Near-infrared spectroscopic indices for unresolved stellar populations: I. Template galaxy spectra

Context. A new generation of spectral synthesis models has been developed in recent years, but there is no matching set of template galaxy spectra, in terms of quality and resolution, for testing and refining the new models. Aims: Our main goal is to find and calibrate new near-infrared spectral indices along the Hubble sequence of galaxies which will be used to obtain additional constraints to the population analysis based on medium-resolution integrated spectra of galaxies. Methods: Spectra of previously studied and well-understood galaxies with relatively simple stellar populations (e.g., ellipticals or bulge dominated galaxies) are needed to provide a baseline data set for spectral synthesis models. Results: X-shooter spectra spanning the optical and infrared wavelengths (350-2400 nm) of bright nearby elliptical galaxies with a resolving power of R \u2dc 4000-5400 were obtained. Heliocentric systemic velocity, velocity dispersion, and Mg, Fe, and H\u3b2 line-strength indices are presented. Conclusions: We present a library of very-high-quality spectra of galaxies covering a large range of age, metallicity, and morphological type. Such a dataset of spectra will be crucial to addressing important questions of the modern investigation concerning galaxy formation and evolution

Respiratory syncytial virus (RSV) bronchiolitis : clinical and immunological determinants of short-term and long-term airway morbidity

Respiratory syncytial virus (RSV) infection is the most frequent cause of lower respiratory tract infection (LRTI) during infancy. During the winter season RSV bronchiolitis is one the most common causes of hospitalization as well as mechanical ventilation (MV). Following RSV bronchiolitis 30-70% infants develop recurrent episodes of wheezing. The aim of this thesis was to study clinical and immunological predictors of short-term and long-term airway morbidity. New predictors will be useful in the clinical setting as well as understanding mechanisms underlying RSV bronchiolitis and the development of subsequent airway morbidity. Post-conceptional age in mechanically ventilated infants - New strategies have become available to prevent severe RSV infection in prematurely born infants, including palivizumab, a humanized monoclonal antibody. It is not known for how long prevention of RSV infection in preterm infants should be considered. It was shown that preterm infants, without chronic lung disease have increased risk for severe RSV infection until post-conceptional age reaches 44 weeks. Cell-mediated immunity to RSV - We compared the immune response in the blood and nasopharyngeal aspirates between RSV-infected infants with and without the requirement of MV. In vivo IFN-? levels in the nasopharynx were lower in RSV-infected infants requiring MV. In addition, we have shown that monocyte interleukin (IL)-12 production was inversely related to duration of MV. Taken together, these data suggest that severe RSV LRTI is associated with decreased level of CMI and that initiation of CMI is required for the convalescence of MV during RSV LRTI. Prediction of long-term airway morbidity - Studies in the past have shown that clinical parameters, such as sex, age at onset of RSV LRTI and disease severity during RSV LRTI are not related to long term airway morbidity. We demonstrate that airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing. Monocyte IL-10 production and long-term airway morbidity We have shown that monocyte IL-10 production in the blood during the convalescent phase of RSV LRTI predicts subsequent recurrent wheezing. This is one of the major findings presented in this thesis. Conclusion This thesis has provided new determinants of short-term and long-term airway morbidity associated with RSV LRTI. Findings lead to the conclusion that antigen-presenting cells (APC) could play an orchestrating role in the immune response during RSV bronchiolitis. Therefore, we conclude that future research should focus on the role of APC, including dendritic cells, in the pathogenesis in RSV LRTI

Prevalence of human respiratory syncytial virus circulating in Iran

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and is associated with a great burden on patients, parents, and society. While no treatment is yet available, results from recent phase 2 clinical trials of cell-entry inhibitors and RSV vaccines are promising. To prepare for introduction of these novel therapeutics, good understanding of its molecular epidemiology and continuous RSV surveillance data are necessary. This paper provides an overview of RSV prevalence and genotype distribution in Iran from 1996 to 2013. This meta-analysis includes 21 published studies. In total, 775 (18.7) of 4140 respiratory specimens were positive for RSV infection. The male-female ratio of RSV-positive patients was 1.5:1. Significant peaks of RSV infection were detected during the cold season (November-March). RSV infection was mainly observed in patients <2 years of age. Phylogenetic studies showed that genotypes GA1, GA2, GA5, and BA co-circulated in Iran in 2007-2013. This review highlights the necessity of introducing standard molecular surveillance programs to inform the epidemiological, clinical, and pathological characteristics of various RSV genotypes. Improved understanding of the molecular epidemiology will be useful for development of novel RSV therapeutics. © 2015 King Saud Bin Abdulaziz University for Health Sciences

Opioids and viral infections: A double-edged sword

Opioids and their receptors have received remarkable attention because they have the ability to alter immune function, which affects disease progression. In vitro and in vivo findings as well as observations in humans indicate that opioids and their receptors positively or negatively affect viral replication and virus-mediated pathology. The present study reviews recent insights in the role of opioids and their receptors in viral infections and discusses possible therapeutic opportunities. This review supports the emerging concept that opioids and their receptors have both favorable and unfavorable effects on viral disease, depending on the type of virus. Targeting of the opioid system is a potential option for developing effective therapies; however caution is required in relation to the beneficial functions of opioid systems. © 2016 Tahamtan, Tavakoli-Yaraki, Mokhtari-Azad, Teymoori-Rad, Bont, Shokri and Salimi

Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity

Drug-induced liver injury (DILI) is an important problem both in the clinic and in the development of new safer medicines. Two pivotal adaptation and survival responses to adverse drug reactions are oxidative stress and cytokine signaling based on the activation of the transcription factors Nrf2 and NF-κB, respectively. Here, we systematically investigated Nrf2 and NF-κB signaling upon DILI-related drug exposure. Transcriptomics analyses of 90 DILI compounds in primary human hepatocytes revealed that a strong Nrf2 activation is associated with a suppression of endogenous NF-κB activity. These responses were translated into quantitative high-content live-cell imaging of induction of a selective Nrf2 target, GFP-tagged Srxn1, and the altered nuclear translocation dynamics of a subunit of NF-κB, GFP-tagged p65, upon TNFR signaling induced by TNFα using HepG2 cells. Strong activation of GFP-Srxn1 expression by DILI compounds typically correlated with suppression of NF-κB nuclear translocation, yet reversely, activation of NF-κB by TNFα did not affect the Nrf2 response. DILI compounds that provided strong Nrf2 activation, including diclofenac, carbamazepine and ketoconazole, sensitized toward TNFα-mediated cytotoxicity. This was related to an adaptive primary protective response of Nrf2, since loss of Nrf2 enhanced this cytotoxic synergy with TNFα, while KEAP1 downregulation was cytoprotective. These data indicate that both Nrf2 and NF-κB signaling may be pivotal in the regulation of DILI. We propose that the NF-κB-inhibiting effects that coincide with a strong Nrf2 stress response likely sensitize liver cells to pro-apoptotic signaling cascades induced by intrinsic cytotoxic pro-inflammatory cytokines

An illness-focused interactive booklet to optimise management and medication for childhood fever and infections in out-of-hours primary care: study protocol for a cluster randomised trial

Background Fever is the most common reason for a child to be taken to a general practitioner (GP), especially during out-of-hours care. It is mostly caused by self-limiting infections. However, antibiotic prescription rates remain high, especially during out-of-hours care. Anxiety and lack of knowledge among parents, and perceived pressure to prescribe antibiotics amongst GPs, are important determinants of excessive antibiotic prescriptions. An illness-focused interactive booklet has the potential to improve this by providing parents with information about fever self-management strategies. The aim of this study is to develop and determine the effectiveness of an interactive booklet on management of children presenting with fever at Dutch GP out-of-hours cooperatives. Methods/design We are conducting a cluster randomised controlled trial (RCT) with 20 GP out-of-hours cooperatives randomised to 1 of 2 arms: GP access to the illness-focused interactive booklet or care as usual. GPs working at intervention sites will have access to the booklet, which was developed in a multistage process. It consists of a traffic light system for parents on how to respond to fever-related symptoms, as well as information on natural course of infections, benefits and harms of (antibiotic) medications, self-management strategies and ‘safety net’ instructions. Children < 12 years of age with parent-reported or physician-measured fever are eligible for inclusion. The primary outcome is antibiotic prescribing during the initial consultation. Secondary outcomes are (intention to) (re)consult, antibiotic prescriptions during re-consultations, referrals, parental satisfaction and reassurance. In 6 months, 20,000 children will be recruited to find a difference in antibiotic prescribing rates of 25% in the control group and 19% in the intervention group. Statistical analysis will be performed using descriptive statistics and by fitting two-level (GP out-of-hours cooperative and patient) random intercept logistic regression models. Discussion This will be the first and largest cluster RCT evaluating the effectiveness of an illness-focused interactive booklet during GP out-of-hours consultations with febrile children receiving antibiotic prescriptions. It is hypothesised that use of the booklet will result in a reduced number of antibiotic prescriptions, improved parental satisfaction and reduced intention to re-consult