by
Samir K. Ballas;
Muge R. Kesen;
Morton F. Goldberg;
Gerard A. Lutty;
Carlton Dampier;
Ifeyinwa Osunkwo;
Winfred C. Wang;
Carolyn Hoppe;
Ward Hagar;
Deepika S. Darbari;
Punam Malik
The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the globin gene resulting in the substitution of glutamic acid by valine at position 6 of the globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Recent evidence suggests that grammatical aspect can bias how individuals perceive criminal intentionality during discourse comprehension. Given that criminal intentionality is a common criterion for legal definitions (e.g., first-degree murder), the present study explored whether grammatical aspect may also impact legal judgments. In a series of four experiments participants were provided with a legal definition and a description of a crime in which the grammatical aspect of provocation and murder events were manipulated. Participants were asked to make a decision (first- vs. second-degree murder) and then indicate factors that impacted their decision. Findings suggest that legal judgments can be affected by grammatical aspect but the most robust effects were limited to temporal dynamics (i.e., imperfective aspect results in more murder actions than perfective aspect), which may in turn influence other representational systems (i.e., number of murder actions positively predicts perceived intentionality). In addition, findings demonstrate that the influence of grammatical aspect on situation model construction and evaluation is dependent upon the larger linguistic and semantic context. Together, the results suggest grammatical aspect has indirect influences on legal judgments to the extent that variability in aspect changes the features of the situation model that align with criteria for making legal judgments.
High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007–1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.
To date, the fields of biomaterials science and tissue engineering have shown great promise in creating bioartificial tissues and organs for use in a variety of regenerative medicine applications. With the emergence of new technologies such as additive biomanufacturing and 3D bioprinting, increasingly complex tissue constructs are being fabricated to fulfill the desired patient-specific requirements. Fundamental to the further advancement of this field is the design and development of imaging modalities that can enable visualization of the bioengineered constructs following implantation, at adequate spatial and temporal resolution and high penetration depths. These in vivo tracking techniques should introduce minimum toxicity, disruption, and destruction to treated tissues, while generating clinically relevant signal-to-noise ratios. This article reviews the imaging techniques that are currently being adopted in both research and clinical studies to track tissue engineering scaffolds in vivo, with special attention to 3D bioprinted tissue constructs.
Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 matched slices (IVUS and OCT, baseline and follow-up) were obtained, and 3D thin-layer models were constructed to obtain stress and strain values. A generalized linear mixed model (GLMM) and least squares support vector machine (LSSVM) method were used to predict cap thickness change using nine morphological and mechanical risk factors. Prediction accuracies by all combinations (511) of those predictors with both IVUS and IO data were compared to identify optimal predictor(s) with their best accuracies. For the nine patients, the average of minimum cap thickness from IVUS was 0.17 mm, which was 26.08% lower than that from IO data (average = 0.23 mm). Patient variations of the individual errors ranged from ‒58.11 to 20.37%. For maximum cap stress between IO and IVUS, patient variations of the individual errors ranged from ‒30.40 to 46.17%. Patient variations of the individual errors of maximum cap strain values ranged from ‒19.90 to 17.65%. For the GLMM method, the optimal combination predictor using IO data had AUC (area under the ROC curve) = 0.926 and highest accuracy = 90.8%, vs. AUC = 0.783 and accuracy = 74.6% using IVUS data. For the LSSVM method, the best combination predictor using IO data had AUC = 0.838 and accuracy = 75.7%, vs. AUC = 0.780 and accuracy = 69.6% using IVUS data. This preliminary study demonstrated improved plaque cap progression prediction accuracy using accurate cap thickness data from IO slices and the differences in cap thickness, stress/strain values, and prediction results between IVUS and IO data. Large-scale studies are needed to verify our findings.
by
Guorong Li;
Chanyoung Lee;
Vibhuti Agrahari;
Ke Wang;
Iris Navarro;
Joseph M. Sherwood;
Karen Crews;
Sina Farsiu;
Pedro Gonzalez;
Cheng-Wen Lin;
Ashim K. Mitra;
Ross Ethier;
W. Daniel Stamer
Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm’s canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.