Effective suckling in relation to naked maternal-infant body contact in the first hour of life: an observation study

Background Best practice guidelines to promote breastfeeding suggest that (i) mothers hold their babies in naked body contact immediately after birth, (ii) babies remain undisturbed for at least one hour and (iii) breastfeeding assistance be offered during this period. Few studies have closely observed the implementation of these guidelines in practice. We sought to evaluate these practices on suckling achievement within the first hour after birth. Methods Observations of seventy-eight mother-baby dyads recorded newborn feeding behaviours, the help received by mothers and birthing room practices each minute, for sixty minutes. Results Duration of naked body contact between mothers and their newborn babies varied widely from 1 to 60 minutes, as did commencement of suckling (range = 10 to 60 minutes). Naked maternal-infant body contact immediately after birth, uninterrupted for at least thirty minutes did not predict effective suckling within the first hour of birth. Newborns were four times more likely to sustain deep rhythmical suckling when their chin made contact with their mother’s breast as they approached the nipple (OR 3.8; CI 1.03 - 14) and if their mothers had given birth previously (OR 6.7; CI 1.35 - 33). Infants who had any naso-oropharyngeal suctioning administered at birth were six times less likely to suckle effectively (OR .176; CI .04 - .9). Conclusion Effective suckling within the first hour of life was associated with a collection of practices including infants positioned so their chin can instinctively nudge the underside of their mother’s breast as they approach to grasp the nipple and attach to suckle. The best type of assistance provided in the birthing room that enables newborns to sustain an effective latch was paying attention to newborn feeding behaviours and not administering naso-oropharyngeal suction routinely

Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation

Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. In this study, we utilized segmental allergen challenge (SAC) of allergic asthmatics (AA) and allergic non-asthmatic controls (AC) to determine if there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4+ T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin and increased MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC subjects, suggesting differences in the airway epithelial response to inflammation. Finally, AA subjects had increased airway smooth muscle mass at baseline measured in vivo using novel orientation-registered optical coherence tomography (OR-OCT). Our data demonstrate that the development of allergic asthma is dependent on the responsiveness of allergen-specific CD4+ T cells to innate type 2 mediators as well as increased sensitivity of airway epithelial cells and smooth muscle to type 2 inflammation

Self-citations at the meso and individual levels: effects of different calculation methods

This paper focuses on the study of self-citations at the meso and micro (individual) levels, on the basis of an analysis of the production (1994–2004) of individual researchers working at the Spanish CSIC in the areas of Biology and Biomedicine and Material Sciences. Two different types of self-citations are described: author self-citations (citations received from the author him/herself) and co-author self-citations (citations received from the researchers’ co-authors but without his/her participation). Self-citations do not play a decisive role in the high citation scores of documents either at the individual or at the meso level, which are mainly due to external citations. At micro-level, the percentage of self-citations does not change by professional rank or age, but differences in the relative weight of author and co-author self-citations have been found. The percentage of co-author self-citations tends to decrease with age and professional rank while the percentage of author self-citations shows the opposite trend. Suppressing author self-citations from citation counts to prevent overblown self-citation practices may result in a higher reduction of citation numbers of old scientists and, particularly, of those in the highest categories. Author and co-author self-citations provide valuable information on the scientific communication process, but external citations are the most relevant for evaluative purposes. As a final recommendation, studies considering self-citations at the individual level should make clear whether author or total self-citations are used as these can affect researchers differently

Aspergillus fumigatus Stimulates the NLRP3 Inflammasome through a Pathway Requiring ROS Production and the Syk Tyrosine Kinase

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K+ efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1β expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1β. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1β; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine

P. brasiliensis virulence is affected by SconC, the negative regulator of inorganic sulfur assimilation

Conidia/mycelium-to-yeast transition of Paracoccidioidesbrasiliensis is a critical step for the establishment of paracoccidioidomycosis, a systemic mycosis endemic in Latin America. Thus, knowledge of the factors that mediate this transition is of major importance for the design of intervention strategies. So far, the only known pre-requisites for the accomplishment of the morphological transition are the temperature shift to 37°C and the availability of organic sulfur compounds. In this study, we investigated the auxotrophic nature to organic sulfur of the yeast phase of Paracoccidioides, with special attention to P. brasiliensis species. For this, we addressed the role of SconCp, the negative regulator of the inorganic sulfur assimilation pathway, in the dimorphism and virulence of this pathogen. We show that down-regulation of SCONC allows initial steps of mycelium-to-yeast transition in the absence of organic sulfur compounds, contrarily to the wild-type fungus that cannot undergo mycelium-to-yeast transition under such conditions. However, SCONC down-regulated transformants were unable to sustain yeast growth using inorganic sulfur compounds only. Moreover, pulses with inorganic sulfur in SCONC down-regulated transformants triggered an increase of the inorganic sulfur metabolism, which culminated in a drastic reduction of the ATP and NADPH cellular levels and in higher oxidative stress. Importantly, the down-regulation of SCONC resulted in a decreased virulence of P. brasiliensis, as validated in an in vivo model of infection. Overall, our findings shed light on the inability of P. brasiliensis yeast to rely on inorganic sulfur compounds, correlating its metabolism with cellular energy and redox imbalances. Furthermore, the data herein presented reveal SconCp as a novel virulence determinant of P. brasiliensis.J.F.M. and J.G.R. were supported by a PhD grant from Fundacao para a Ciencia e Tecnologia (FCT). This work was supported by a grant from FCT (PTDC/BIA-MIC/108309/2008). M. Sturme. and M. Saraiva are Ciencia 2008 fellows. The authors would also like to thank FAPESP (Fundacao para Amparo a Pesquisa do Estado de Sao Paulo) and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Expansion of CD4+CD25+ and CD25- T-Bet, GATA-3, Foxp3 and RORγt Cells in Allergic Inflammation, Local Lung Distribution and Chemokine Gene Expression

Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2′-deoxyuridine (BrdU) together with 7-aminoactnomycin (7-AAD). The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet+, GATA-3+, RORγt+ and Foxp3+ cells in CD4+CD25+ and CD4+CD25- T cells, with the greatest expansion of GATA-3+ cells. The majority of CD4+CD25+ T-bet+, GATA-3+, RORγt+ and Foxp3+ cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet+, GATA-3+ and Foxp3+ cells in peribronchial and alveolar tissue, GATA-3+ and Foxp3+ cells in perivascular tissue, and RORγt+ cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu