Optimal duration for continuation of statin therapy in bacteremic patients.

Background: Evidence suggests statins may improve survival in patients with bloodstream infections. However, there is no consensus on optimal timing and duration of exposure.

Objectives: To quantify statin therapy duration associated with decreased mortality in bacteremic statin users.

Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocks.

Cellular heterogeneity poses a substantial challenge to understanding tissue-level phenotypes and confounds conventional bulk analyses. To analyze signaling at the single-cell level in human tissues, we applied mass cytometry using cytometry time of flight to formalin-fixed, paraffin-embedded (FFPE) normal and diseased intestinal specimens. This technique, called FFPE-DISSECT (disaggregation for intracellular signaling in single epithelial cells from tissue), is a single-cell approach to characterizing signaling states in embedded tissue samples.

Talin2-mediated traction force drives matrix degradation and cell invasion.

Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear and, indeed, talin2 has been presumed to function redundantly with talin1.

Targeting the Cytochrome bc1 Complex of Leishmania Parasites for Discovery of Novel Drugs.

Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome bc1 from Plasmodium falciparum and Toxoplasma gondii and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of Leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of Leishmania mexicana and L.

Isolation and Characterization of Escherichia coli Sequence Type 131 and Other Antimicrobial-Resistant Gram-Negative Bacilli from Clinical Stool Samples from Veterans.

Emerging multidrug-resistant (MDR) Gram-negative bacilli (GNB), including Escherichia coli sequence type 131 (ST131) and its resistance-associated H30 subclone, constitute an ever-growing public health threat. Their reservoirs and transmission pathways are incompletely defined. To assess diarrheal stools as a potential reservoir for ST131-H30 and other MDR GNB, we cultured 100 clinical stool samples from a Veterans Affairs Medical Center clinical laboratory (October to December 2011) for fluoroquinolone- and extended-spectrum cephalosporin (ESC)-resistant E.

Differences in Use of Glucose Rate of Change (ROC) Arrows to Adjust Insulin Therapy Among Individuals With Type 1 and Type 2 Diabetes Who Use Continuous Glucose Monitoring (CGM).

Objective: To understand differences between individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) in utilization of continuous glucose monitoring (CGM) data to adjust insulin therapy, either continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI).

Methods: We surveyed 300 individuals who regularly used real-time CGM, using 70 questions to obtain information about general CGM use and response to glucose rate of change (ROC) arrows.

Results: The survey was completed by 222 T1D and 78 T2D respondents treated with intensive insulin therapy.

Human plasma platelet-derived exosomes: effects of aspirin.

Platelet-derived exosomes mediate platelet atherogenic interactions with endothelial cells and monocytes. A new method for isolation of plasma platelet-derived exosomes is described and used to examine effects of aging and aspirin on exosome cargo proteins. Exosome secretion by purified platelets in vitro did not increase after exposure to thrombin or collagen, as assessed by exosome counts and quantification of the CD81 exosome marker.

Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes.

Osteoarthritis is a nonrheumatologic joint disease characterized by progressive degeneration of the cartilage extracellular matrix. Berberine (BBR) is an isoquinoline alkaloid used in traditional Chinese medicine, the majority of which is extracted from Huang Lian (Coptis chinensis). Although numerous studies have revealed the anticancer activity of BBR, its effects on normal cells, such as chondrocytes, and the molecular mechanisms underlying its actions remain elusive.

Are Research Ethics Committees Prepared for Community-Based Participatory Research?

Community-based participatory research (CBPR) is challenging to research ethics committees (RECs). We reviewed the REC preparedness when reviewing CBPR projects. We searched the MEDLINE database and included qualitative studies of CBPR researchers or REC members about their experiences with RECs.

Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo.

Understanding heterogeneous cellular behaviors in a complex tissue requires the evaluation of signaling networks at single-cell resolution. However, probing signaling in epithelial tissues using cytometry-based single-cell analysis has been confounded by the necessity of single-cell dissociation, where disrupting cell-to-cell connections inherently perturbs native cell signaling states. Here, we demonstrate a novel strategy (Disaggregation for Intracellular Signaling in Single Epithelial Cells from Tissue-DISSECT) that preserves native signaling for Cytometry Time-of-Flight (CyTOF) and fluorescent flow cytometry applications.

Selective increase in monocyte p38 mitogen-activated protein kinase activity in metabolic syndrome.

Objective: Metabolic syndrome is a common disorder that predisposes to both cardiovascular disease and diabetes. There is paucity of data on cellular signal transduction pathways in metabolic syndrome. This study determined monocyte mitogen-activated protein kinase activity in patients with metabolic syndrome.

The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development.

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that inhibits signaling by CD40 and by the receptor for B cell-activating factor (BAFF) and negatively regulates homeostatic B cell survival. Loss-of-function mutations in TRAF3 are associated with human B cell malignancies, in particular multiple myeloma. The cytokine interleukin-6 (IL-6) supports the differentiation and survival of normal and neoplastic plasma cells.

Exercise prevents development of autonomic dysregulation and hyperalgesia in a mouse model of chronic muscle pain.

Chronic musculoskeletal pain (CMP) conditions, like fibromyalgia, are associated with widespread pain and alterations in autonomic functions. Regular physical activity prevents the development of CMP and can reduce autonomic dysfunction. We tested if there were alterations in autonomic function of sedentary mice with CMP, and whether exercise reduced the autonomic dysfunction and pain induced by CMP.

Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts.

Aims: Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans.

Methods And Results: We measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study.

Sex-specific predictors of improved walking with step-monitored, home-based exercise in peripheral artery disease.

The aim of this study was to determine whether baseline clinical characteristics and the duration and intensity of ambulation during our step-monitored home-based exercise program were predictive of changes in ambulatory outcomes at completion of the program in symptomatic patients with peripheral artery disease (PAD). Twenty-two men (ankle-brachial index (ABI) = 0.71 ± 0.

Serial sampling of copeptin levels improves diagnosis and risk stratification in patients presenting with chest pain: results from the CHOPIN trial.

Background: Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combination with a negative troponin. However, management of patients with chest pain with a positive copeptin in the setting of a negative troponin is unclear.

Methods: The multicentre CHOPIN trial enrolled 2071 patients with acute chest pain.

Variation in resistance traits, phylogenetic backgrounds, and virulence genotypes among Escherichia coli clinical isolates from adjacent hospital campuses serving distinct patient populations.

Escherichia coli sequence type 13 (ST131), an emergent cause of multidrug-resistant extraintestinal infections, has important phylogenetic subsets, notably the H30 and H30Rx subclones, with distinctive resistance profiles and, possibly, clinical associations. To clarify the local prevalence of these ST131 subclones and their associations with antimicrobial resistance, ecological source, and virulence traits, we extensively characterized 233 consecutive E. coli clinical isolates (July and August 2013) from the University of Minnesota Medical Center-Fairview Infectious Diseases and Diagnostic Laboratory, Minneapolis, MN, which serves three adjacent facilities (a children's hospital and low- and high-acuity adult facilities).

An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates.

Unlabelled: The search for an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine remains a pressing need. The moderate success of the RV144 Thai clinical vaccine trial suggested that vaccine-induced HIV-1-specific antibodies can reduce the risk of HIV-1 infection. We have made several improvements to the DNA platform and have previously shown that improved DNA vaccines alone are capable of inducing both binding and neutralizing antibodies in small-animal models.

MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia.

Autologous vein grafts are commonly used for coronary and peripheral artery bypass but have a high incidence of intimal hyperplasia (IH) and failure. We present a nanopolyplex (NP) approach that efficiently delivers a mitogen-activated protein kinase (MAPK)-activated protein (MAPKAP) kinase 2 inhibitory peptide (MK2i) to graft tissue to improve long-term patency by inhibiting pathways that initiate IH. In vitro testing in human vascular smooth muscle cells revealed that formulation into MK2i-NPs increased cell internalization, endosomal escape, and intracellular half-life of MK2i.

Routine postoperative care of patients undergoing coronary artery bypass grafting on cardiopulmonary bypass.

The postoperative course of a patient undergoing cardiac surgery (CS) is dictated by a largely predictable set of interactions between disease-specific and therapeutic factors. ICU personnel need to quickly develop a detailed understanding of the patient's current status and how critical care resources can be used to promote further recovery and eventual independence from external support. The goal of this article is to describe a typical operative and postoperative course, with emphasis on the latter, and the diagnostic and therapeutic options necessary for the proper care of these patients.

Extraintestinal Pathogenic and Antimicrobial-Resistant Escherichia coli Contamination of 56 Public Restrooms in the Greater Minneapolis-St. Paul Metropolitan Area.

How extraintestinal pathogenic Escherichia coli (ExPEC) and antimicrobial-resistant E. coli disseminate through the population is undefined. We studied public restrooms for contamination with E.

Risk for broad-spectrum neuropsychiatric disorders after mild traumatic brain injury in a cohort of US Air Force personnel.

Background: Military personnel are at increased risk for traumatic brain injury (TBI) from combat and non-combat exposures. Sequelae of moderate-to-severe TBI are well described, but the literature remains conflicted regarding whether mild TBI (mTBI) results in lasting brain injury and functional impairments. This study assessed risk for a range of neuropsychiatric disorders presenting after mTBI while adjusting for the potential confounds of depression and post-traumatic stress disorder (PTSD).

Secretion of Flagellar Proteins by the Pseudomonas aeruginosa Type III Secretion-Injectisome System.

Unlabelled: The opportunistic pathogen Pseudomonas aeruginosa utilizes an injectisome-type III secretion system (injectisome-T3SS) to elicit cytotoxicity toward epithelial cells and macrophages. Macrophage killing results from the cytotoxic properties of the translocated effector proteins (ExoS, ExoT, ExoU, and ExoY) and inflammasome-mediated induction of pyroptosis. Inflammasome activation can occur following Nlrc4-mediated recognition of cytosolic translocated flagellin (FliC).

Risk factors for malaria and adverse birth outcomes in a prospective cohort of pregnant women resident in a high malaria transmission area of Papua New Guinea.

Background: Low birth weight (LBW), anaemia and malaria are common in Papua New Guinean women.

Methods: To identify risk factors for LBW, anaemia and preterm delivery (PTD), pregnant women recruited into a cohort study in Madang, Papua New Guinea, were followed to delivery.

Results: Of 470 women enrolled, delivery data were available for 328 (69.

Endothelial Cell Inflammation and Antioxidant Capacity are Associated With Exercise Performance and Microcirculation in Patients With Symptomatic Peripheral Artery Disease.

We determined whether exercise performance and lower extremity microcirculation were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in 160 patients with symptomatic peripheral artery disease (PAD). In a multivariate regression model for peak walking time, significant independent variables included ankle-brachial index (P < .001), age (P = .