes it even more important that physicians and nurses do not prematurely leave patient care. The objective of the present study was to improve our understanding of the factors that trigger intentions to leave the profession. For this purpose, data from 1060 young physicians and nurses in hospital care were analysed. Intentions to leave the profession was assessed with the Copenhagen Psychosocial Questionnaire (COPSOQ). In the first step, the association was determined between intention to leave the profession and the factors of perceived quality of care and job satisfaction. In a second step, a mediation analysis was performed to determine the effect of perceived quality of care after correction for the possible mediator of job satisfaction. There were statistically significant negative associations between perceived quality of care and intention to leave the profession (beta: −2.9, 95% CI: −4.48-−1.39) and job satisfaction and intention to leave the profession (beta: −0.5, 95% CI: −0.64-−0.44). The effect of perceived quality of care on intention to leave the profession was partially mediated by job satisfaction. Thus, high perceived quality of care and high job satisfaction are both important factors that tend to prevent young physicians and nurses from leaving their professions.for this include overtime, psychosocial stress, burnout, career aspects and particularly, a low level of job satisfaction [2][3][4][5][6]. In order to improve their balance between work and family, some physicians switch to nontherapeutic work or emigrate, in the hope of finding better working conditions in other countries [7].Although the absolute number of all physicians in Germany has been constantly increasing over the years [8], it is still justified to discuss a "relative lack of physicians" or a "lack of medical working hours". The reasons for this include the relatively high number of hospital beds (in comparison with other European countries), the imbalanced distribution between conurbations and rural areas, the fact that many physicians are very highly specialized, and finally the entry of more women into medicine [9]. At the end of 2018, it was found that women made up 47% of physicians registered at the German Medical Association [10]. This proportion is increasing, as is the proportion of female physicians who work part-time.The position was similar for nursing staff. Even during training, 20-30% of trainees were considering not remaining in the profession for more than 5 years [11]. Systematic reviews have proposed a wide variety of reasons that trained nursing staff may consider leaving the profession. These include inadequate earnings, lack of personnel, lack of autonomy and high stress at work [12][13][14]. At the individual level, these factors lead to low job satisfaction, which is also empirically associated with thoughts of leaving the profession [15][16][17][18][19][20][21]....

Why is it that only human beings continuously perform acts of heroism? Looking back at our evolutionary history can offer us some potentially useful insight. This review highlights some of the major steps in our evolution-more specifically, the evolution of high blood pressure. When we were fish, the first kidney was developed to create a standardized internal 'milieu' preserving the primordial sea within us. When we conquered land as amphibians, the evolution of the lung required a low systemic blood pressure, which explains why early land vertebrates (amphibians, reptiles) are such low performers. Gaining independence from water required the evolution of an impermeable skin and a water-retaining kidney. The latter was accomplished twice with two different solutions in the two major branches of vertebrate evolution: mammals excrete nitrogenous waste products as urea, which can be utilized by the kidney as an osmotic agent to produce more concentrated urine. Dinosaurs and birds have a distinct nitrogen metabolism and excrete nitrogen as water-insoluble uric acid-therefore, their kidneys cannot use urea to concentrate as well. Instead, some birds have developed the capability to reabsorb water from their cloacae. The convergent development of a separate small circulation of the lung in mammals and birds allowed for the evolution of 'high blood-pressure animals' with better capillarization of the peripheral tissues allowing high endurance performance. Finally, we investigate why mankind outperforms any other mammal on earth and why, to this day, we continue to perform acts of heroism on our eternal quest for personal bliss.