Multi-Institution Analysis of Infection Control Practices Identifies the Subset Associated with Best Surgical Site Infection Performance: A Texas Alliance for Surgical Quality Collaborative Project.

Background: In an effort to reduce surgical site infection (SSI) rates, a large number of infection control practices (ICPs), including operating room attire policies, have been recommended. However, few have proven benefits and many are costly, time-consuming, and detrimental to provider morale. The goal of this multi-institution study was to determine which ICPs are associated with lower postoperative SSI rates.

Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1.

Loss of CD73-mediated extracellular adenosine production exacerbates inflammation and abnormal alveolar development in newborn mice exposed to prolonged hyperoxia.

BackgroundHyperoxic lung injury is characterized by cellular damage from high oxygen concentrations that lead to an inflammatory response and it disrupts normal alveolarization in the developing newborn lung. Adenosine is a signaling molecule that is generated extracellularly by ecto-5'-nucleotidase (CD73) in response to injury. Extracellular adenosine signals through cell surface receptors and has been found to have a protective role in acute injury situations; however, chronic elevations have been associated with detrimental changes in chronic lung diseases.

Model analysis of bidirectional interference in two-stage labeled-ligand immunoassays.

Objectives: Immunoassays involving sample incubation followed by a wash step prior to introduction of labeled analyte are potentially subject to both positive and negative interference (bidirectional interference) by a competing ligand. We examine this phenomenon from a theoretical standpoint using a mathematical model for sequential-step immunoassays in the presence of interferent.

Design & Methods: Competitive binding to antibody between analyte and interferent was modeled for sequential-step immunoassays.

MicroRNA-101 attenuates pulmonary fibrosis by inhibiting fibroblast proliferation and activation.

Aberrant proliferation and activation of lung fibroblasts contribute to the initiation and progression of idiopathic pulmonary fibrosis (IPF). However, the mechanisms responsible for the proliferation and activation of fibroblasts are not fully understood. The objective of this study was to investigate the role of miR-101 in the proliferation and activation of lung fibroblasts.

Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™).

Objectives: Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). The pathological pathways involved in fibrogenesis in IPF and interstitial lung disease associated with systemic sclerosis (SSc-ILD) show commonalities; both involve fibroblast activation, myofibroblast accumulation and deposition of extracellular matrix. The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933).

Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

Aims: Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.

Representation of Rapid Image Sequences in V4 Networks.

Natural viewing often consists of sequences of brief fixations to image patches of different structure. Whether and how briefly presented sequential stimuli are encoded in a temporal-position manner is poorly understood. Here, we performed multiple-electrode recordings in the visual cortex (area V4) of nonhuman primates (Macaca mulatta) viewing a sequence of 7 briefly flashed natural images, and measured correlations between the cue-triggered population response in the presence and absence of the stimulus.

Severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features are due to a homozygous QARS mutation.

Glutaminyl tRNA synthase is highly expressed in the developing fetal human brain. Mutations in the glutaminyl-tRNA synthetase (QARS) gene have been reported in patients with progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. We have previously reported a new recessive syndrome of severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and intellectual disability in two sisters of Ashkenazi-Jewish origin (Eur J Med Genet 2014;57(6):288-92).

Cytochrome b5 Reductase 3 Modulates Soluble Guanylate Cyclase Redox State and cGMP Signaling.

Rationale: Soluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe), is desensitized to NO and limits cGMP production needed for downstream activation of protein kinase G-dependent signaling and blood vessel dilation.

Objective: Although reactive oxygen species are known to oxidize the sGC heme iron, the basic mechanism(s) governing sGC heme iron recycling to its NO-sensitive, reduced state remain poorly understood.

Methods And Results: Oxidant challenge studies show that vascular smooth muscle cells have an intrinsic ability to reduce oxidized sGC heme iron and form protein-protein complexes between cytochrome b5 reductase 3, also known as methemoglobin reductase, and oxidized sGC.

Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.

The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer.

Beyond Cue Reactivity: Non-Drug-Related Motivationally Relevant Stimuli Are Necessary to Understand Reactivity to Drug-Related Cues.

Unlabelled: Neurobiological models of addiction posit that drug use can alter reward processes in two ways: (1) by increasing the motivational relevance of drugs and drug-related cues and (2) by reducing the motivational relevance of non-drug-related rewards. Here, we discuss the results from a series of neuroimaging studies in which we assessed the extent to which these hypotheses apply to nicotine dependence. In these studies, we recorded smokers’ and nonsmokers’ brain responses to a wide array of motivationally relevant visual stimuli that included pleasant, unpleasant, cigarette-related, and neutral images.

A Dedicated Neurological Intensive Care Unit Offers Improved Outcomes for Patients With Brain and Spine Injuries.

Background: Admission to an intensive care unit (ICU) specialized for brain and spine injury patients is associated with improved outcome. We investigated the effects of the first dedicated, combined neurological and neurosurgical ICU (NeuroICU) in Korea on patient outcomes.

Methods: The first dedicated NeuroICU in Korea was established in March 2013.

Prion-like characteristics of the bacterial protein Microcin E492.

Microcin E492 (Mcc) is a pore-forming bacteriotoxin. Mcc activity is inhibited at the stationary phase by formation of amyloid-like aggregates in the culture. Here we report that, in a similar manner as prions, Mcc naturally exists as two conformers: a β-sheet-rich, protease-resistant, aggregated, inactive form (Mcc), and a soluble, protease-sensitive, active form (Mcc).

IRE1 signaling exacerbates Alzheimer's disease pathogenesis.

Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress.

The Endoplasmic Reticulum Chaperone GRP78/BiP Modulates Prion Propagation in vitro and in vivo.

Prion diseases are fatal neurodegenerative disorders affecting several mammalian species, characterized by the accumulation of the misfolded form of the prion protein, which is followed by the induction of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). GRP78, also called BiP, is a master regulator of the UPR, reducing ER stress levels and apoptosis due to an enhancement of the cellular folding capacity. Here, we studied the role of GRP78 in prion diseases using several in vivo and in vitro approaches.

Retrospective analysis of the treatment of melasma lesions exhibiting increased vascularity with the 595-nm pulsed dye laser combined with the 1927-nm fractional low-powered diode laser.

Background: Melasma presents a significant challenge to laser surgeons. Aggressive treatments often result in rebound melasma or post-inflammatory pigmentary alteration. Recent reports suggest melasma pathogenesis may have a vascular component.

Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic.

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs), will afford important insights into the highly efficient activity of PEG-HCCs and their graphitic analogues. PEGylated perylene diimides (PEG-PDI) serve as well-defined molecular analogues of PEG-HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied.

Challenges in Laboratory Detection of Unusual Substance Abuse: Issues with Magic Mushroom, Peyote Cactus, Khat, and Solvent Abuse.

Drug abuse is a worldwide problem. Although commonly abused drugs can be identified during routine urine drug testing, less commonly abused drugs may escape detection. These less commonly abused drugs not only include some designer drugs such as synthetic cannabinoid but also include abuse of psychedelic magic mushroom (active ingredients: psilocybin and psilocin), peyote cactus (active ingredient: mescaline), and khat plants (active ingredient: cathinone).

Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (Aβ) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein.

Increased susceptibility to Aβ toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells.

Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients.

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease.

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrP) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply.