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Anna B Banizs,1 Tao Huang,1 Kelly Dryden,2 Stuart S Berr,1 James R Stone,1 Robert K Nakamoto,2 Weibin Shi,1 Jiang He1 1Department of Radiology and Medical Imaging, 2Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA Abstract: Exosomes, one subpopulation of nanosize extracellular vesicles derived from multivesicular bodies, ranging from 30 to 150 nm in size, emerged as promising carriers for small interfering ribonucleic acid (siRNA) delivery, as they are capable of transmitting molecular messages between cells through carried small noncoding RNAs, messenger RNAs, deoxyribonucleic acids, and proteins. Endothelial cells are involved in a number of important biological processes, and are a major source of circulating exosomes. In this study, we prepared exosomes from endothelial cells and evaluated their capacity to deliver siRNA into primary endothelial cells. Exosomes were isolated and purified by sequential centrifugation and ultracentrifugation from cultured mouse aortic endothelial cells. Similar to exosome particles from other cell sources, endothelial exosomes are nanometer-size vesicles, examined by both the NanoSight instrument and transmission electron microscopy. Enzyme-linked immunosorbent assay analysis confirmed the expression of two exosome markers: CD9 and CD63. Flow cytometry and fluorescence microscopy studies demonstrated that endothelial exosomes were heterogeneously distributed within cells. In a gene-silencing study with luciferase-expressing endothelial cells, exosomes loaded with siRNA inhibited luciferase expression by more than 40%. In contrast, siRNA alone and control siRNA only suppressed luciferase expression by less than 15%. In conclusion, we demonstrated that endothelial exosomes have the capability to accommodate and deliver short foreign nucleic acids into endothelial cells. Keywords: extracellular vesicles, exosomes, gene delivery, siRNA, endothelium

We aim to bring awareness of allergies to excipients such as carboxymethylcellulose as “hidden dangers” that can be easily missed in diagnosis, leading to severe effects on patient health, and falsely limit the drug treatments that a patient can receive.

Gonadotropin-releasing hormone agonists are uncommonly associated with hypersensitivity reactions. To date, there have been few reports of these cases by allergists and no clear published protocols on testing. Here, we report the case of a patient who had a potential reaction to leuprolide acetate depot and a framework for assessing for drug hypersensitivity with the available literature in mind.

The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic Disorders and Stroke, industry representatives, and other traumatic brain injury stakeholders to attempt to reach consensus on issues related to and develop consensus recommendations in terms of creating both a well-characterized normative data base of comprehensive imaging and ancillary data to serve as a reference for tools that will allow interpretation of advanced neuroimaging tests at an individual level of a patient with traumatic brain injury. The workshop involved discussions concerning the following: 1) designation of the policies and infrastructure needed for a normative data base, 2) principles for characterizing normal control subjects, and 3) standardizing research neuroimaging protocols for traumatic brain injury. The present article summarizes these recommendations and examines practical steps to achieve them.

Penetrating cardiac injuries have a pre-hospital mortality of 94% with a subsequent in-hospital mortality of 50% among initial survivors (Leite et al., 2017 [1]). The Western Trauma Association (WTA) guidelines recommend resuscitative thoracotomy (RT) for patients with penetrating torso trauma and less than 15 min of cardiopulmonary resuscitation (CPR) Burlew et al. (2012) [2]. Penetrating cardiac injuries are classically repaired using skin-stapling devices and/or suture repair with or without pledgets (Wall et al., 1997 [3]). In this study, we present a case of penetrating cardiac injury where all the aforementioned techniques failed, and a new approach was explored. A fibrinogen/thrombin patch was used in this clinical setting, which is an off-label use of the product, we here present our encouraging outcome.

While design methods of deep foundations are mainly developed for homogenous soil deposits, the presence of highly cemented layers could lead to underestimation of resistance and overestimation of settlement of pile foundations. This study presents a novel approach using competent caliche layers bonded to the top and bottom of a continuous flight auger (CFA) pile as a new composite foundation system named caliche stiffened pile (CSP). The key objective is to optimize the required pile length in a cost-effective approach without ameliorating soil properties. Settlements of the CSP foundation for a high-rise building were monitored and full-scale tests were conducted to measure piles' capacity. Finite element back analyses were performed to avoid adverse effect of sample disturbance in settlement calculations. A back calculation of a test fill embankment was performed to determine soil stiffness parameters by simulating an unscheduled imposed load to the structure. Impacts of the CSP on controlling the settlement of pile foundation and optimizing the required pile length are investigated using finite element analysis and a parametric study. The proposed CSP foundation can reduce the CFA pile settlement significantly in the presence of caliche layers with thickness equal or greater than a pile diameter at CFA pile head and toe, where the CSP is located. [ABSTRACT FROM AUTHOR]

Background: Research has not yet examined how hot weather moderates the relationship between the built environment and outdoor physical activity levels. The authors posited that hot days will increase the magnitude of the expected directional effect of built environment features on physical activity. Methods: This longitudinal study included 134 US adults from the Three city Heat and Electrical failure AdapTation study. Adults self-reported physical activity for multiple summer days (nstudy-days = 742) in 2016. Hot days were defined as ≥90th percentile of daily maximum heat index. Built environment features included density, safety, trees, hilliness, connectivity, access to parks, and access to shops + services. Separate growth curve models with interaction terms (ie, hot day x built environment feature) were run for daily minutes of outdoor physical activity (ie, any activity and recommended activity). Results: Neither hot days nor built environment features impacted outdoor physical activity significantly, and hot days did not moderate the relationship between built environment features and physical activity (P > .05). Conclusions:With adults failing to modify behavior on hot days, cities may be placing adults at increased risk of exertional heat illness. The authors recommend incorporating the risk of exertional heat illness in health impact assessments and deploying heat management strategies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alpha-gal syndrome is an immunoglobulin E (IgE)-mediated delayed hypersensitivity reaction to nonprimate mammalian products, which has a newly established gastrointestinal (GI) phenotype in adults. We assessed the GI presentation and treatment response in children. METHODS: This is a retrospective study of patients presenting in a pediatric gastroenterology clinic tested for alpha-gal IgE. RESULTS: Forty of199patients (20%) tested had apositive alpha-gal-specific IgE,with77.5%reportingGIsymptomsin isolation. Of the 30 that attempted dietary elimination, 8 (27%) experienced full resolution of symptoms. DISCUSSION: Alpha-gal syndrome can present with isolated GI symptoms in children. [ABSTRACT FROM AUTHOR]

Indoor residential environments will be an increasing source of dangerous heat exposure as summer temperatures rise. Although air conditioning is a recognized preventative measure, many vulnerable residents either lack air conditioning or cannot always afford the electricity. Understanding the relative influence of different building characteristics and percentages of tree canopy coverage on indoor air temperatures during extreme heat events can help prioritize intervention strategies. We measured indoor and outdoor temperatures at 140 homes in Detroit (MI), Atlanta (GA), and Phoenix (AZ) and surveyed residents to determine the presence of a working central air-conditioning system and their ability to afford utilities. For each home, we collected information on construction year, interior size, single versus multifamily structure, façade type, and percentage of tree canopy. After air conditioning, the importance of building characteristics versus tree canopy measures varied by city. In Detroit, masonry façades worsened the influence of outdoor temperatures, whereas increased tree canopy coverage moderated the influence. In Atlanta, building characteristics were not significant, but tree canopy moderated indoor temperatures in late afternoon. In Phoenix, some building characteristics moderated the influence of outdoor temperatures in late afternoon. In Detroit, only 35% of respondents had and used central air conditioning as needed compared with 57% in Atlanta and 95% in Phoenix. The influence of tree canopy and building characteristics on indoor temperatures varied by city depending on its background climate. We recommend adding questions about air conditioning and utility poverty to the U.S. Census. For rental properties, municipalities should establish and enforce maximum indoor temperature thresholds. States should include cooling in their Low Income Home Energy Assistance (LIHEAP) programs. Public cooling centers need to anticipate electricity outages. Urban planners must ensure efforts to increase mechanical cooling are powered by renewable energy sources. [ABSTRACT FROM AUTHOR]

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I SCT has defined that living human systems function to survive, develop, and transform from simpler to more complex through the process of discriminating and integrating differences, differences in the apparently similar and similarities in the apparent differences. The Evolution of Ideas and Concepts Chapter three, entitled, "Transitions in SCT Theory and Practice 2013-2016" starts with these two sentences: "It is fundamental to SCT that systems-centered therapy is a theory-driven practice. This chapter explains how the Role Systems Map, a way of understanding the early development of role systems, helps the SCT practitioner to understand the maladaptive role systems. [Extracted from the article]

Background: Research groups are social locations where teaching and learning merge among students and a principal investigator (PI). When joining, some students are able to contribute to groundbreaking research that addresses complex problems, under the direction of their PI. However, there are accounts of students having a wide range of negative experiences, often at the hands of the PI. Despite the important roles that PIs play in the supervision of students, there is no standardized or required training for researchers holding these roles. As a result, some may replicate the practices they experienced—both positive and problematic. More knowledge is needed regarding group supervision for those in PI roles. Purpose: This autoethnographic longitudinal study explores students' experiences with and perceptions of PI supervision. The findings from this study offer insights into the design of group practices for current PIs and emerging researchers interested in serving as group PIs. Research Design: To better understand the culture of our own research group, and thus students' experiences with and perceptions of the PI's role in supervision, this study included 23 student group members in 12 focus group interviews over four years. Basic qualitative analysis techniques were used to document, identify, and examine our group's nuanced cultural practices and norms. Findings: Findings reveal balanced perspectives on four PI practices: (1) communicating clearly and validating group members works best in person; (2) providing transparency and reducing uncertainty is desired; (3) inclusive group composition is created through intentional recruitment practices; and (4) group size and member transitions need to be managed to maintain stability. Taken together, student group members believed these PI practices to be both beneficial and challenging to the group's learning, cohesion, and productivity. The findings also show that group members' desires and expectations may at times be in conflict. Conclusions: Being a PI offers a unique opportunity to develop new approaches that benefit a group's research and the learning of all of its members. Learning from students' experiences with and perceptions of their PI in this study, we hope that current and future group PIs will consider how they compose practices for their groups and support student members through research. Creating new approaches to group supervision may create healthier models for current and future researchers to implement in their own research practices. [ABSTRACT FROM AUTHOR]

Within scientific teams, a culture of community (the facilitation of shared values, goals, and an environment where individuals feel valued and want to engage in a team's work) has implications for members' learning and participation, and the team's functioning, cohesion, and productivity. Drawing on 12 focus group interviews conducted over four years with 23 participants, we used an autoethnographic approach to examine how a research team developed a positive culture of community that influences its cohesion and productivity. We present six interconnected cultural practices that can foster a culture of community in settings where team-based learning and collaborations are required. [ABSTRACT FROM AUTHOR]

Summary: Understanding how the voice is used in different styles of singing is commonly based on intuitive descriptions offered by performers who are proficient ill only one style. Such descriptions [...]

As of June, nine political leaders had thrown their hats in the ring as candidates for the Republican nomination to challenge Bill Clinton in 1996. Policy Review asked a conservative [...]

Objective: There is paucity of data about prevalence of pediatric acute respiratory distress syndrome (PARDS) in children with pulmonary contusion (PC). We intend to evaluate PC in children with chest trauma and the association between PC and PARDS. Design: Retrospective review of Institutional Trauma Registry for patients with trauma. Setting: Level 1 trauma center. Patients: Age 18 years and younger with a diagnosis of PC. Interventions: None. Measurements and Main Results: Of the 1916 children with trauma, 50 (2.6%) had PC. Patients with PC and PARDS had lower Glasgow Coma Scale (GCS) score (7 [3-15] vs 15 [15-15], P = .0003), higher Injury Severity Scale (ISS) score (29 [22-34] vs 19 [14-22], P = .004), lower oxygen saturations (96 [93-99] days vs 99 [98-100] days, P = .0009), higher FiO2 (1 [1-1] vs 0.21 [0.21-0.40], P < .0001), lower oxygen saturation/FiO2 (S/F) ratios (97 [90-99] vs 457 [280-471], P < .0001), need for invasive mechanical ventilation (IMV; 86% vs 23%, P < .0001), and mortality (28% vs 0%, P = .006) compared to those without PARDS. Forty-two percent (21/50) of patients needed IMV, of these 61% (13/21) had PARDS. Patients who needed IMV had significantly lower GCS score (8 [3-11] vs 15 [15-15], P < .0001), higher ISS score (27 [22-34] vs 18 [14-22], P = .002), longer length of stay (LOS; 7.5 [4-14] days vs 3.3 [2-5] days, P = .003), longer hospital LOS (18 [7.0-25] vs 5 [4-11], P = .008), higher PARDS rate (62% vs 7%, P < .0001), and lower S/F ratios (99 [94-190] vs 461 [353-471], P < .0001) compared to those who did not require IMV. Lower GCS score was independently associated with both PARDS and need for IMV. Conclusions: Pediatric ARDS in children with PC is independently associated with lower GCS score, and its presence significantly increased morbidity and mortality. Further larger studies are needed to explore association of lower GCS and higher injury score in children with PARDS and PC. [ABSTRACT FROM AUTHOR]

The article discusses a study on risk-stratified management to remove low-risk penicillin allergy labels in the ICU. It reports that Penicillin allergies are commonly diagnosed in childhood and go unquestioned throughout life. It mentions that these allergy diagnoses are largely inaccurate, explained instead by viral exanthems, drug–viral interactions, or nonallergic side effects.