Weinsteinhernandez7749

Podocytes are highly specialized cells within the glomerulus that are essential for ultrafiltration. The slit diaphragm between the foot processes of podocytes functions as a final filtration barrier to prevent serum protein leakage into urine. The slit-diaphragm consists mainly of Nephrin and Neph1, and localization of these backbone proteins is essential to maintaining the integrity of the glomerular filtration barrier. However, the mechanisms that regulate the localization of these backbone proteins have remained elusive. Here, we focused on the role of membrane-associated guanylate kinase inverted 2 (MAGI-2) in order to investigate mechanisms that orchestrate localization of slit-diaphragm backbone proteins. MAGI-2 downregulation coincided with a reduced expression of slit-diaphragm backbone proteins in human kidneys glomerular disease such as focal segmental glomerulosclerosis or IgA nephropathy. Podocyte-specific deficiency of MAGI-2 in mice abrogated localization of Nephrin and Neph1 independently of other scaffold proteins. Although a deficiency of zonula occuldens-1 downregulated the endogenous Neph1 expression, MAGI-2 recovered Neph1 expression at the cellular edge in cultured podocytes. Additionally, overexpression of MAGI-2 preserved Nephrin localization to intercellular junctions. Co-immunoprecipitation and pull-down assays also revealed the importance of the PDZ domains of MAGI-2 for the interaction between MAGI-2 and slit diaphragm backbone proteins in podocytes. Thus, localization and stabilization of Nephrin and Neph1 in intercellular junctions is regulated mainly via the PDZ domains of MAGI-2 together with other slit-diaphragm scaffold proteins. Hence, these findings may elucidate a mechanism by which the backbone proteins are maintained.The diuretic effects achieved with sodium glucose co-transporter 2 inhibitors (SGLT2i) may offset fluid retaining effects of the endothelin receptor antagonist (ERA) atrasentan while effects on albuminuria and kidney protection of both drug classes may be complimentary due to distinct mechanisms of action. Here, post-hoc analysis of the SONAR trial, in patients with type 2 diabetes and chronic kidney disease, show that six-weeks treatment with combined SGLT2i/atrasentan versus atrasentan alone decreased body weight, a surrogate for fluid retention, and further decreased albuminuria. Thus, these promising findings support future clinical studies to characterize the long-term efficacy and safety of combined SGLT2i/ERA treatment.Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria, and vascular injury in the second half of pregnancy. We hypothesized that endothelium-dependent vascular dysfunction is present in a murine model of preeclampsia based on administration of human preeclamptic sera to interleukin-10-/- mice and studied mechanisms that underlie vascular injury. Pregnant wild type and IL-10-/- mice were injected with either normotensive or severe preeclamptic patient sera (sPE) during gestation. A preeclampsia-like phenotype was confirmed by blood pressure measurements; assessment of albuminuria; measurement of angiogenic factors; demonstration of foot process effacement and endotheliosis in kidney sections; and by accumulation of glycogen in placentas from IL-10-/- mice injected with sPE sera (IL-10-/-sPE). Vasomotor function of isolated aortas was assessed. The IL-10-/-sPE murine model demonstrated significantly augmented aortic contractions to phenylephrine and both impaired endothelium-dependent and, to a lesser extent, endothelium-independent relaxation compared to wild type normotensive mice. Treatment of isolated aortas with indomethacin, a cyclooxygenase inhibitor, improved, but failed to normalize contraction to phenylephrine to that of wild type normotensive mice, suggesting the additional contribution from nitric oxide downregulation and effects of indomethacin-resistant vasoconstricting factors. In contrast, indomethacin normalized relaxation of aortas derived from IL-10-/-sPE mice. Thus, our results identify the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10-/-sPE murine model of preeclampsia and point towards a possible contribution of nitric oxide dysregulation. These compounds and related mechanisms may serve both as diagnostic markers and therapeutic targets for preventive and treatment strategies in preeclampsia.Epidermoid cysts (ECs) are benign extraaxial tumors. They frequently occur at the cerebellopontine angle and parasellar regions. However, they rarely occur in the Meckel's cave. Typically, ECs appear as a hypointense mass on T1-weighted magnetic resonance imaging (MRI) and hyperintense on T2-weighted MRI. However, ECs may occasionally present as hyperintense on T1-weighted imaging and hypointense on T2-weighted imaging. When this occurs, they are known as white epidermoid cysts. We present a case of a 25-year-old woman with a 3-month history of hypoesthesia in the distribution of the right trigeminal nerve. MRI showed a lesion located within the Meckel's cave. SR-25990C manufacturer The MRI signal was heterogeneous, with hyperintense areas on T1-weighted images, being hypointense on T2-weighted imaging. Preoperative suspicion was trigeminal schwannoma with unusual radiologic features. Finally, the pathologic diagnosis was epidermoid cyst. Therefore to establish a proper preoperative diagnosis, one should be aware that ECs can occur in Meckel's cave and with unusual radiologic features, as occurred in the case described earlier.

Multiple surgical specialties perform carotid endarterectomy (CEA). As indications for CEA narrows, neurosurgery residents are less exposed to this procedure. This study aims to determine trends in CEA training among graduating trainees in neurosurgery and compare these to general and vascular surgery.

ACGME case log reports were retrospectively reviewed from 2013 to 2019 for neurologic, general, and vascular surgery residencies and vascular surgery fellowship. These annual reports contain the mean number of logged cases for graduating trainees and their level of participation. We analyzed trends in logged cases over the study period and compared mean number of logged cases between specialties and their respective required minimum numbers.

Neurosurgery residents (13.5 ± 0.76) performed significantly more CEAs than their counterparts in general surgery (9.4 ± 0.34, P < 0.01) but less in integrated vascular surgery (57.7 ± 0.88) and vascular surgery fellowship (47.9 ± 0.79, both P < 0.001). The only statistically significant change over the study period was a decline in mean number of cases logged by general surgery residents at-0.