Errors in cerebral blood flow determinations by xenon-enhanced computed tomography due to estimation of arterial xenon concentrations

Errors in the determination of xenon concentrations in arterial blood during inhalation of xenon-oxygen mixtures are used to assess errors in the derivation of regional cerebral blood flow by the xenon-enhanced computed tomography (CT) method. The results of this study indicate that approximating the arterial buildup by a single exponential introduces relatively small errors in estimated flow values. The most significant systematic error is introduced by errors in estimation of the xenon arrival time to the brain in relationship to sequential (CT) scanning times.     

Spline‐based self‐controlled case series method

The self‐controlled case series (SCCS) method is an alternative to study designs such as cohort and case control methods and is used to investigate potential associations between the timing of vaccine or other drug exposures and adverse events. It requires information only on cases, individuals who have experienced the adverse event at least once, and automatically controls all fixed confounding variables that could modify the true association between exposure and adverse event. Time‐varying confounders such as age, on the other hand, are not automatically controlled and must be allowed for explicitly. The original SCCS method used step functions to represent risk periods (windows of exposed time) and age effects. Hence, exposure risk periods and/or age groups have to be prespecified a priori, but a poor choice of group boundaries may lead to biased estimates. In this paper, we propose a nonparametric SCCS method in which both age and exposure effects are represented by spline functions at the same time. To avoid a numerical integration of the product of these two spline functions in the likelihood function of the SCCS method, we defined the first, second, and third integrals of I‐splines based on the definition of integrals of M‐splines. Simulation studies showed that the new method performs well. This new method is applied to data on pediatric vaccines. Copyright © 2017 John Wiley & Sons, Ltd.     

The effect of reperfusion therapy on cerebral blood flow in acute stroke.

The effect of reperfusion therapy on cerebral blood flow (CBF) in acute cerebral ischemia was studied using xenon-enhanced computed tomography (XeCT). The XeCT CBF studies of 10 patients were evaluated before and after thrombolytic therapy. CBF evidence of reperfusion was evaluated in relation to the angiographic results and the clinical outcomes. Six patients had occlusions of the middle cerebral artery and four of the internal carotid artery. The mean CBF of the ischemic areas before attempted reperfusion was 9 +/- 3 mL/100g/min compared with 34 +/- 9 mL/100g/min in the contralateral asymptomatic region (P<.001). Intra-arterial-thrombolysis was performed in nine patients, and in one patient the intravenous route was used. Reperfusion of the ischemic region was shown in 9 of 10 patients, both angiographically and with the XeCT CBF studies (the mean CBF increased from 9 +/- 3 mL/100g/min to 32 +/- 10 mL/100g/min, P<.001). Among the nine successfully reperfused patients, seven were neurologically improved, one was unchanged, and one died. The mean National Institutes of Health stroke scale in the eight reperfused survivors was 12 on admission and decreased to 6 on discharge. XeCT CBF measurements are correlated with the angiographic results and can assist in the understanding of the effects of thrombolytic therapy on CBF in acute stroke. Re-establishment of CBF is associated with an improved clinical outcome but exceptions can be found. Reperfusion can occur in ischemic brain regions even with very low CBF (approaching 0 mL/100g/min) although it is not associated with prevention of infarction.     

Predicting Progression to Mild Cognitive Impairment

Despite much attention to the use of biomarkers for predicting Alzheimer disease, little information is available at the individual level. We used the population‐based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality. For example, a 75‐year‐old with abnormal amyloid and cortical thinning biomarkers has about a 20% chance of cognitive impairment by age 80 years, whereas with normal biomarkers the chance is <10%. Persons with only one abnormal biomarker had similar intermediate risks. ANN NEUROL 2019;85:155–160.     

Apathy associated with neurocognitive disorders: Recent progress and future directions

Introduction

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities.

Inhibition of experimental metastasis by targeting the HUIV26 cryptic epitope in collagen

Metastasis from the primary tumor to distant sites involves an array of molecules that function in an integrated manner. Proteolytic remodeling and subsequent tumor cell interactions with the extracellular matrix regulate tumor invasion. In previous studies, we have identified a cryptic epitope (HUIV26) that is specifically exposed after alterations in the triple helical structure of type IV collagen. Exposure of this cryptic epitope plays a fundamental role in the regulation of angiogenesis in vivo. However, little is known concerning the ability of tumor cells to interact with this cryptic site or whether this site regulates tumor cell metastasis in vivo. In this regard, many of the same cellular processes that regulate angiogenesis also contribute to tumor metastasis. Here we provide evidence that tumor cells such as B16F10 melanoma interact with denatured collagen type IV in part by recognizing the HUIV26 cryptic site. Systemic administration of a HUIV26 monoclonal antibody inhibited experimental metastasis of B16F10 melanoma in vivo. Taken together, our findings suggest that tumor cell interactions with the HUIV26 cryptic epitope play an important role in regulating experimental metastasis and that this cryptic element may represent a therapeutic target for controlling the spread of tumor cells to distant sites.     

Adolescent dating violence: prevalence,risk factors,health outcomes,and implications for clinical practice

The goal of this synthesis is to provide a comprehensive assessment of the literature associated with dating violence in adolescence. Previous research findings on the prevalence, risk factors associated with victimization and perpetration, and potential health outcomes of dating violence are discussed. The importance of designing developmentally and culturally competent dating violence prevention and intervention strategies in the clinical setting is emphasized. This review is intended to assist health care professionals to develop interventions in their clinical settings to prevent and reduce adolescent dating violence.     

Integrins as “functional hubs” in the regulation of pathological angiogenesis

It is well accepted that complex biological processes such as angiogenesis are not controlled by a single family of molecules or individually isolated signaling pathways. In this regard, new insight into the interconnected mechanisms that regulate angiogenesis might be gained by examining this process from a more global network perspective. The coordination of signaling cues from both outside and inside many different cell types is required for the successful completion of angiogenesis. Evidence is accumulating that the multifunctional integrin family of cell adhesion receptors represent an important group of molecules that play active roles in sensing, integrating, and distributing a diverse set of signals that regulate many cellular events required for angiogenesis. Given the ability of integrins to bind numerous extracellular ligands and transmit signals in a bi-directional fashion, we will discuss the multiple ways by which integrins may serve as a functional hub during pathological angiogenesis. In addition, we will highlight potential imaging and therapeutic strategies based on the expanding new insight into integrin function.