The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children.

OBJECTIVE: Glutamine has been shown to promote heat shock protein 70 (HSP70) release both within experimental in vitro models of sepsis (2-10 mM) and in adults post trauma (0.5 g/kg), although the efficacy varies and is dependent on the model used. The effect of glutamine supplementation on HSP70 release in children is less clear. Therefore, the aim of this study was to investigate the effect of 2 mM glutamine added to incubation media on HSP70 and inflammatory mediator release in an in vitro model of paediatric sepsis using whole blood from healthy paediatric volunteers. METHODS: An in vitro whole blood endotoxin stimulation model using 1 μg/ml lipopolysaccharide (LPS) over a 24 h time period was used to investigate the effects of 2 mM glutamine on HSP70 and inflammatory mediator release in healthy children. RESULTS: The addition of 2 mM glutamine to the incubation media significantly increased HSP70 release over time (p < 0.05). This was associated with an early pro-inflammatory effect on TNF-α release at 4 h (p < 0.005) which was not seen at 24 h. There was a non significant trend towards higher levels of IL-6 and IL-10 following the addition of 2 mM glutamine, which appears to differ from the response reported in adult and animal models. CONCLUSION: Glutamine supplementation of incubation media promotes HSP70 and early TNF- α release in an in vitro model using blood samples from healthy children.This is the author accepted manuscript. The final version is available via Elsevier at http://dx.doi.org/10.1016/j.clnu.2014.12.00

Genome-wide association studies in infectious diseases.

One of the most puzzling questions facingboth parents and pediatricians is whysome children suffer severe and life-threatening infections, while others who are exposedto the same pathogen remain uninfected orsuffer only mild illness. There is now growingevidence that differences in host genetics playa major role in determining susceptibility andoutcome of childhood infections,1 in additionto environmental factors such as pathogenvirulence and exposure dos

Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection

Two rapid assays for screening of patulin biodegradation

Artículo sobre distintos ensayos para comprobar la biodegradación de la patulinaThe mycotoxin patulin is produced by the blue mould pathogen Penicillium expansum in rotting apples during postharvest storage. Patulin is toxic to a wide range of organisms, including humans, animals, fungi and bacteria. Wash water from apple packing and processing houses often harbours patulin and fungal spores, which can contaminate the environment. Ubiquitous epiphytic yeasts, such as Rhodosporidium kratochvilovae strain LS11 which is a biocontrol agent of P. expansum in apples, have the capacity to resist the toxicity of patulin and to biodegrade it. Two non-toxic products are formed. One is desoxypatulinic acid. The aim of the work was to develop rapid, high-throughput bioassays for monitoring patulin degradation in multiple samples. Escherichia coli was highly sensitive to patulin, but insensitive to desoxypatulinic acid. This was utilized to develop a detection test for patulin, replacing time-consuming thin layer chromatography or high-performance liquid chromatography. Two assays for patulin degradation were developed, one in liquid medium and the other in semi-solid medium. Both assays allow the contemporary screening of a large number of samples. The liquid medium assay utilizes 96-well microtiter plates and was optimized for using a minimum of patulin. The semisolid medium assay has the added advantage of slowing down the biodegradation, which allows the study and isolation of transient degradation products. The two assays are complementary and have several areas of utilization, from screening a bank of microorganisms for biodegradation ability to the study of biodegradation pathways

Plant responses to fertilization experiments in lowland, species-rich, tropical forests.

We present a meta-analysis of plant responses to fertilization experiments conducted in lowland, species-rich, tropical forests. We also update a key result and present the first species-level analyses of tree growth rates for a 15-yr factorial nitrogen (N), phosphorus (P), and potassium (K) experiment conducted in central Panama. The update concerns community-level tree growth rates, which responded significantly to the addition of N and K together after 10 yr of fertilization but not after 15 yr. Our experimental soils are infertile for the region, and species whose regional distributions are strongly associated with low soil P availability dominate the local tree flora. Under these circumstances, we expect muted responses to fertilization, and we predicted species associated with low-P soils would respond most slowly. The data did not support this prediction, species-level tree growth responses to P addition were unrelated to species-level soil P associations. The meta-analysis demonstrated that nutrient limitation is widespread in lowland tropical forests and evaluated two directional hypotheses concerning plant responses to N addition and to P addition. The meta-analysis supported the hypothesis that tree (or biomass) growth rate responses to fertilization are weaker in old growth forests and stronger in secondary forests, where rapid biomass accumulation provides a nutrient sink. The meta-analysis found no support for the long-standing hypothesis that plant responses are stronger for P addition and weaker for N addition. We do not advocate discarding the latter hypothesis. There are only 14 fertilization experiments from lowland, species-rich, tropical forests, 13 of the 14 experiments added nutrients for five or fewer years, and responses vary widely among experiments. Potential fertilization responses should be muted when the species present are well adapted to nutrient-poor soils, as is the case in our experiment, and when pest pressure increases with fertilization, as it does in our experiment. The statistical power and especially the duration of fertilization experiments conducted in old growth, tropical forests might be insufficient to detect the slow, modest growth responses that are to be expected

Effectiveness of interventions to promote healthy diet in primary care: systematic review and meta-analysis of randomised controlled trials

Background A diet rich in fruit, vegetables and dietary fibre and low in fat is associated with reduced risk of chronic disease. This review aimed to estimate the effectiveness of interventions to promote healthy diet for primary prevention among participants attending primary care.&lt;p&gt;&lt;/p&gt; Methods A systematic review of trials using individual or cluster randomisation of interventions delivered in primary care to promote dietary change over 12 months in healthy participants free from chronic disease or defined high risk states. Outcomes were change in fruit and vegetable intake, consumption of total fat and fibre and changes in serum cholesterol concentration.&lt;p&gt;&lt;/p&gt; Results Ten studies were included with 12,414 participants. The design and delivery of interventions were diverse with respect to grounding in behavioural theory and intervention intensity. A meta-analysis of three studies showed an increase in fruit consumption of 0.25 (0.01 to 0.49) servings per day, with an increase in vegetable consumption of 0.25 (0.06 to 0.44) serving per day. A further three studies that reported on fruit and vegetable consumption together showed a pooled increment of 0.50 (0.13 to 0.87) servings per day. The pooled effect on consumption of dietary fibre, from four studies, was estimated to be 1.97 (0.43 to 3.52) gm fibre per day. Data from five studies showed a mean decrease in total fat intake of 5.2% of total energy (1.5 to 8.8%). Data from three studies showed a mean decrease in serum cholesterol of 0.10 (-0.19 to 0.00) mmol/L.&lt;p&gt;&lt;/p&gt; Conclusion Presently-reported interventions to promote healthy diet for primary prevention in primary care, which illustrate a diverse range of intervention methods, may yield small beneficial changes in consumption of fruit, vegetables, fibre and fat over 12 months. The present results do not exclude the possibility that more effective intervention strategies might be developed.&lt;p&gt;&lt;/p&gt

Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D

<p>Abstract</p> <p>Background</p> <p>Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. Our previous work demonstrated that SP-D increases the uptake of SPP by alveolar macrophages. In the present study, we investigated the uptake of SPP in human primary epithelial cells and the potential modulation by SP-D. The patho-physiological consequence was evaluated by measurement of pro-inflammatory mediators.</p> <p>Methods</p> <p>SPP were isolated from timothy grass and subsequently fluorescently labelled. Human primary bronchial epithelial cells were incubated with SPP or polystyrene particles (PP) in the presence and absence of surfactant protein D. In addition, different sizes and surface charges of the PP were studied. Particle uptake was evaluated by flow cytometry and confocal microscopy. Soluble mediators were measured by enzyme linked immunosorbent assay or bead array.</p> <p>Results</p> <p>SPP were taken up by primary epithelial cells in a dose dependent manner. This uptake was coincided with secretion of Interleukin (IL)-8. SP-D increased the fraction of bronchial epithelial cells that bound SPP but not the fraction of cells that internalized SPP. SPP-induced secretion of IL-8 was further increased by SP-D. PP were bound and internalized by epithelial cells but this was not modulated by SP-D.</p> <p>Conclusions</p> <p>Epithelial cells bind and internalize SPP and PP which leads to increased IL-8 secretion. SP-D promotes attachment of SPP to epithelial cells and may thus be involved in the inflammatory response to inhaled allergen.</p

Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations: a case-control and observational cohort study

Summary Background Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department. Methods Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities. Findings A three-gene transcript signature, comprising HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0·976 (95% CI 0·919−1·000), sensitivity of 97·3% (85·8−99·9), and specificity of 100% (63·1−100). The AUROC for C-reactive protein (CRP) was 0·833 (0·694−0·944) and for leukocyte count was 0·938 (0·840−0·986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte count for discriminating viral infections from all other infections. In the second validation analysis, which included SARS-CoV-2-positive participants, the signature discriminated 35 bacterial infections from 34 SARS-CoV-2-positive COVID-19 infections with AUROC of 0·953 (0·893−0·992), sensitivity 88·6%, and specificity of 94·1%. Interpretation This novel three-gene signature discriminates viral infections, including COVID-19, from other emergency infection presentations in adults, outperforming both leukocyte count and CRP, thus potentially providing substantial clinical utility in managing acute presentations with infection. Funding National Institute for Health Research, Medical Research Council, Wellcome Trust, and EU-FP7

Cerebral palsy and placental infection: a case-cohort study

BACKGROUND: The association between cerebral palsy in very preterm infants and clinical, histopathologic and microbiological indicators of chorioamnionitis, including the identification of specific micro-organisms in the placenta, was evaluated in a case-cohort study. METHODS: Children with a diagnosis of cerebral palsy at five years of age were identified from amongst participants in a long-term follow-up program of preterm infants. The comparison group was a subcohort of infants randomly selected from all infants enrolled in the program. The placentas were examined histopathologically for chorioamnionitis and funisitis, and the chorioamnionic interface was aseptically swabbed and comprehensively cultured for aerobic and anaerobic bacteria, yeast and genital mycoplasmas. Associations between obstetric and demographic variables, indicators of chorioamnionitis and cerebral palsy status were examined by univariate analysis. RESULTS: Eighty-two infants with cerebral palsy were compared with the subcohort of 207 infants. Threatened preterm labor was nearly twice as common among the cases as in the subcohort (p < 0.01). Recorded clinical choroamnionitis was similar in the two groups and there was no difference in histopathologic evidence of infection between the two groups. E. coli was cultured from the placenta in 6/30 (20%) of cases as compared with 4/85 (5%) of subcohort (p = 0.01). Group B Streptococcus was more frequent among the cases, but the difference was not statistically significant. CONCLUSIONS: The association between E. coli in the chorioamnion and cerebral palsy in preterm infants identified in this study requires confirmation in larger multicenter studies which include microbiological study of placentas

Clinico-pathological profile of sinonasal masses: an experience in national ear care center Kaduna, Nigeria

<p>Abstract</p> <p>Background</p> <p>The presence of a mass in the nose and paranasal sinuses may seem to be a simple problem; however it raises many questions about the differential diagnosis. The aim of this study is to evaluate the clinico-pathological profile of sinonasal masses in our environment</p> <p>This is a retrospective analytical review of all the patients with sinonasal masses that presented to the national ear care center, Kaduna over a six year (2003-2008) period. Their biodata, clinical profile and histological diagnoses were analyzed.</p> <p>Findings</p> <p>A total of 76 patients were analyzed, age range 5 to 64 yrs with a mean age of 33.3 yr median and modal age of 35.00 (SD = 13.1 ± 1.5). Majority of the patients were in the age groups 21-50 yrs. There were 34 male and 42 female with M: F ratio of 1:1.2. The main presenting symptoms are nasal blockage 97.4% and rhinorrhea 94.7%. It was bilateral in 34 (44.7%), left side in 24(31.6%) and right side in 18(23.7%) patients. The commonest clinical diagnoses were simple nasal polyp 47(61.8%) and antrochoanal polyp 10(13.2%). About 59 (77.6%) were benign, 2 (2.6%) were malignant and 15 (19.7%) were lost to follow up. The commonest histological diagnosis is simple inflammatory nasal polyp in 28 (36.8%) patients and the least was nasal capillary hemangioma 2 (2.6%). About 55(72.4%) patients had surgical treatment.</p> <p>Conclusions</p> <p>Nasal obstruction and rhinorrhea are the commonest symptoms of presentation, simple inflammatory nasal polyp is still the commonest histological pattern seen in our environment, and surgery is still the best modality of treatment for benign tumor thus the need for advocacy for early recognition and referral to the ENT surgeon.</p