Incremental balloon deflation following complete resuscitative endovascular balloon occlusion of the aorta results in steep inflection of flow and rapid reperfusion in a large animal model of hemorrhagic shock.

Introduction: To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines.

Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.

The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian-human immunodeficiency virus (SHIV) challenge.

Paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell (HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic mutations in PIGA (which encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors.

Carotid Bulb Webs as a Cause of "Cryptogenic" Ischemic Stroke.

Background And Purpose: Carotid webs are intraluminal shelf-like filling defects at the carotid bulb with recently recognized implications in patients with recurrent ischemic stroke. We sought to determine whether carotid webs are an under-recognized cause of "cryptogenic" ischemic stroke and to estimate their prevalence in the general population.

Materials And Methods: A retrospective review of neck CTA studies in young patients with cryptogenic stroke over the past 6 years ( = 33) was performed to determine the prevalence of carotid webs compared with a control group of patients who received neck CTA studies for reasons other than ischemic stroke ( = 63).

Asymptomatic carotid stenosis: Medicine alone or combined with carotid revascularization.

Two positive randomized trials established carotid endarterectomy (CEA) as a superior treatment to medical management alone for the treatment of asymptomatic carotid artery stenosis. However, advances in medical therapy have led to an active and spirited debate about the best treatment for asymptomatic carotid stenosis. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST 2) trial aims to better define the best treatment for the average patient with severe asymptomatic carotid stenosis.

Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment.

Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability.

Small changes, big effects: The hemodynamics of partial and complete aortic occlusion to inform next generation resuscitation techniques and technologies.

Background: The transition from complete aortic occlusion during resuscitative endovascular balloon occlusion of the aorta can be associated with hemodynamic instability. Technique refinements and new technologies have been proposed to minimize this effect. In order to inform new techniques and technology, we examined the relationship between blood pressure and aortic flow during the restoration of systemic circulation following aortic occlusion at progressive levels of hemorrhage.

Development of a preoperative predictive model for major complications following adult spinal deformity surgery.

OBJECTIVE The operative management of patients with adult spinal deformity (ASD) has a high complication rate and it remains unknown whether baseline patient characteristics and surgical variables can predict early complications (intraoperative and perioperative [within 6 weeks]). The development of an accurate preoperative predictive model can aid in patient counseling, shared decision making, and improved surgical planning. The purpose of this study was to develop a model based on baseline demographic, radiographic, and surgical factors that can predict if patients will sustain an intraoperative or perioperative major complication.

A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG-ACRIN Cancer Research Group (E2607).

Background: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11 . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes.

Automated variable aortic control versus complete aortic occlusion in a swine model of hemorrhage.

Background: Future endovascular hemorrhage control devices will require features that mitigate the adverse effects of vessel occlusion. Permissive regional hypoperfusion (PRH) with variable aortic control (VAC) is a novel strategy to minimize hemorrhage and reduce the ischemic burden of complete aortic occlusion (AO). The objective of this study was to compare PRH with VAC to AO in a lethal model of hemorrhage.

Effective implementation of novel MET pharmacodynamic assays in translational studies.

MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies.

Coronary Plaque Progression and Regression in Asymptomatic African American Chronic Cocaine Users With Obstructive Coronary Stenoses: A Preliminary Study.

Objective: Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a 12-month period was associated with coronary plaque regression in cocaine users.

Methods: Fifteen African American chronic cocaine users with previously coronary computed tomography angiography (CCTA)-confirmed >50% coronary stenosis in Baltimore, Maryland, were enrolled in a study to investigate whether reduced cocaine use is associated with changes in coronary plaque burden over a 12-month period of cash-based incentive intervention, which was implemented to systematically reinforce cocaine abstinence.

Low p16 Expression in Early Passage Human Prostate Basal Epithelial Cells Enables Immortalization by Telomerase Expression Alone.

Background: There are two principal senescence barriers that must be overcome to successfully immortalize primary human epithelial cells in culture, stress-induced senescence, and replicative senescence. The p16 /retinoblastoma protein (p16/Rb) pathway mediates stress-induced senescence, and is generally upregulated by primary epithelial cells in response to the artificial conditions from tissue culture. Replicative senescence is associated with telomere loss.

Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis.

Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.

Design And Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies.

Direct-site endovascular repair (DSER): A novel approach to vascular trauma.

Peripheral vascular injuries carry significant risk for permanent functional impairment, limb loss, and death. Definitive correction of these injuries requires significant operative time and has traditionally been resource and skill set intensive. In the initial surgical treatment of the physiologically depleted trauma patient, faster techniques may prove more appropriate.

Anxiolytic Actions of Exercise in Absence of New Neurons.

Physical exercise reduces anxiety-like behavior in adult mice. The specific mechanisms that mediate this anxiolytic effect are unclear, but adult neurogenesis in the dentate gyrus has been implicated because it is robustly increased by running and has been linked to anxiodepressive-like behavior. We therefore tested the effects of long-term wheel running on anxiety-like behavior in GFAP-TK (TK) mice, a transgenic strain with complete ablation of adult neurogenesis.

Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+).

Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis.

Unlabelled: Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies.

Nucleus accumbens dopamine D2-receptor expressing neurons control behavioral flexibility in a place discrimination task in the IntelliCage.

Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated group-housing experimental cage apparatus, in combination with a reversible neurotransmission blocking technique to examine the role of NAc D1- and D2-MSNs in the acquisition and reversal learning of a place discrimination task.

Cardiovascular Disease and 10-Year Mortality in Postmenopausal Women with Clinical Features of Polycystic Ovary Syndrome.

Background: Women with polycystic ovary syndrome (PCOS) have greater cardiac risk factor clustering but the link with mortality is incompletely described.

Objective: To evaluate outcomes in 295 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS.

Materials And Methods: A total of 25/295 (8%) women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia, defined as the top quartile of androstenedione (≥701 pg/mL), testosterone (≥30.

A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis.

The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells.