Separation-survivability - the elusive moral cut-off point?

LetterThe original publication is available at http://www.samj.org.za[No abstract available]Publisher’s versio

Prognostic implications of mean nuclear diameter in breast cancer.

The mean nuclear diameter of 100 breast cancers was measured on tissue sections, to evaluate its importance for early prognosis. The cases were subdivided into 3 subgroups: small (25.5% of cases), medium (63.3%) and large (11.2%) nuclei. Early recurrence and mortality rates were investigated in each of the categories. Increasing nuclear size was shown to be related to mortality from metastatic disease. However, large-nucleus tumours had an inverse relationship with lymphnode involvement and possibly with recurrence rate. Hence, in our material nuclear size as a sole criterion was not a good indicator of the early behaviour of operable breast cancer

Attending school after treatment for a brain tumor: Experiences of children and key figures

Reintegration into school is a milestone for childhood brain tumor survivors, as well as for their parents, teachers, and healthcare providers. We explored their experiences following the school re-entry by conducting semi-structured interviews. Thematic analysis resulted in four main themes: "school performance," "psychosocial well-being," "support and approach," and "communication and collaboration." Children were pleased to return to school despite confrontation with adverse outcomes. Parents, teachers, and healthcare providers identified current and future concerns and challenges, as well as opportunities for academic and personal development. Their experiences highlight the importance of coordinated and systematic follow-up in close collaboration with healthcare providers

Nasopharyngeal microbiota in children is associated with severe asthma exacerbations

Background: The respiratory microbiome has been associated with the etiology and disease course of asthma. Objective: We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection. Methods: A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2 to 6 years (n = 87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n = 182). The nasopharyngeal microbiota was characterized by 16S-rRNA-gene sequencing. Results: Cases showed higher Shannon diversity index (ICU and MCU combined; P = .002) and a distinct microbial community composition when compared with controls (permutational multivariate ANOVA R2 = 1.9%; P &lt; .001). We observed significantly higher abundance of Staphylococcus and “oral” taxa, including Neisseria, Veillonella, and Streptococcus spp. and a lower abundance of Dolosigranulum pigrum, Corynebacterium, and Moraxella spp. (MaAsLin2; q &lt; 0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2, P = .03; q = 0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptococcus abundances were related with recent inhaled corticosteroid use. We observed no correlations with viral infection. Conclusions: Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and “oral” microbes and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and require further investigations.</p

Short-term perspectives of parents and teachers on school reintegration of childhood brain tumour survivors

OBJECTIVE: To discover short-term changes in perspectives of parents and teachers of childhood brain tumour survivors on school reintegration, in order to reveal similarities and differences between them over time. METHODS: Semi-structured interviews were conducted with parents and teachers of five children at the start and the end of a 1-year period following the child\u27s school re-entry. RESULTS: Thematic analysis of data resulted in three main themes: \u27the child\u27s performance and wellbeing\u27, \u27the school\u27s attitude and approach\u27 and \u27communication and working together\u27. Parental concerns about child-specific changes and the school\u27s approach to the child could either decrease or increase over time. Teachers remained focused on assessing their pupil\u27s learning potential and finding ways of appropriate support. Their different perspectives on communication and working together became more pronounced. CONCLUSIONS: This study emphasizes the importance of clear communication and collaboration, coordinated follow-up and availability of healthcare professionals during the child\u27s school reintegration

Effect of Seven-Valent Pneumococcal Conjugate Vaccine on Staphylococcus aureus Colonisation in a Randomised Controlled Trial

Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents. Methodology/Principal Findings: This study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1: 1: 1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n = 336), 2+1-doses (336) or no dose (n = 333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p = 0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38-0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52-0.88). Conclusions/Significance: PCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted

The MrCYP52 Cytochrome P450 Monoxygenase Gene of Metarhizium robertsii Is Important for Utilizing Insect Epicuticular Hydrocarbons

Fungal pathogens of plants and insects infect their hosts by direct penetration of the cuticle. Plant and insect cuticles are covered by a hydrocarbon-rich waxy outer layer that represents the first barrier against infection. However, the fungal genes that underlie insect waxy layer degradation have received little attention. Here we characterize the single cytochrome P450 monoxygenase family 52 (MrCYP52) gene of the insect pathogen Metarhizium robertsii, and demonstrate that it encodes an enzyme required for efficient utilization of host hydrocarbons. Expressing a green florescent protein gene under control of the MrCYP52 promoter confirmed that MrCYP52 is up regulated on insect cuticle as well as by artificial media containing decane (C10), extracted cuticle hydrocarbons, and to a lesser extent long chain alkanes. Disrupting MrCYP52 resulted in reduced growth on epicuticular hydrocarbons and delayed developmental processes on insect cuticle, including germination and production of appressoria (infection structures). Extraction of alkanes from cuticle prevented induction of MrCYP52 and reduced growth. Insect bioassays against caterpillars (Galleria mellonella) confirmed that disruption of MrCYP52 significantly reduces virulence. However, MrCYP52 was dispensable for normal germination and appressorial formation in vitro when the fungus was supplied with nitrogenous nutrients. We conclude therefore that MrCYP52 mediates degradation of epicuticular hydrocarbons and these are an important nutrient source, but not a source of chemical signals that trigger infection processes

Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines