128 research outputs found

    An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

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    Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment 1,2. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease 3. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines 4,5. We identified a whole blood 393 transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment. A subset of latent TB patients had signatures similar to those in active TB patients. We also identified a specific 86-transcript signature that discriminated active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-γ and Type I IFNαβ signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis, suggest that this TB signature reflects both changes in cellular composition and altered gene expression. Although an IFN signature was also observed in whole blood of patients with Systemic Lupus Erythematosus (SLE), their complete modular signature differed from TB with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto under-appreciated role of Type I IFNαβ signalling in TB pathogenesis, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic

    Apnea of prematurity: from cause to treatment

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    Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

    Infants Autonomic Cardio-Respiratory Responses to Nurturing Stroking Touch Delivered by the Mother or the Father

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    The building of physiological self-regulation during bonding is a crucial developmental process based on early cardio-respiratory maturation. The mother’s role as a facilitator of this physiological maturation has been evidenced and recognized in many respects. Research in fathers, however, remains sparse which may be due to the belief that bonding is a physiological behavior reserved for a mother’s maternal instinct. In the current study we compared the impact of paternal and maternal nurturing stroking touch on infants’ physiological self-regulation in terms of respiratory sinus arrhythmia (RSA). We compared the impact of a 3-min stroking period (STROKING) with a pre-baseline (PRE-STROKING) and post-baseline (POST-STROKING) of 25 mothers and 25 fathers (unrelated to one another) on their infants, aged 4–16 weeks. We registered infant electrocardiogram (ECG) and respiration to calculate infant RR-interval (RRI), respiration rate (fR) and (respiratory corrected) RSA (RSAcorr). Based on video-recordings, we analyzed the stroking speed. Infants’ RSAcorr significantly increased during and after stroking, no matter whether touch was delivered by fathers or mothers. This effect was mediated by both heart rate (HR) and respiration. However, respiratory mediation occurred later when delivered by fathers than by mothers. Both mothers’ and fathers’ stroking speed occurred within the optimal stimulation range of c-tactile (CT) afferents, a particular class of cutaneous unmyelinated, low-threshold mechano-sensitive nerves hypothesized to be involved in inter-personal bonding. The discussion builds on the idea to mitigate fathers’ doubts about their paternal capabilities and proposes a research agenda regarding the further examination of the role of nurturing touch and its underlying mechanisms within the development of infants’ physiological self-regulation. Finally, the importance of respiratory measurements in infant physiological research is emphasized

    CMS physics technical design report : Addendum on high density QCD with heavy ions

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    Dynamic touch reduces physiological arousal in preterm infants: A role for c-tactile afferents?

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    Preterm birth is a significant risk factor for a range of long-term health problems and developmental disabilities. Though touch plays a central role in many perinatal care strategies, the neurobiological basis of these approaches is seldom considered. C-Tactile afferents (CTs) are a class of unmyelinated nerve fibre activated by low force, dynamic touch. Consistent with an interoceptive function, touch specifically targeted to activate CTs activates posterior insular cortex and has been reported to reduce autonomic arousal. The present study compared the effect of 5 min of CT optimal velocity stroking touch to 5 min of static touch on the heart-rate and oxygen saturation levels of preterm infants between 28- & 37-weeks gestational age. CT touch produced a significant decrease in infants' heart-rates and increase in their blood oxygenation levels, which sustained throughout a 5-min post-touch period. In contrast, there was no significant change in heart-rate or blood oxygenation levels of infants receiving static touch. These findings provide support for the hypothesis that CTs signal the affective quality of nurturing touch, providing a neurobiological substrate for the apparent beneficial effects of neonatal tactile interventions and offering insight for their optimisation
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