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1.
Nat Commun ; 5: 4649, 2014 Aug 14.
Article in English | MEDLINE | ID: mdl-25120092

ABSTRACT

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.


Subject(s)
Bacterial Infections/immunology , Bacterial Infections/prevention & control , Immunity, Innate/physiology , Metabolic Networks and Pathways/physiology , Antigens, CD/genetics , Antigens, CD/physiology , Bacterial Infections/physiopathology , Glucose/metabolism , Homeostasis/genetics , Homeostasis/physiology , Humans , Immunity, Innate/genetics , Infant, Newborn , Leukocyte Immunoglobulin-like Receptor B1 , Lipid Metabolism/genetics , Lipid Metabolism/physiology , Metabolic Networks and Pathways/genetics , Receptors, Immunologic/genetics , Receptors, Immunologic/physiology , T-Lymphocytes/physiology
2.
Spec Care Dentist ; 22(2): 75-9, 2002.
Article in English | MEDLINE | ID: mdl-12109599

ABSTRACT

Several reports have indicated that the perception toward pain declines with age. However, since pain thresholds have been reported to be lower in females than in males, studies to detect pain perception may be more sensitive in females. In dental care, the injection of local anesthetics with a needle is used to abrogate subsequent pain from treatment. However, the anomaly of using one potentially painful procedure to prevent subsequent pain often hinders patients from seeking dental care. The purpose of this study was to evaluate the perception of pain from needle-sticks with and without anesthetic between young and elderly female subjects. We compared the perception of pain stimulated by needle-sticks without (NS) and with (NS-I) 0.3 mL of local anesthetic injected into the oral mucosal tissues of a group of 20 young females (aged 19-24 yrs) and a group of 18 elderly females (aged 70-75 yrs). A Verbal Pain Scale (VPS; descriptors assigned, 0-4) and a Visual Analogue Scale (VAS; 0-10 cm) were used to measure pain intensity. Statistical analyses by ANOVA and Fisher's Exact Test were used where appropriate. The VPS and VAS scores for perception of pain in elderly females were lower than the scores from the younger subjects. No differences between Ns and Ns-I in either age group were found. Study limitations included potential periodic hormonal imbalances in both groups of females as well as untested diminished cognitive function in elderly subjects. However, we conclude, with the noted cautions, that pain perception between the two groups was not significantly different.


Subject(s)
Anesthetics, Local/administration & dosage , Injections/adverse effects , Pain/psychology , Adult , Age Factors , Aged , Analysis of Variance , Chi-Square Distribution , Female , Humans , Mouth Mucosa , Pain/etiology , Pain Measurement , Pain Threshold , Perception , Sex Factors
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