Cytokine expression patterns in hospitalized children with Bordetella pertussis, Rhinovirus or co-infection

Mechanisms of interaction between Bordetella pertussis and other viral agents are yet to be fully explored. We studied the inflammatory cytokine expression patterns among children with both viral-bacterial infections. Nasopharyngeal aspirate (NPA) samples were taken from children, aged < 1 year, positive for Rhinovirus, Bordetella pertussis and for Rhinovirus and Bordetella pertussis. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Our results show that co-infections display a different inflammatory pattern compared to single infections, suggesting that a chronic inflammation caused by one of the two pathogens could be the trigger for exacerbation in co-infections

Bond percolation on isoradial graphs: criticality and universality

In an investigation of percolation on isoradial graphs, we prove the criticality of canonical bond percolation on isoradial embeddings of planar graphs, thus extending celebrated earlier results for homogeneous and inhomogeneous square, triangular, and other lattices. This is achieved via the star-triangle transformation, by transporting the box-crossing property across the family of isoradial graphs. As a consequence, we obtain the universality of these models at the critical point, in the sense that the one-arm and 2j-alternating-arm critical exponents (and therefore also the connectivity and volume exponents) are constant across the family of such percolation processes. The isoradial graphs in question are those that satisfy certain weak conditions on their embedding and on their track system. This class of graphs includes, for example, isoradial embeddings of periodic graphs, and graphs derived from rhombic Penrose tilings.Comment: In v2: extended title, and small changes in the tex

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders

Leishmania infantum leishmaniasis in corticosteroid – treated patients

BACKGROUND: The number of leishmaniasis cases associated with immunosuppression has increased regularly over the past 20 years. Immunosuppression related to HIV infection, immunosuppressive treatment, organ transplantation, and neoplastic diseases increases the risk for Leishmania-infected people to develop visceral illness. CASE PRESENTATION: Three cases of Leishmania infantum leishmaniasis in corticosteroid (CS)-treated patients are reported: an isolated lingual leishmaniasis in a farmer treated with CS for asthma, a severe visceral leishmaniasis associated with cutaneous lesions in a woman with myasthenia gravis, and a visceral involvement after cutaneous leishmaniasis in a man receiving CS. CONCLUSION: Physicians should recognise CS-treated patients as a population likely to be immunesuppressed. In immunodeficiency conditions, unusual forms of leishmaniasis can develop and foster the risk of a diagnostic delay and of poor response to therapy

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

A Case of Infantile Alexander Disease Accompanied by Infantile Spasms Diagnosed by DNA Analysis

Alexander disease (AD) is a rare leukodystrophy of the central nervous system of unknown etiology. AD is characterized by progressive failure of central myelination and the accumulation of Rosenthal fibers in astrocytes, and is inevitably lethal in nature. Symptomatically, AD is associated with leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in infants, and usually leads to death within the first decade. Its characteristic magnetic resonance imaging (MRI) findings have been described as demyelination predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene, coding for glial fibrillary acidic protein (GFAP), a principal astrocytic intermediate filament protein, have been shown to lead to AD. The disease can now be detected by genetic diagnosis. We report the Korean case of an 8-month-old male patient with AD. He was clinically characterized due to the presence of psychomotor retardation, megalencephaly, spasticity, and recurrent seizures including infantile spasms which is a remarkable presentation. Demyelination in the frontal lobe and in a portion of the temporal lobe was demonstrated by brain MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L mutation in the GFAP gene, involving the replacement of guanine with thymine

1Design of the Primary Prevention Parameters Evaluation (PREPARE) trial of implantablecardioverter defibrillators to reduce patient morbidity [NCT00279279]

BACKGROUND: Implantable Cardioverter Defibrillator (ICD) therapy has been proven to be beneficial and efficacious for the treatment of serious ventricular tachyarrhythmias in primary prevention patients. However, primary prevention patients appear to have a lower incidence of ventricular arrhythmias in comparison to secondary prevention patients and consequently likely experience a higher proportion of detections due to supraventricular arrhythmias. Recent trials have demonstrated that strategic and specific programming choices reduce the number of inappropriate shocks and that anti-tachycardia pacing (ATP) is an effective alternative to shock therapy for many sustained ventricular arrhythmias. METHODS: The Primary Prevention Parameters Evaluation (PREPARE) study is a multi-center cohort study, evaluating the efficacy of a pre-specified strategic profile of VT/VF detection and therapy settings in 700 primary prevention patients in an effort to safely reduce the number of shock therapies delivered. The patients, both with and without cardiac resynchronization therapy, are compared to a well-qualified set (n = 691) of historical controls derived from the MIRACLE ICD and EMPIRIC trials. This manuscript describes the design of the PREPARE study. The study results, to be presented separately, will characterize the efficacy of this programming set (PREPARE) compared with physician-tailored programming (MIRACLE ICD and EMPIRIC)

Dose to level I and II axillary lymph nodes and lung by tangential field radiation in patients undergoing postmastectomy radiation with tissue expander reconstruction

<p>Abstract</p> <p>Background</p> <p>To define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT) following tissue expander placement.</p> <p>Methods and Materials</p> <p>Twenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose.</p> <p>Results</p> <p>The mean coverage of the level I/II axillary volume by the 95% isodose line (V_D95%) was 23.9% (range 0.3 - 65.4%). The mean Ipsilateral Lung V_D50%was 8.8% (2.2-20.9). Ipsilateral and contralateral expander volume correlated to Axillary V_D95%in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively) but not those with ipsilateral only reconstruction (p = 0.60). Ipsilateral Lung V_D50%correlated with angle of the expander from midline (p = 0.05).</p> <p>Conclusions</p> <p>In patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated.</p