Multi-tiered proteome analysis displays the hyper-permeability of the rheumatoid synovial compartment for plasma proteins.

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining and the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the "total" proteome, the "total" IgG1 antibody repertoire and the RA-specific ACPA IgG1 autoantibody repertoire.

Substituting imported soybean meal with locally produced novel yeast protein in concentrates for Norwegian Red dairy cows: implications for rumen microbiota and fatty acid composition.

This research paper addresses the hypothesis that substituting soybean meal with locally produced yeast protein from in barley-based concentrates for Norwegian Red (NR) dairy cows does not have adverse effects on milk fatty acid (FA) composition, rumen microbiota and sensory quality of milk. As soybeans also represent valuable protein sources for human consumption, alternative protein sources need to be investigated for animal feed. A total of 48 NR dairy cows were allocated into three feeding treatments, with the same basal diet of grass silage, but different concentrates.

Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis.

The presence of autoantibodies is a defining feature of many autoimmune diseases. The number of unique autoantibody clones is conceivably limited by immune tolerance mechanisms, but unknown due to limitations of the currently applied technologies. Here, we introduce an autoantigen-specific liquid chromatography-mass spectrometry-based IgG1 Fab profiling approach using the anti-citrullinated protein antibody (ACPA) repertoire in rheumatoid arthritis (RA) as an example.

A robust nanoscale RP HPLC-MS approach for sensitive Fc proteoform profiling of IgG allotypes.

The conserved region (Fc) of IgG antibodies dictates the interactions with designated receptors thus defining the immunological effector functions of IgG. Amino acid sequence variations in the Fc, recognized as subclasses and allotypes, as well as post-translational modifications (PTMs) modulate these interactions. Yet, the high similarity of Fc sequences hinders allotype-specific PTM analysis by state-of-the-art bottom-up methods and current subunit approaches lack sensitivity and face co-elution of near-isobaric allotypes.

lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.

Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs may play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation.

Author Correction: Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus.

The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of α-D-isoglutamic acid in position 2 of the stem peptide plays a decisive role in the polymerization of cell wall building blocks. S.

Restricted immune activation and internalisation of anti-idiotype complexes between drug and antidrug antibodies.

Objectives: Therapeutic antibodies can provoke an antidrug antibody (ADA) response, which can form soluble immune complexes with the drug in potentially high amounts. Nevertheless, ADA-associated adverse events are usually rare, although with notable exceptions including infliximab. The immune activating effects and the eventual fate of these 'anti-idiotype' complexes are poorly studied, hampering assessment of ADA-associated risk of adverse events.

A Trickster in Disguise: Hyaluronan's Ambivalent Roles in the Matrix.

Hyaluronan (HA) is a simple but diverse glycosaminoglycan. It plays a major role in aging, cellular senescence, cancer, and tissue homeostasis. In which way HA affects the surrounding tissues greatly depends on the molecular weight of HA.

lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.

A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease.

Adult Outcomes After Newborn Respiratory Failure Treated With Extracorporeal Membrane Oxygenation.

Objective: To describe the outcome of young adults treated for hypoxemic respiratory failure with extracorporeal membrane oxygenation as neonates.

Design: The study was designed as a multisite, cross sectional survey.

Setting: The survey was completed electronically or on paper by subjects and stored in a secure data base.

Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: neurodevelopmental follow-up.

Objective: To report the neurodevelopmental outcome of infants enrolled in a randomized multicenter trial of early inhaled nitric oxide (iNO) in term and near-term neonates with hypoxic respiratory failure and pulmonary hypertension.

Study Design: Neonates born at > or = 34 weeks gestation who required assisted ventilation and had an oxygenation index > or = 15 and < 25 were randomized to an early iNO group or a control group. A comprehensive neurodevelopmental assessment of survivors was performed at age 18 to 24 months.

Predicting outcome in neonatal hypoxic respiratory failure with the score for neonatal acute physiology (SNAP) and highest oxygen index (OI) in the first 24 hours of admission.

Objective: To determine the clinical utility of SNAP score versus the highest oxygen index (OI) in first 24 hours of admission in predicting outcome of HRF.

Study Design: All admissions (1991 to 1999) > or =36 weeks gestation, ventilated for > or =12 hours with FiO(2)> or =0.50, without congenital anomalies were reviewed.

A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure.

Objective: Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence of death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration of iNO earlier in respiratory failure results in additional reduction in the incidence of these outcomes.

Methods: Neonates who were born at > or =34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) > or =15 and <25 on any 2 measurements in a 12-hour interval.

Return to treatment after assessment in a community children's mental health clinic.

Most people who receive mental health assessments do not follow up on needed treatment. The authors examined factors that predicted return for at least one treatment visit among 113 children who presented for treatment at a rural community mental health center, using predictors of return for adults from a previous study. Sixty-four percent of the children, compared with 46 percent of the adults, returned at least once.

Monitoring and enforcing cultural competence in Medicaid managed behavioral health care.

In recent years cultural competence has expanded beyond language provisions to include understanding and factoring into services provision the cultural perspectives clients may have that are different from the majority culture. The federal government requires state Medicaid programs to offer culturally competent services, but little is known about how states implement such mandates and monitor and enforce them. We reviewed the origins and implications of cultural competence mandates and conducted a brief case study of 5 states to learn about the implementation of cultural competence provisions in behavioral managed care contracts.

Persistent pulmonary hypertension of the newborn. Rational therapy based on pathophysiology.

Persistent pulmonary hypertension of the newborn is a common disorder among near-term gestation newborns. Persistent pulmonary hypertension of the newborn is characterized by hypoxemia that is frequently refractory to conventional management. This article describes the pathophysiologic basis of the disorder and the current therapy that is based on this knowledge.

Prospective diagnosis of alveolar capillary dysplasia in infants with congenital heart disease.

Alveolar capillary dysplasia (ACD) is a lethal pulmonary disorder found in newborns that is characterized by severe pulmonary hypertension and hypoxemia. We report on the clinical behavior of this disorder in a series of patients and its association with congenital heart disease, especially left heart obstructive disease; we also report a prospective diagnosis of ACD by lung biopsy in a newborn with congenital heart disease, which prevented futile and prolonged medical intervention.

Pulmonary hemorrhage: clinical course and outcomes among very low-birth-weight infants.

Objective: To describe the clinical course, neonatal morbidity, and neurodevelopmental outcomes of very low-birth-weight (<1500 g) children who develop pulmonary hemorrhage.

Design: A retrospective case-control study in which 58 very low-birth-weight infants who developed pulmonary hemorrhage during 1990 through 1994, of whom 29 survived, were each matched to the next admitted infant who required mechanical ventilation for respiratory distress syndrome and was of the same sex, race, and birth weight (within 250 g).

Setting: A regional tertiary neonatal intensive care unit and follow-up clinic for high-risk infants at University Hospitals of Cleveland, Cleveland, Ohio.

Effect of exogenous and endogenous nitric oxide on the airway and tissue components of lung resistance in the newborn piglet.

Despite widespread reports of the vasodilatory actions of nitric oxide (NO), little is known of the relaxant effect of NO on newborn airways or lung parenchymal structures. We studied the effects of inhaled NO at 20, 40, and 80 ppm on lung (Rl), tissue (Rti), and airway (R(aw)) resistance in 13 2-5-d-old anesthetized, ventilated, open-chested piglets. Rl was measured from transpulmonary pressure and air flow.

Severe respiratory failure in neonates: mortality and morbidity rates and neurodevelopmental outcomes.

Objective: To compare the survival, neurodevelopmental, and health outcomes of children with severe respiratory illness treated with and without extracorporeal membrane oxygenation (ECMO).

Design: Prospective collection of clinical and demographic data of all neonates reaching illness severity criteria, with follow-up at 8 and 20 months of age. Patients were assigned to treatment by the attending physician.

The natural history of direct hyperbilirubinemia associated with extracorporeal membrane oxygenation.

Objective: To determine the incidence and natural history of direct hyperbilirubinemia in neonates treated with extracorporeal membrane oxygenation.

Design: A prospective series of patients.

Setting: A level 3 neonatal intensive care unit and center for extracorporeal membrane oxygenation in Ohio.

Carotid reconstruction in the neonate following ECMO.

Permanent ligation of the carotid artery remains a major objection to the use of extra corporeal membrane oxygenation (ECMO) in infants with severe cardiorespiratory disorders. Because reconstruction of the carotid artery is highly desirable, we began a study to evaluate the feasibility and risks of carotid artery repair following decannulation. All infants placed on ECMO from December 1988 to January 1990 were evaluated for carotid artery reconstruction.