https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens. It is a multi-system disease, and patients can present in vastly different ways. Prevalence varies with ethnicity, but is estimated to be about 1 per 1000 overall with a female to male ratio of 10:1. The clinical heterogeneity of this disease mirrors its complex aetiopathogenesis, which highlights the importance of genetic factors and individual susceptibility to environmental factors. SLE can affect every organ in the body. The most common manifestations include rash, arthritis and fatigue. At the more severe end of the spectrum, SLE can cause nephritis, neurological problems, anaemia and thrombocytopaenia. Over 90% of patients with SLE have positive anti-nuclear antibodies (ANA). Significant titres are accepted to be of 1:80 or greater. SLE is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life-threatening, but often incapacitating day to day symptoms. Hydroxychloroquine and non-steroidal anti-inflammatory drugs are used for milder disease; corticosteroids and immunosuppressive therapies are generally reserved for major organ involvement; anti-CD20 monoclonal antibody is now used in patients with severe disease who has not responded to conventional treatments. Despite enormous improvements in prognosis since the introduction of corticosteroids and immunosuppressive drugs, SLE continues to have a significant impact on the mortality and morbidity of those affected.

/pdf/systemic-lupus-erythematosus-34b38trluu.pdf

Systemic lupus erythematosus

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy

The emerging diversity of single-cell RNA-seq datasets allows for the full transcriptional characterization of cell types across a wide variety of biological and clinical conditions. However, it is challenging to analyze them together, particularly when datasets are assayed with different technologies, because biological and technical differences are interspersed. We present Harmony (
 https://github.com/immunogenomics/harmony
 ), an algorithm that projects cells into a shared embedding in which cells group by cell type rather than dataset-specific conditions. Harmony simultaneously accounts for multiple experimental and biological factors. In six analyses, we demonstrate the superior performance of Harmony to previously published algorithms while requiring fewer computational resources. Harmony enables the integration of ~106 cells on a personal computer. We apply Harmony to peripheral blood mononuclear cells from datasets with large experimental differences, five studies of pancreatic islet cells, mouse embryogenesis datasets and the integration of scRNA-seq with spatial transcriptomics data. Harmony, for the integration of single-cell transcriptomic data, identifies broad and fine-grained populations, scales to large datasets, and can integrate sequencing- and imaging-based data.

/pdf/fast-sensitive-and-accurate-integration-of-single-cell-data-28gd0w4ige.pdf

Fast, sensitive and accurate integration of single-cell data with Harmony.

https://cdr.lib.unc.edu/downloads/9p290c48k

ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery)

Nitric oxide provokes vasodilation and inhibits platelet aggregation. We examined the effect of nitric oxide on superoxide anion production by three sources: activated intact neutrophils, xanthine oxidase/hypoxanthine, and the NADPH oxidase. Nitric oxide significantly inhibited the generation of superoxide anion by neutrophils exposed to either FMLP (10(-7)M) or PMA (150 ng/ml) (IC50 = 30 microM). To determine whether the effect of nitric oxide on the respiratory burst was due to simple scavenging of O2+, kinetic studies that compared effects on neutrophils and the cell-free xanthine oxidase system were performed. Nitric oxide inhibited O2+ produced by xanthine oxidase only when added simultaneously with substrate, consistent with the short half-life of NO in oxygenated solution. In contrast, the addition of nitric oxide to neutrophils 20 min before FMLP resulted in the inhibition of O2+ production, which suggests formation of a stable intermediate. The effect of nitric oxide on the cell-free NADPH oxidase superoxide-generating system was also examined: The addition of NO before arachidonate activation (t = -6 min) significantly inhibited superoxide anion production. Nitric oxide did not inhibit O2+ when added at NADPH initiation (t = 0). Treatment of the membrane but not cytosolic component of the oxidase was sufficient to inhibit O2+ generation. The data suggest that nitric oxide inhibits neutrophil O2+ production via direct effects on membrane components of the NADPH oxidase. This action must occur before the assembly of the activated complex.

/pdf/nitric-oxide-an-endothelial-cell-relaxation-factor-inhibits-2gfkhr5ar2.pdf

Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase.

Brain maturation is delayed in infants with complex congenital heart defects

Background Neuorological deficits are observed in patients with congenital heart disease (CHD) before and after neonatal surgery, the etiology being multifactorial. To understand the impact of preoperative events and to characterize the evaluation of neurological injury, we performed serial magnetic resonance imaging (MRI) studies of the brain in a cohort of neonates undergoing open-heart surgery. Methods and Results Twenty-four term neonates with CHD were studied prospectively with brain MRI: before surgery, within 2 weeks of surgery, and several months after surgery. Preoperative MRI examinations showed periventricular leukomalacia (PVL) in 4 patients (16%) and infarct in 2 subjects (8%). MR spectroscopy was performed in 19 subjects preoperatively and revealed elevated brain lactate in 53%. An early postoperative MRI (n=21) identified new PVL in 48%, new infarct in 19%, and new parenchymal hemorrhage in 33%. New lesions or worsening of preoperative lesions occurred in 67% of subjects. No patient- or pro...

An MRI study of neurological injury before and after congenital heart surgery.

OBJECTIVES The purposes of this study are to describe the quality of life and cognitive function in school-aged children who have undergone staged palliation for hypoplastic left heart syndrome (HLHS), and to identify factors that are predictive of neurodevelopmental outcome in this population. METHODS School-aged survivors with HLHS who had undergone palliative surgery at our institution were identified and mailed a questionnaire to assess subjectively quality of life, school performance, and incidence of medical complications. A subgroup of local patients underwent standardized testing of cognitive function and neurologic examination. These patients were compared with the larger (remote) group of questionnaire respondents to determine whether results may be generalizable to the entire HLHS population. Potential predictors of neurologic and cognitive outcome were tested for their association with test scores using multivariate regression analysis. RESULTS Questionnaire results were obtained from 115 of 138 eligible children (83%; mean age: 9.0 +/- 2.0 years). Standardized testing was performed in 28 of 34 (82%) eligible local patients (mean age: 8.6 +/- 2.1 years). The majority of parents or guardians described their child's health as good (34%) or excellent (45%) and their academic performance as average (42%) or above average (42%). One third of the children, however, were receiving some form of special education. Chronic medication usage was common (64%); the incidence of medical complications was comparable to that previously reported in children with Fontan physiology. Cognitive testing of the local group demonstrated a median full scale IQ of 86 (range: 50-116). Mental retardation (IQ: <70) was noted in 18% of patients. In multivariate analysis, only the occurrence of preoperative seizures predicted lower full scale IQ. CONCLUSIONS Although the majority of school-aged children with HLHS had IQ scores within the normal range, mean performance for this historical cohort of survivors was lower than that in the general population.

Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28199807%2941%3A7%3C1141%3A%3AAID-ART2%3E3.0.CO%3B2-S

Robert R. Clancy

Papers

Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase.

Brain maturation is delayed in infants with complex congenital heart defects

An MRI study of neurological injury before and after congenital heart surgery.

Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome.

The role of nitric oxide in inflammation and immunity