CT-guided microwave ablation of renal cell carcinoma in a horseshoe kidney.

Renal fusion anomalies are rare congenital malformations that comprise horseshoe kidney and crossed fused ectopia. Renal tumors arising from these fusion anomalies are anatomically complex, and surgical management can be technically challenging because of altered renal anatomy. Percutaneous CT-guided ablation can overcome some of these anatomical constraints, and microwave ablation has the additional benefit of shorter treatment time and reduced sensitivity to heat sink effects compared to other ablative modalities.

IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma.

Multiple Myeloma (MM) is a plasma cell neoplasm originating in the bone marrow and is the second most common blood cancer in the United States. One challenge in understanding the pathogenesis of MM and improving treatment is a lack of immunocompetent mouse models. We previously developed the IL6Myc mouse that generates plasmacytomas at 100% penetrance that phenotypically resemble aggressive MM.

Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: a population-based interrupted time-series analysis.

Objectives: To determine the impact of the introduction of biologic DMARDs (bDMARDs) on severe infections among people newly diagnosed with RA compared with non-RA individuals.

Methods: In this population-based retrospective cohort study using administrative data (from 1990-2015) for British Columbia, Canada, all incident RA patients diagnosed between 1995 and 2007 were identified. General population controls with no inflammatory arthritis were matched to RA patients based on age and gender, and were assigned the diagnosis date (i.

Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy.

Background: Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood.

Objectives: The study's objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients.

Has the incidence of total joint arthroplasty in rheumatoid arthritis decreased in the era of biologics use? A population-based cohort study.

Objectives: To determine whether the introduction of biological DMARDs (bDMARDs) was associated with reduced incidences of total hip and knee arthroplasty (THA/TKA) among patients with RA compared with OA.

Methods: Using a population-based cohort in British Columbia, Canada, RA and OA patients diagnosed between 1995 and 2007 were divided into semi-annual cohorts according to diagnosis date. For each cohort, we calculated 8-year incidence rates of THA and TKA.

Structure-Based Design of Selective LONP1 Inhibitors for Probing Biology.

LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression of LONP1 promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Despite the importance of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature.

MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty.

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC).

Effortful control moderates the relation between negative emotionality and socially appropriate behavior.

The current study investigated the relation between negative emotionality and socially appropriate behavior in a diverse sample of preschool and kindergarten children (N = 74). More specifically, we tested whether effortful control would moderate this relation. A computerized task measured children's effortful control by assessing their accuracy in shifting attention between different emotionally valenced faces (happy and angry) while inhibiting their responses to neutral faces.

Kras-Deficient T Cells Attenuate Graft-versus-Host Disease but Retain Graft-versus-Leukemia Activity.

Acute graft-versus-host disease (aGVHD) is one major serious complication that is induced by alloreactive donor T cells recognizing host Ags and limits the success of allogeneic hematopoietic stem cell transplantation. In the current studies, we identified a critical role of Kras in regulating alloreactive T cell function during aGVHD. Kras deletion in donor T cells dramatically reduced aGVHD mortality and severity in an MHC-mismatched allogeneic hematopoietic stem cell transplantation mouse model but largely maintained the antitumor capacity.

The management of the poisoned patient using a novel emergency department-based resuscitation and critical care unit (ResCCU).

Objectives: The Resuscitation & Critical Care Unit (ResCCU) is a novel ED-based ICU designed to provide early critical care services. This study sought to identify characteristics of poisoned patients treated in the ResCCU.

Methods: We conducted a retrospective, single-center case study of poisoned patients over the age of 18 years old over a 16-month period.

Signaling through the type 2 cannabinoid receptor regulates the severity of acute and chronic graft-versus-host disease.

Graft-versus-host disease (GVHD) pathophysiology is a complex interplay between cells that comprise the adaptive and innate arms of the immune system. Effective prophylactic strategies are therefore contingent upon approaches that address contributions from both immune cell compartments. In the current study, we examined the role of the type 2 cannabinoid receptor (CB2R), which is expressed on nearly all immune cells, and demonstrated that absence of the CB2R on donor CD4+ or CD8+ T cells or administration of a selective CB2R pharmacological antagonist exacerbated acute GVHD lethality.

Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix-integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in nonmalignant, nonmotile epithelial cells is not well understood.

MRI Insights Into Adolescent Neurocircuitry-A Vision for the Future.

Adolescence is the time of onset of many psychiatric disorders. Half of pediatric patients present with comorbid psychiatric disorders that complicate both their medical and psychiatric care. Currently, diagnosis and treatment decisions are based on symptoms.

Severe Impairment of Microcirculatory Perfused Vessel Density Is Associated With Postoperative Lactate and Acute Organ Injury After Cardiac Surgery.

Objective: Resuscitation after cardiac surgery needs to address multiple pathophysiological processes that are associated with significant morbidity and mortality. Functional microcirculatory derangements despite normal systemic hemodynamics have been previously described but must be tied to clinical outcomes. The authors hypothesized that microcirculatory dysfunction after cardiac surgery would include impaired capillary blood flow and impaired diffusive capacity and that subjects with the lowest quartile of perfused vessel density would have an increased postoperative lactate level and acute organ injury scores.

Pathogenic Bhlhe40+ GM-CSF+ CD4+ T cells promote indirect alloantigen presentation in the GI tract during GVHD.

Gastrointestinal (GI) tract involvement is the major cause of morbidity and mortality in acute graft-versus-host disease (GVHD), and pathological damage is largely attributable to inflammatory cytokine production. Recently, granulocyte-macrophage colony stimulating factor (GM-CSF) has been identified as a cytokine that mediates inflammation in the GI tract, but the transcriptional program that governs GM-CSF production and the mechanism by which GM-CSF links adaptive to innate immunity within this tissue site have not been defined. In the current study, we identified Bhlhe40 as a key transcriptional regulator that governs GM-CSF production by CD4+ T cells and mediates pathological damage in the GI tract during GVHD.

Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals.

A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals.

Predictors of Short Intensive Care Unit Stay for Patients with Diabetic Ketoacidosis Using a Novel Emergency Department-Based Resuscitation and Critical Care Unit.

Background: The resuscitation and critical care unit is a novel emergency department-intensive care unit designed to provide early critical care to emergency department patients for ≤24 h.

Objectives: This study sought to identify clinical variables associated with short intensive care unit (ICU) stays in patients with diabetic ketoacidosis (DKA), who commonly require ICU-level care.

Methods: We conducted a retrospective, single-center, cross-sectional study of DKA patients ≥18 years of age who presented to an academic, urban hospital emergency department over 16 months.

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

Background: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care.

Methods: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries.

Bim regulates the survival and suppressive capability of CD8 FOXP3 regulatory T cells during murine GVHD.

CD8 Foxp3 T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4 Fox3 T cells have not been well delineated. Using an experimental model of graft-versus-host disease (GVHD), we observed that CD8 Tregs were significantly less potent than CD4 Tregs for the suppression of GVHD. To define the mechanistic basis for this observation, we examined the T-cell repertoire and the transcriptional profile of in vivo-derived CD4 and CD8 Tregs that emerged early during this disease.

An exploratory longitudinal study of social and language outcomes in children with autism in bilingual home environments.

Little is known about outcomes of early intervention for children with autism spectrum disorder reared in bilingual homes. There are concerns that social communication deficits among children with autism spectrum disorder may reduce the developmental benefits of early intervention for children with autism spectrum disorder raised in bilingual environments. We conducted an exploratory analysis of cross-sectional and longitudinal data from a larger study to explore associations between home language environment and language ability and social skills in response to early autism spectrum disorder intervention.

Host interleukin 6 production regulates inflammation but not tryptophan metabolism in the brain during murine GVHD.

Graft-versus-host disease (GVHD) induces pathological damage in peripheral target organs leading to well-characterized, organ-specific clinical manifestations. Patients with GVHD, however, can also have behavioral alterations that affect overall cognitive function, but the extent to which GVHD alters inflammatory and biochemical pathways in the brain remain poorly understood. In the current study, we employed complementary murine GVHD models to demonstrate that alloreactive donor T cells accumulate in the brain and affect a proinflammatory cytokine milieu that is associated with specific behavioral abnormalities.