Inflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis.
The serum levels of 13 cytokines and their relation to ...clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil-lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls.
CRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls - including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) - yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu.
CRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed.
Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support ...clinical decision-making to optimize treatment for children with this condition.This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines.Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient's journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working.Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.
Higher-grade inflammatory infiltrate is a promising marker for better prognosis in colorectal cancer (CRC). However, the knowledge on the interrelationships between different inflammatory cells and ...classifications is fragmentary.
We analysed the densities of eight types of inflammatory cells in a prospectively recruited group of 117 CRC patients and determined their interrelationships and contributions to Klintrup-Mäkinen (K-M) score of overall peritumoural inflammation. We characterised the inflammatory infiltrate in relation to stage and recurrences in 24-month follow-up.
There were high positive correlations between the inflammatory cell densities, with the exception of mast cells and CD1a+ immature dendritic cells. High K-M score associated with high peri- and intratumoural densities of CD3+, CD8+, CD68+, CD83+, and FoxP3+ cells and neutrophils. Advanced stage associated with low K-M score, as well as low CD3+, CD8+, CD83+, and FoxP3+ cell counts, of which low K-M score, low CD3(+) T-cell count, and low FoxP3+ T-cell count were linked to higher recurrence rate.
The density of CRC inflammatory infiltrate declines as stage advances. Especially, low K-M score and low T-cell counts predict higher recurrence rate. The high positive correlations between the individual inflammatory markers support the value of overall inflammatory reaction scoring.
Background
Component‐resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double‐blind placebo‐controlled challenges are lacking. We aimed to optimize ...diagnostics for moderate‐to‐severe peanut allergy in a birch‐endemic region and to create an oral‐peanut challenge with its allergen activity characterized.
Methods
We performed double‐blind placebo‐controlled peanut challenges for a referred sample of 6‐ to 18‐year‐olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (sIgE) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition.
Results
Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI, 0.96–1.00) was the best marker of moderate‐to‐severe allergy. When sIgE to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value, AUC 0.42 (95%CI, 0.30–0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity.
Conclusion
Co‐sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component‐resolved diagnostics reduce the need for oral challenges in peanut allergy.
Aromatic compounds derived from lignin are of great interest for renewable biotechnical applications. They can serve in many industries e.g. as biochemical building blocks for bioplastics or ...biofuels, or as antioxidants, flavor agents or food preservatives. In nature, lignin is degraded by microorganisms, which results in the release of homocyclic aromatic compounds. Homocyclic aromatic compounds can also be linked to polysaccharides, tannins and even found freely in plant biomass. As these compounds are often toxic to microbes already at low concentrations, they need to be degraded or converted to less toxic forms. Prior to ring cleavage, the plant- and lignin-derived aromatic compounds are converted to seven central ring-fission intermediates, i.e. catechol, protocatechuic acid, hydroxyquinol, hydroquinone, gentisic acid, gallic acid and pyrogallol through complex aromatic metabolic pathways and used as energy source in the tricarboxylic acid cycle. Over the decades, bacterial aromatic metabolism has been described in great detail. However, the studies on fungal aromatic pathways are scattered over different pathways and species, complicating a comprehensive view of fungal aromatic metabolism. In this review, we depicted the similarities and differences of the reported aromatic metabolic pathways in fungi and bacteria. Although both microorganisms share the main conversion routes, many alternative pathways are observed in fungi. Understanding the microbial aromatic metabolic pathways could lead to metabolic engineering for strain improvement and promote valorization of lignin and related aromatic compounds.
Summary
The Finnish and Russian Karelia are adjacent areas in northern Europe, socio‐economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize ...the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non‐existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti‐inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10‐year National Allergy Programme was started in 2008 to combat the epidemic in Finland.
This paper introduces a new method for generating nanoscale coatings in a continuous roll-to-roll process at normal pressure. Nanostructured and transparent coating, based on titanium dioxide ...nanoparticles, was successfully deposited on-line at atmospheric conditions on pigment coated paperboard using a thermal spray method called the Liquid Flame Spray (LFS). The LFS coating process is described and the influences of process parameters on coating quality are discussed. Nanocoating was investigated by a field emission gun scanning electron microscope (FEG-SEM), an atomic force microscope (AFM), an X-ray photoelectron spectroscopy (XPS) and a water contact angle measurement.
The highest measured water contact angles on the nanocoated paperboard surface were over 160°. Falling water droplets were able to bounce off the surface, which is illustrated by high speed video system images. Regardless of the high hydrophobicity, the coating showed sticky nature, creating a high adhesion to water droplets immediately as the motion of the droplets stopped. Nanocoating with full coverage of the substrate was produced at line speeds up to 150
m/min. Therefore, the LFS coating has scale up potential to industrial level as an affordable and efficient method for coating large volumes at high line speeds.
B7-H3, an immunoregulatory protein, is overexpressed in several cancers and is often associated with metastasis and poor prognosis. Here, our aim was to identify microRNAs (miRNAs) regulating B7-H3 ...and assess their potential prognostic implications in breast cancer.
MicroRNAs targeting B7-H3 were identified by transfecting two breast cancer cell lines with a library of 810 miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate microarrays. For validations we used western immunoblotting and 3'-UTR luciferase assays. Clinical significance of the miRNAs was assayed by analysing whether their expression levels correlated with outcome in two cohorts of breast cancer patients (142 and 81 patients).
We identified nearly 50 miRNAs that downregulated B7-H3 protein levels. Western immunoblotting validated the impact of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and miR-593) targeted B7-H3 directly by binding to its 3'-UTR region. Finally, high expression of miR-29c was associated with a significant reduced risk of dying from breast cancer in both cohorts.
We identified miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c correlated with survival in breast cancer patients, suggesting a tumour suppressive role for this miRNA.
Summary
Background
Atopic allergy has been more common among schoolchildren in Finland, as compared to Russian Karelia. These adjacent regions show one of the most contrasting socio‐economical ...differences in the world.
Objective
We explored changes in allergy from school age to young adulthood from 2003 to 2010/2012 in these two areas. The skin and nasal microbiota were also compared.
Methods
Randomly selected children from Finnish (n = 98) and Russian Karelia (n = 82) were examined in 2003, when the children were 7–11 years of age, and again in 2010 (Finnish Karelia) and 2012 (Russian Karelia). We analysed self‐reported allergy symptoms and sensitization to common allergens by serum sIgE values. The skin (volar forearm) and nasal mucosa microbiota, collected in 2012 (aged 15–20 years), identified from DNA samples, were compared with multivariate methods.
Results
Asthma, hay fever, atopic eczema, self‐reported rhinitis, as well as atopic sensitization, were threefold to 10‐fold more common in Finland, as compared to Russian Karelia. Hay fever and peanut sensitization were almost non‐existent in Russia. These patterns remained throughout the 10‐year follow‐up. Skin microbiota, as well as bacterial and fungal communities in nasal mucosa, was contrastingly different between the populations, best characterized by the diversity and abundance of genus Acinetobacter; more abundant and diverse in Russia. Overall, diversity was significantly higher among Russian subjects (Pskin < 0.0001, Pnasal‐bacteria < 0.0001 and Pnasal‐fungi < 0.01). Allergic diseases were not associated with microbial diversity in Finnish subjects.
Conclusions and Clinical Relevance
Differences in allergic phenotype, developed in early life, remain between populations. A parallel difference in the composition of skin and nasal microbiota suggests a potential underlying mechanism. Our results also suggest that high abundance and diversity of Acinetobacter might contribute to the low allergy prevalence in Russia. Implications of early‐life exposure to Acinetobacter should be further investigated.
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