Enhancing anti-tumor immunity of natural killer cells through targeting IL-15R signaling.

Interleukin-15 receptor (IL-15R) agonists induce anti-tumor immunity in pre-clinical models. However, dose-limiting toxicity has hampered their clinical development. We performed genome-wide CRISPR screens to reveal the complete IL-15R signaling mechanism in natural killer (NK) cells and discovered that ubiquitin-dependent IL-15R degradation is the dominant mechanism restraining IL-15R signaling.

Blockade of the Platelet-Driven CXCL7-CXCR1/2 Inflammatory Axis Prevents Murine Cerebral Aneurysm Formation and Rupture.

Platelet aggregation is intimately associated with vascular inflammation and is commonly seen on routine histology studies of cerebral aneurysms. Platelets, when activated, have been shown to augment neutrophil response and the pro-inflammatory cascade. Platelet-neutrophil complexes have been found to aggravate atherosclerosis through a positive feedback loop.

Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells.

The transcription factor STAT3 is activated by multiple cytokines and other extrinsic factors. It plays a key role in immune and inflammatory responses and, when dysregulated, in tumourigenesis. STAT3 is also an indispensable mediator of the cell death process that occurs during post-lactational regression of the mammary gland, one of the most dramatic examples of physiological cell death in adult mammals.

Three decades of progress from surgery to medical therapy for isolated neuroaxis V600E-positive Langerhans cell histiocytosis management: illustrative case.

Background: "Langerhans cell histiocytosis" (LCH) is a term that encompasses single-system or multisystem disorders traditionally characterized by a proliferation of clonal CD1a+/CD207+ myeloid-derived histiocytes. In most cases of LCH, mitogen-activated protein kinase (MAPK) pathway somatic mutations lead to near universal upregulation of phosphorylated extracellular signal-regulated kinase expression. The clinical manifestations of LCH are numerous, but bone involvement is common.

Highly efficient multiplex genetic engineering of porcine primary fetal fibroblasts.

Background: Genetically engineered porcine donors are a potential solution for the shortage of human organs for transplantation. Incompatibilities between humans and porcine donors are largely due to carbohydrate xenoantigens on the surface of porcine cells, provoking an immune response which leads to xenograft rejection.

Materials And Methods: Multiplex genetic knockout of GGTA1, β4GalNT2, and CMAH is predicted to increase the rate of xenograft survival, as described previously for GGTA1.

Predictors and Outcomes of Ischemic Stroke After Cardiac Surgery.

Background: Stroke is a major complication after cardiac surgery causing increased morbidity and mortality. There are limited data on outcomes of patients with large vessel occlusion after cardiac surgery.

Methods: Patients who underwent index cardiac surgeries as defined by The Society of Thoracic Surgeons (STS) from 2010 to 2017 were reviewed from a prospectively maintained database.

Evaluation of a simulation-based mini-elective on medical student interest in cardiac surgery.

Background: Integrated cardiothoracic (CT) surgery training programs are an increasingly popular pathway to train CT surgeons. Identifying and engaging medical students early is important to generate interest and ensure highly qualified applicants are aware of opportunities provided by a career in CT surgery.

Methods: An optional CT surgery "mini-elective" was developed for preclinical medical students consisting of five 2-hour sessions covering major procedures in cardiac surgery.

Late Presentation of a 9 mm Bullet in the Ureteropelvic Junction Causing Acute Renal Failure in a Solitary Functioning Left Kidney.

Urinary obstruction as a result of a late complication of a gunshot wound is rarely reported. Bullet shell fragments may migrate from their initial location into an area causing obstruction. In this study, we present a case of a left renal calculus surrounding a 9 mm gun shell in a patient with a solitary functioning left kidney.

Lung Cancer Screening Guidelines: How Readable Are Internet-Based Patient Education Resources?

Objective: Following the findings of the National Lung Screening Trial, several national societies from multiple disciplines have endorsed the use of low-dose chest CT to screen for lung cancer. Online patient education materials are an important tool to disseminate information to the general public regarding the proven health benefits of lung cancer screening. This study aims to evaluate the reading level at which these materials related to lung cancer screening are written.

An Engineered Human Adipose/Collagen Model for In Vitro Breast Cancer Cell Migration Studies.

Adipocytes are one of the major stromal cell components of the human breast. These cells play a key role in the development of the gland and are implicated in breast tumorigenesis. Frequently, directional stromal collagen I fibers are found surrounding aggressive breast tumors.

Stat3-mediated alterations in lysosomal membrane protein composition.

Lysosome function is essential in cellular homeostasis. In addition to its recycling role, the lysosome has recently been recognized as a cellular signaling hub. We have shown in mammary epithelial cells, both and , that signal transducer and activator of transcription 3 (Stat3) modulates lysosome biogenesis and can promote the release of lysosomal proteases that culminates in cell death.

Quantitative analysis of the level of readability of online emergency radiology-based patient education resources.

Purpose: The vast amount of information found on the internet, combined with its accessibility, makes it a widely utilized resource for Americans to find information pertaining to medical information. The field of radiology is no exception. In this paper, we assess the readability level of websites pertaining specifically to emergency radiology.

NFPA 99 Chapter 13 and healthcare security management.

The new NFPA 99 Security Management Standard for healthcare facilities requires a Security Vulnerability Analysis be conducted annually, the author reports. This will usually uncover little change from year to year, he says, but by using the right model the analysis can be used to win back security additions that had previously been rejected by the C-Suite.

Infectious disease protection for healthcare security officers.

Healthcare Security should be considered an active component in an infectious disease event, the authors maintain, and security officers must be included in an Employee Health screening and N95 fit testing initiative to safely welcome the incoming infected patients. In this article, they spell out the different levels of precautions officers should become familiar with in order to protect themselves.

Analysis of Perforin Assembly by Quartz Crystal Microbalance Reveals a Role for Cholesterol and Calcium-independent Membrane Binding.

Perforin is an essential component in the cytotoxic lymphocyte-mediated cell death pathway. The traditional view holds that perforin monomers assemble into pores in the target cell membrane via a calcium-dependent process and facilitate translocation of cytotoxic proteases into the cytoplasm to induce apoptosis. Although many studies have examined the structure and role of perforin, the mechanics of pore assembly and granzyme delivery remain unclear.

Development of an audiovisual speech perception app for children with autism spectrum disorders.

Perception of spoken language requires attention to acoustic as well as visible phonetic information. This article reviews the known differences in audiovisual speech perception in children with autism spectrum disorders (ASD) and specifies the need for interventions that address this construct. Elements of an audiovisual training program are described.

Assembly of streptolysin O pores assessed by quartz crystal microbalance and atomic force microscopy provides evidence for the formation of anchored but incomplete oligomers.

Streptolysin O (SLO) is a bacterial pore forming protein that is part of the cholesterol dependent cytolysin (CDC) family. We have used quartz crystal microbalance with dissipation monitoring (QCM-D) to examine SLO membrane binding and pore formation. In this system, SLO binds tightly to cholesterol-containing membranes, and assembles into partial and complete pores confirmed by atomic force microscopy.

Where there is smoke, there is fire...of a different kind.

Tackling the difficult issue of enforcing your hospital's smoke free policy, the author discusses the problems raised by smokers who just won't or can't comply. Strict enforcement, he says, is not always the best policy. The more a whole-hospital community approach is taken to truly create a "smoke free" environment, the more likely it will become uncomfortable for smokers to violate the facility's policy.

The perforin pore facilitates the delivery of cationic cargos.

Cytotoxic lymphocytes eliminate virally infected or neoplastic cells through the action of cytotoxic proteases (granzymes). The pore-forming protein perforin is essential for delivery of granzymes into the cytoplasm of target cells; however the mechanism of this delivery is incompletely understood. Perforin contains a membrane attack complex/perforin (MACPF) domain and oligomerizes to form an aqueous pore in the plasma membrane; therefore the simplest (and best supported) model suggests that granzymes passively diffuse through the perforin pore into the cytoplasm of the target cell.

Cloning and characterising an unusual perforin from chicken (Gallus gallus).

In mammals the 67 kDa pore-forming protein perforin is essential to the granule exocytosis pathway used by cytotoxic lymphocytes to eliminate virally infected and malignant cells. There is indirect evidence that this pathway exists in lower vertebrates such as teleost fish and birds, although in genome databases for the chicken and other bird species the perforin gene is incomplete and no full length expressed sequence tag has been reported. We present here the full gene and transcript sequence of chicken perforin.