Mechanism and reversal of drug-induced nephrotoxicity on a chip.

The kidney plays a critical role in fluid homeostasis, glucose control, and drug excretion. Loss of kidney function due to drug-induced nephrotoxicity affects over 20% of the adult population. The kidney proximal tubule is a complex vascularized structure that is particularly vulnerable to drug-induced nephrotoxicity. Here, we introduce a model of vascularized human kidney spheroids with integrated tissue-embedded microsensors for oxygen, glucose, lactate, and glutamine, providing real-time assessment of cellular metabolism. Our model shows that both the immunosuppressive drug cyclosporine and the anticancer drug cisplatin disrupt proximal tubule polarity at subtoxic concentrations, leading to glucose accumulation and lipotoxicity. Impeding glucose reabsorption using glucose transport inhibitors blocked cyclosporine and cisplatin toxicity by 1000- to 3-fold, respectively. Retrospective study of 247 patients who were diagnosed with kidney damage receiving cyclosporine or cisplatin in combination with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin showed significant (P < 0.001) improvement of kidney function, as well as reduction in creatinine and uric acid, markers of kidney damage. These results demonstrate the potential of sensor-integrated kidney-on-chip platforms to elucidate mechanisms of action and rapidly reformulate effective therapeutic solutions, increasing drug safety and reducing the cost of clinical and commercial failures.

Disruptive behaviors among nurses in Israel - association with listening, wellbeing and feeling as a victim: a cross-sectional study.

OBJECTIVES: To examine the association between listening and disruptive behaviors and the association between disruptive behavior and the wellbeing of the nurse. To test whether constructive and destructive listening has an incremental validity. METHODS: A structured questionnaire survey that measured the (constructive & destructive) listening climate at work, exposure to disruptive behaviors, well-being and feeling as a victim. We presented this survey using the Qualtrics software. RESULTS: Of the final sample of 567 respondents who reported that they were nurses, MAge = 38.41, 67% indicated that they were exposed to some form of disruptive behavior. Experiencing listening in the ward was associated with low levels of exposure to disruptive behaviors; exposure to disruptive behaviors, in turn, predicted reduction in the nurses' wellbeing; the reduction in wellbeing was especially pronounced among nurses who felt like a victim. Each of the facets of the listening measure-constructive listening and destructive listening-had incremental validity in predicting exposure to disruptive behaviors. Finally, the effect of exposure to disruptive behavior on wellbeing was curvilinear. CONCLUSIONS: Disruptive behavior is a major challenge to the workplace well-being for nurses. The victim mentality has an adverse impact on nurses. Preventive efforts aimed at reducing disruptive behaviors among nurses and decreasing their sense of victimization are crucial for the well-being of nurses.