ATP13A4 is a member of the subfamily of P5-type ATPases. P5-type ATPases are the least studied of the P-type ATPase subfamilies with no ion specificities assigned to them. In order to elucidate ATP13A4 function, we studied the protein's subcellular localization and tested whether it is involved in calcium regulation. The intracellular calcium concentration was measured in COS-7 cells over-expressing mouse ATP13A4 using ratiometric calcium imaging with fura-2 AM as a calcium indicator. The results of this study show that ATP13A4 is localized to the endoplasmic reticulum (ER). Furthermore, we demonstrate that over-expression of ATP13A4 in COS-7 cells caused a significant increase in the intracellular calcium level. Interestingly, over-expression of the sequence variant containing a substitution of aspartic acid for a glutamic acid (E646D), previously found in patients with autism spectrum disorder (ASD), did not increase the free cellular calcium likely due to the mutation. In this study, we also describe the expression of ATP13A4 during mouse embryonic development. Quantitative real-time PCR revealed that ATP13A4 was highly expressed at embryonic days 15-17, when neurogenesis takes place. The present study is the first to provide further insights into the biological role of a P5-type ATPase. Our results demonstrate that ATP13A4 may be involved in calcium regulation and that its expression is developmentally regulated. Overall, this study provides support for the hypothesis that ATP13A4 may play a vital role in the developing nervous system and its impairment can contribute to the symptoms seen in ASD.

IgG4-related disease (IgG4-RD) is a multi-organ chronic inflammatory process caused by infiltration of IgG4-positive plasma cells in one or more organs. Intracranial involvement has only recently become better recognized. Our case series adds to the growing literature on the varying presentations of intracranial IgG4 by describing the clinical and imaging findings of three patients who presented to our institution with intracranial involvement. Our first patient presented with a mass-forming IgG4 pachymeningitis mimicking a sphenoid wing meningioma, which is to our knowledge the largest mass-forming pachymeningitis published in the literature. Our second case depicts another presentation of extensive IgG4 pachymeningitis involving both cavernous sinuses and surrounding Meckel's caves. The third case describes a patient with presumed lymphocytic hypophysitis, which was later determined to be IgG4-related hypophysitis with concomitant pachymeningitis and perineural spread along the optic nerves. The delayed diagnoses in our cases illustrates the diagnostic challenge that clinicians face in differentiating intracranial IgG4-RD from other infiltrative diseases such as sarcoidosis, granulomatous disease, tuberculosis and lymphoma. Earlier consideration of IgG4-related hypophysitis and hypertrophic pachymeningitis in the differential diagnosis can prevent significant morbidity including unnecessary surgical intervention and organ failure secondary to extensive fibrosis.

There is a small but significant difference in pullout forces among various bridging stent-grafts. As pullout forces may be one factor contributing to type III endoleaks in complex endovascular repairs involving fenestrated and branched stent-grafts, further study is warranted to compare these grafts clinically to determine if they perform differently. According to this study, the theoretical advantages associated with the Viabahn stent-graft make it a strong choice for minimizing branch dislocations.

Angioplasty-first strategy for TransAtlantic Inter-Society Consensus C and D lesions of the femoro-popliteal artery can be safely performed. However, patency drastically decreases after 12 months suggesting further improvements are required to achieve longer-term clinical benefit.

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