BACKGROUND AND PURPOSE: Flow diverters are increasingly used in the endovascular treatment of intracranial aneurysms. Our aim was to determine neurologic complication rates following Pipeline Embolization Device placement for intracranial aneurysm treatment in a real-world setting.

Tazarotene-induced protein 3 (TIG3) is a recently discovered regulatory protein that is expressed in the suprabasal epidermis. In the present study, we show that TIG3 regulates keratinocyte viability and proliferation. TIG3-dependent reduction in keratinocyte viability is accompanied by a substantial increase in the number of sub-G 1 cells, nuclear shrinkage, and increased formation of cornified envelope-like structures. TIG3 localizes to the membrane fraction, and TIG3-dependent differentiation is associated with increased type I transglutaminase activity. Microscopic localization and isopeptide cross-linking studies suggest that TIG3 and type I transglutaminase co-localize in membranes. Markers of apoptosis, including caspases and poly(ADP-ribose) polymerase, are not activated by TIG3, and caspase inhibitors do not stop the TIG3-dependent reduction in cell viability. Truncation of the carboxyl-terminal membrane-anchoring domain results in a complete loss of TIG3 activity. The morphology of the TIG3-positive cells and the effects on cornified envelope formation suggest that TIG3 is an activator of terminal keratinocyte differentiation. Our studies suggest that TIG3 facilitates the terminal stages in keratinocyte differentiation via activation of type I transglutaminase. TIG31 is a novel growth regulatory protein that is a member of the H-rev107 protein family (1). This family includes Hrev107 (2), RIG1/TIG3 (1, 3), H-rev107-1 (4), H-rev107-2 (4), and A-C1 (5). Immunostaining of epidermis reveals that TIG3 is expressed in the non-proliferating, suprabasal differentiated epidermal layers, but not in the proliferative basal cells (6), suggesting that TIG3 may play an important regulatory role during keratinocyte differentiation. TIG3 levels are reduced in tumor cells, consistent with the idea that the loss of TIG3 function may contribute to disease progression in cancer (1). However, the amino acid sequence of TIG3 does not reveal any particular motif that predicts a function, and no information is available regarding the TIG3 mechanism of action. Thus, identifying the mechanism of TIG3 action is an important goal that requires knowledge regarding the effects of TIG3 on cell regulatory mechanisms. In the present study, we show that TIG3 expression in cultured keratinocytes causes a cessation of cell proliferation and enhanced cornified envelope formation. Our results suggest that TIG3 associates with membranes and that the mechanism leading to reduced cell viability involves activation of type I transglutaminase. MATERIALS AND METHODSAdenovirus Infection-The tetracycline-regulated recombinant adenovirus, tAd5-TIG3 1-164 , was constructed by cloning the TIG3 1-164 coding sequence, linked to an SV40 transcription terminator, into tAd5. This adenoviral vector contains a tetracycline-responsive element that includes the cytomegalovirus promoter and tetracycline operator. Activation of this promoter requires the presence of the tetracycline transactivator (TA) protein that is provided by co-infection with a second aden...

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

The epidermis is a dynamic renewing structure that provides life-sustaining protection from the environment. The major cell type of the epidermis, the epidermal keratinocyte, undergoes a carefully choreographed program of differentiation. Alteration of these events results in a variety of debilitating and life-threatening diseases. Understanding how this process is regulated is an important current goal in biology. In this review, we summarize the literature regarding regulation of involucrin, an important marker gene that serves as a model for understanding the mechanisms that regulate the differentiation process. Current knowledge describing the role of transcription factors and signaling cascades in regulating involucrin gene expression are presented. These studies describe a signaling cascade that includes the novel protein kinase C isoforms, Ras, MEKK1, MEK3, and a p38delta-extracellular signal regulated kinase 1/2 complex. This cascade regulates activator protein one, Sp1, and CCATT/enhancer-binding protein transcription factor DNA binding to two discrete involucrin promoter regions, the distal- and proximal-regulatory regions, to regulate involucrin gene expression.

Background and Objective: Few prospective studies exist evaluating the safety and efficacy of the Pipeline Embolization Device (PED) in the treatment of intracranial aneurysms. The Aneurysm Study of Pipeline In an observational Registry (ASPIRe) study prospectively analyzed rates of complete aneurysm occlusion and neurologic adverse events following PED treatment of intracranial aneurysms. Materials and Methods: We performed a multicenter study prospectively evaluating patients with unruptured intracranial aneurysms treated with PED. Primary outcomes included (1) spontaneous rupture of the Pipeline-treated aneurysm; (2) spontaneous nonaneurysmal intracranial hemorrhage (ICH); (3) acute ischemic stroke; (4) parent artery stenosis, and (5) permanent cranial neuropathy. Secondary endpoints were (1) treatment success and (2) morbidity and mortality at the 6-month follow-up. Vascular imaging was evaluated at an independent core laboratory. Results: One hundred and ninety-one patients with 207 treated aneurysms were included in this registry. The mean aneurysm size was 14.5 ± 6.9 mm, and the median imaging follow-up was 7.8 months. Twenty-four aneurysms (11.6%) were small, 162 (78.3%) were large and 21 (10.1%) were giant. The median clinical follow-up time was 6.2 months. The neurological morbidity rate was 6.8% (13/191), and the neurological mortality rate was 1.6% (3/191). The combined neurological morbidity/mortality rate was 6.8% (13/191). The most common adverse events were ischemic stroke (4.7%, 9/191) and spontaneous ICH (3.7%, 7/191). The complete occlusion rate at the last follow-up was 74.8% (77/103). Conclusions: Our prospective postmarket study confirms that PED treatment of aneurysms in a heterogeneous patient population is safe with low rates of neurological morbidity and mortality. Patients with angiographic follow-up had complete occlusion rates of 75% at 8 months.

Object Postoperative infection after cranial surgery is a serious complication that requires immediate recognition and treatment. In certain cases such as postoperative meningitis, the patient can be treated with antibiotics only. In cases that involve a bone flap infection, subdural empyema, or cerebral abscess, however, reoperation is often needed. There has been significant disagreement regarding the incidence of postoperative central nervous system (CNS) infections following cranial surgery. In this paper the authors' goal was to perform a retrospective review of the incidence of CNS infection after cranial surgery at their institution. They focused their review on those patients who required repeated surgery to treat the infection. Methods The authors reviewed the medical records and imaging studies in all patients who underwent a craniotomy or stereotactic drainage for CNS infection over the past 10 years. Subgroup analysis was then performed in patients whose infection was a result of a previous cranial operation to determine the incidence, factors associated with infection, and the type of infectious organism. Patients treated nonoperatively (that is, those who received intravenous antibiotics for postoperative meningitis or cellulitis) were not included. Patients treated for wound infection without intracranial pus were also not included. Results During the study period from January 1997 through December 2007, ~ 16,540 cranial surgeries were performed by 25 neurosurgeons. These included elective as well as emergency and trauma cases. Of these cases 82 (0.5%) were performed to treat postoperative infection in 50 patients. All 50 patients underwent their original surgery at the authors' institution. The median age was 51 years (range 2–74 years). There were 26 male and 24 female patients. The most common offending organism was methicillin-sensitive Staphylococcus aureus, which was found in 10 of 50 patients. Gram-negative rods were found in 15 patients. Multiple organisms were identified in specimens obtained in 5 patients. Six patients had negative cultures. Most craniotomies leading to subsequent infection were performed for tumors or other mass lesions (23 of 50 patients), followed by craniotomies for hemorrhage and vascular lesions. Almost half of the patients underwent > 1 cranial operation before presenting with infection. Conclusions Postoperative infection after cranial surgery is an important phenomenon that needs immediate recognition. Even with strict adherence to sterile techniques and administration of antibiotic prophylaxis, a small percentage of these patients will develop an infection severe enough to require reoperation.

The epidermis is a dynamic and continually renewing surface that provides and maintains a life-sustaining interface with the environment. The epidermal keratinocyte, the major cell type of the epidermis, undergoes a complex and carefully choreographed program of differentiation. This process requires a balance between keratinocyte proliferation, differentiation, and apoptosis. This overview will concentrate on cascades that regulate the balance between keratinocyte cell proliferation and survival, and apoptosis and cell differentiation, with a particular emphasis on the role of the mitogen-activated protein kinase cascades. A summary of the literature suggests that extracellular regulated kinases function to promote keratinocyte proliferation and survival, whereas p38 mitogen-activated protein kinase functions to promote differentiation and apoptosis.

The p38 family of mitogen-activated protein kinases includes p38 alpha (SAPK2a, CSBP), p38 beta (SAPK2b), p38 delta (SAPK4), and p38 gamma (SAPK3/ERK6). p38 alpha and p38 beta are widely expressed p38 isoforms that are involved in regulation of cell proliferation, differentiation, development, and response to stress. Relatively less is known regarding the function of the p38 delta isoform. In this review, we discuss the role of the p38 alpha, p38 beta, and p38 gamma isoforms and then present recent findings that define a role for p38 delta as a regulator of differentiation-dependent gene expression in keratinocytes.