Structural basis of substrate selectivity of E. coli prolidase.

Prolidases, metalloproteases that catalyze the cleavage of Xaa-Pro dipeptides, are conserved enzymes found in prokaryotes and eukaryotes. In humans, prolidase is crucial for the recycling of collagen. To further characterize the essential elements of this enzyme, we utilized the Escherichia coli prolidase, PepQ, which shares striking similarity with eukaryotic prolidases.

Anti-GITR agonist therapy intrinsically enhances CD8 T cell responses to chronic lymphocytic choriomeningitis virus (LCMV), thereby circumventing LCMV-induced downregulation of costimulatory GITR ligand on APC.

The costimulatory TNFR family member GITR can provide important survival signals for CD8 T cells. However, little is known about the regulation of this pathway during a chronic infection. In this study, we show that GITR ligand (GITRL) is maximally induced on APCs at day 2 post-lymphocytic choriomeningitis virus (LCMV) clone 13 infection, but is downregulated to below baseline levels by day 8 postinfection (p.

What's Past is Prologue: Relations Between Early Mathematics Knowledge and High School Achievement.

Although previous research has established the association between early-grade mathematics knowledge and later mathematics achievement, few studies have measured mathematical skills prior to school entry, nor have they investigated the predictive power of early gains in mathematics ability. The current paper relates mathematical skills measured at 54 months to adolescent mathematics achievement using multi-site longitudinal data. We find that preschool mathematics ability predicts mathematics achievement through age 15, even after accounting for early reading, cognitive skills, and family and child characteristics.

State and trait effects on individual differences in children's mathematical development.

Substantial longitudinal relations between children's early mathematics achievement and their much later mathematics achievement are firmly established. These findings are seemingly at odds with studies showing that early educational interventions have diminishing effects on children's mathematics achievement across time. We hypothesized that individual differences in children's later mathematical knowledge are more an indicator of stable, underlying characteristics related to mathematics learning throughout development than of direct effects of early mathematical competency on later mathematical competency.

Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3.

Colon cancer is a major cause of cancer-related deaths worldwide. Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer; however, it is only marginally effective in stage II patients. There is also increasing evidence that right-side colon cancer is different from left-side colon cancer.

Ischemic ventricular tachycardia presenting as a narrow complex tachycardia.

This report describes a patient presenting with a narrow complex tachycardia in the context of prior myocardial infarction and impaired ventricular function. Electrophysiological studies confirmed ventricular tachycardia and activation and entrainment mapping demonstrated a critical isthmus within an area of scar involving the His-Purkinje system accounting for the narrow QRS morphology. This very rare case shares some similarities with upper septal ventricular tachycardia seen in patients with structurally normal hearts, but to our knowledge has not been seen previously in patients with ischemic heart disease.

Final-year nursing undergraduates' understandings of palliative care: a qualitative study in Wales, UK.

Background: With worldwide population ageing and the increasing prevalence of chronic conditions, government policies promoting palliative care, and evidence of disparate or even blurred conceptions of palliative care, it is important for educators and practitioners who support undergraduate nurses to establish how these students conceptualise palliative care. Today's students are tomorrow's nurses, and their understanding will shape the ways in which palliative care is integrated into their professional practice.

Aim: The aim of this work was to explore nursing undergraduates' understandings of palliative care.

Fatal fulminant hepatic failure related to the use of disulfiram.

We report a case of fatal fulminant hepatic failure related to the use of disulfiram. This is a commonly used medication; however there are few reported cases in the medical literature of fatal liver failure related to its use. Patients using disulfiram for alcohol cessation typically have multiple risk factors for liver disease and are not acutely candidates for orthotopic liver transplant due to recent alcohol dependence.

Microscopic thymoma and parathyroid adenoma: rare combination of two distinct pathologies.

While there is an intimate anatomical and embryological relationship between the inferior parathyroid gland and thymus, concurrent pathology is rare. Three cases have been reported in the literature of a parathyroid adenoma in conjunction with a thymoma. We present a case report of a 60-year-old female with a past medical history of hypercalcemia subsequently found to have primary hyperparathyroidism.

Costimulatory TNFR family members in control of viral infection: outstanding questions.

Members of the TNFR family can play prominent roles in controlling the magnitude, duration and phenotype of the immune response to viruses. The importance of particular TNFRs in different viral infections and whether they contribute to viral control or pathology is dependent on the virus and the severity of the infection. TNFRs and their ligands are widely and differentially expressed on both adaptive and innate immune cell types.

Tensions and ambiguities: A qualitative study of final year adult field nursing students' experiences of caring for people affected by advanced dementia in Wales, UK.

Background: Rising dementia prevalence means that general nurses globally will encounter more people affected by advanced dementia. Advanced dementia care is profoundly complex yet there is a paucity of research exploring how general nursing students experience and thus learn to care for those affected.

Objectives: To explore final year nursing students' (adult field) experiences of caring for people affected by advanced dementia.

Platelets for neonatal transfusion - study 2: a randomised controlled trial to compare two different platelet count thresholds for prophylactic platelet transfusion to preterm neonates.

Introduction: Neonatal thrombocytopenia is a common and important clinical problem in preterm neonates. A trial assessing clinically relevant outcomes in relation to the different platelet count thresholds used to trigger transfusion has never been undertaken in preterm neonates with severe thrombocytopenia.

Objectives: Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in current standard practice in reducing the proportion of patients who have a major bleed or die up to study day 28.

Identification and control of a gentamicin resistant, meticillin susceptible outbreak on a neonatal unit.

We describe the identification and control of an outbreak of gentamicin resistant, meticillin susceptible (GR-MSSA) on a 36-bed neonatal unit (NNU) in London. Control measures included admission and weekly screening for GR-MSSA, cohorting affected babies, environmental and staff screening, hydrogen peroxide vapour (HPV) for terminal disinfection of cohort rooms, and reinforcement of hand hygiene. Seventeen babies were affected by the outbreak strain over ten months; seven were infected and ten were asymptomatic carriers.

The human immune system recognizes neopeptides derived from mitochondrial DNA deletions.

Mutations in mitochondrial (mt) DNA accumulate with age and can result in the generation of neopeptides. Immune surveillance of such neopeptides may allow suboptimal mitochondria to be eliminated, thereby avoiding mt-related diseases, but may also contribute to autoimmunity in susceptible individuals. To date, the direct recognition of neo-mtpeptides by the adaptive immune system has not been demonstrated.

Relationship between play and sensory processing: a systematic review.

OBJECTIVE. We examined the empirical evidence to answer the research question, What is the relationship between play and sensory processing in children ages 3-12 yr? METHOD. The PRISMA guidelines were followed to complete a systematic review.

Cell-specific and context-dependent effects of GITR in cancer, autoimmunity, and infection.

A breadth of studies have demonstrated the importance of GITR-GITRL in diverse immune processes. However, only a limited number of studies to date have attributed the effects of GITR/GITRL to specific cell types. Moreover, the context-dependent role of GITR/GITRL in different models makes the consequences of GITR ligation difficult to generalize.

Neonatal invasive fungal infection in England 2004-2010.

Rates of invasive fungal infection are highest among neonates, especially those of low birthweight. This study aimed to describe the current epidemiology of invasive neonatal fungal infections in a UK neonatal infection surveillance network. From 2004 to 2010 prospective multicentre surveillance was conducted by 14 neonatal units using a web-based database.

Eptifibatide-Induced Thrombocytopenia--When Inhibitor Turns Killer.

Eptifibatide is a commonly and widely used drug for management of acute coronary syndrome and during percutaneous coronary intervention. It is usually well tolerated with no major adverse effects. We report a rare case of life-threatening thrombocytopenia secondary to eptifibatide along with a literature review of available evidence.

Inflammation and atherosclerosis--revisited.

Atherogenesis has been traditionally viewed as a metabolic disease representing arterial obstruction by fatty deposits in its wall. Today, it is believed that atherogenesis involves highly specific biochemical and molecular responses with constant interactions between various cellular players. Despite the presence of inflammatory reaction in each and every step of atherosclerosis from its inception to terminal manifestation, the cause--effect relationship of these 2 processes remains unclear.

The media critique of the Liverpool Care Pathway: some implications for nursing education.

End-of-life care pathways are championed around the globe as tools that might be used to enhance the quality of care at the very end of a person's life. This paper examines recent negative media discourse in the UK about the Liverpool Care Pathway for the Dying Patient (LCP). This media coverage may have had damaging effects, but it has also served to highlight inappropriate and even suboptimal end-of-life care.

Accuracy of the concentration of morphine infusions prepared for patients in a neonatal intensive care unit.

Objective: To investigate the accuracy of morphine infusions prepared for neonates in relation to the label strength and to identify the differences in deviation between infusions made in neonatal intensive care unit (NICU) and those dispensed ready-to-use from pharmacy.

Methods: Unused portions of morphine solution for infusion were collected over a 6-weeks period and used to determine the concentration of the drug by high-performance liquid chromatography (HPLC).

Results: A total of 19.

GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia.

Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis.

The contextual role of TNFR family members in CD8(+) T-cell control of viral infections.

Immunity to viruses must be tightly controlled to avoid pathology. Receptors and ligands of the tumor necrosis factor (TNF) family play important roles in controlling lymphocyte activation and survival during an immune response. The role of specific TNF receptor (TNFR) family members in antiviral immunity depends on the stage of the immune response and can vary with the virus type and its virulence.

Health care reform the hourly challenge.

For those industries most likely to be transformed by the Patient Protection and Affordable Care Act (ACA), enacting the right strategy is the only strategy. A critical issue will be balancing cost and compliance factors with productivity concerns brought on by changes in the full- and part-time or hourly status of a given workforce. This article discusses industry perspectives in light of the ACA's 2014 implementation date, options for changing staffing models, and how the success of such changes depends on segmenting business units and locations while developing strategies for the different groups.

Subcutaneous emphysema and pneumolabyrinth plus pneumocephalus as complications of middle ear implant and cochlear implant surgery.

We conducted a retrospective case review at a tertiary academic medical center for the complications of pneumolabyrinth with pneumocephalus and subcutaneous emphysema after surgery for middle ear and cochlear implants. Charts of 76 cochlear implant and 2 middle ear implant patients from January 2001 through June 2009 were reviewed. We identified 1 cochlear implant recipient with pneumolabyrinth and pneumocephalus, and 1 middle ear implant recipient with subcutaneous emphysema.