Mutations in human KCNE2, which encodes the MiRP1 potassium channel ancillary subunit, associate with long QT syndrome (LQTS), a defect in ventricular repolarization. The precise cardiac role of MiRP1 remains controversial, in part, because it has marked functional promiscuity in vitro. Here, we disrupted the murine kcne2 gene to define the role of MiRP1 in murine ventricles. kcne2 disruption prolonged ventricular action potential duration (APD), suggestive of reduced repolarization capacity. Accordingly, kcne2 (-/-) ventricles exhibited a 50% reduction in I(K,slow1), generated by Kv1.5--a previously unknown partner for MiRP1. I(to,f), generated by Kv4 alpha subunits, was also diminished, by approximately 25%. Ventricular MiRP1 protein coimmunoprecipitated with native Kv1.5 and Kv4.2 but not Kv1.4 or Kv4.3. Unexpectedly, kcne2 (-/-) ventricular membrane fractions exhibited 50% less mature Kv1.5 protein than wild type, and disruption of Kv1.5 trafficking to the intercalated discs. Consistent with the reduction in ventricular K(+) currents and prolonged ventricular APD, kcne2 deletion lengthened the QT(c) under sevoflurane anesthesia. Thus, targeted disruption of kcne2 has revealed a novel cardiac partner for MiRP1, a novel role for MiRPs in alpha subunit targeting in vivo, and a role for MiRP1 in murine ventricular repolarization with parallels to that proposed for the human heart.

Invasive ductal carcinoma of the breast with clear cell changes is a very rare pathological entity. There are <150 cases of this breast cancer subtype reported in the literature. Clear cell carcinoma could be easily missed or under-diagnosed in a breast core biopsy specimen due to the fact that this subtype tends to show a papillary pattern with clear cell and pseudo-lactating changes, especially in young female patients. Normal breast tissue may possess clear cells as a consequence of the physiological changes of pregnancy, the clearing of the cytoplasm within myoepithelial cells, or the clearing of the cytoplasm in apocrine metaplasia. Owing to its aggressive clinical course, clear cell carcinoma must be differentiated from other subtypes of breast carcinoma. Special attention given to this rare subtype by pathologists and clinicians could avoid misdiagnosis and delay of treatment.

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Background Minimal aortic injury (MAI), a subtype of acute traumatic aortic injury, is being increasingly recognized with better imaging techniques. Given conservative management, the role of follow-up imaging albeit important yet has to be defined. Methods All trauma chest computed tomography angiographies (CTAs) at our center between January 2012 and January 2019 were retrospectively reviewed for presence of MAI. MAIs were generally reimaged at 24 to 72 hours and then at a 7- and 30-day interval. Follow-up CTAs were reviewed for stability, progression, or resolution of MAI, along with assessment of injury severity scores (ISS) and concomitant injuries, respectively. Results A total of 17,569 chest CTAs were performed over this period. Incidence of MAI on the initial chest CTA was 113 (0.65%), with 105 patients receiving follow-up CTAs. The first, second, third, and fourth follow-up CTAs were performed at a median of 2, 10, 28, and 261 days, respectively. Forty five (42.9%), 22 (21%), 5 (4.8%), and 1 (1%) of the MAIs were resolved by first, second, third, and fourth follow-up CTAs. Altogether, 21 patients showed stability (mean ISS of 16.6), and 11 demonstrated improvement (mean ISS 25.8) of MAIs. Eight patients had no follow-up CTA (mean ISS 21). No progression to higher-grade injury was observed. Advancing age decreased the odds of MAI resolution on follow-up. A possible trend (p-value 0.22) between increasing ISS and time to resolution of MAIs was noted. Conclusion In our series of acute traumatic MAIs diagnosed on CTA imaging, there was no progression of injuries with conservative management, questioning the necessity of sequential follow-up imaging.