Prioritizing research challenges and funding for allergy and asthma and the need for translational research—The European Strategic Forum on Allergic Diseases

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision‐makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real‐world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients’ organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.     

Identification of the cleavage site involved in production of plasma soluble Fc gamma receptor type III (CD16)

CD16 (Fcγ R type III) is a low-affinity IgG Fc receptor (R) that exists in two isoforms, a transmembrane FcγRIIIa expressed by NK cells and monocytes, and a phosphatidylinositol-linked FcγRIIIb expressed by neutrophils. A soluble form of CD16 (sCD16) circulates in plasma. The cleavage site and the nature of the enzyme(s) involved in production of sCD16 were investigated. Soluble CD16 was purified to apparent homogeneity from human serum by eight steps, including anion exchange and immunoaffinity chromatography. Serum sCD16 was sequenced at both ends, as well as a recombinant form of sCD16 used as control. N-terminal sequencing demonstrated that serum sCD16 originates from neutrophil FcγRIIIb and C-terminal sequencing suggested that the cleavage site is between Val 196 and Ser 197, close to the membrane anchor. Addition of a hydroxamate-based inhibitor of Zn²⁺ metalloproteinases (RU36156) led to a dramatic decrease of sCD16 production by phorbol 12-myristate 13-acetate-activated neutrophils, whereas inhibitors of serine proteinases had no significant effect, showing the metalloproteinase dependence of this cleavage process.     

Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization

Nimesulide, salicylic acid and their binary mixtures were studied by differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The study of such systems is a promising and viable approach for solving the problem of poor solubility of materials in general and drug systems in particular. All areas of human activity are inextricably linked to materials, and thus, the study presented in the paper and not reported in the literature is very important and provides useful data for those working in various fields. The eutectic mixtures were obtained by mechanosynthesis and by recrystallization from ethanol over the entire 0–1 range of molar fractions. For both situations at the molar fraction of nimesulide 0.5, the mixture has a eutectic that suggests an increase in solubility at this composition. The interactions that take place between the components were determined with the help of the excess thermodynamic functions (G^E, S^E, µ^E), which highlight the deviation from the ideality of the considered binary systems.     

Automatic bad channel detection in intracranial electroencephalographic recordings using ensemble machine learning

Objective

Intracranial electroencephalographic (iEEG) recordings contain “bad channels”, which show non-neuronal signals. Here, we developed a new method that automatically detects iEEG bad channels using machine learning of seven signal features.

Neurological complications of hematopoietic cell transplantation in children and adults

Hematopoietic cell transplantation(HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen(HLA)-matched donor(allogeneic) or from the patient(autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease(Gv HD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT:(1) early complications(in the first month)-related to harvesting of stem cells, during conditioning(drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia,(2) intermediate phase complications(second to sixth month)-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,(3) late phase complications(after sixth month)-neurological complications of Gv HD, second neoplasms and relapses of the original disease.     

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis

Background

22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms.

Methods

In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17–25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC.

Results

We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal–frontal, frontal–parietal, and frontal–occipital ROIs. In contrast, FC between ROIs in the parietal–temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus.

Conclusions

Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.

     

Low fermentable oligosaccharides,disaccharides, monosaccharides,and polyols diet in children

Irritable bowel syndrome (IBS) is a lifelong condition with a high prevalence among children and adults. As the diet is a frequent factor that triggers the symptoms, it has been assumed that by avoiding the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP), the symptoms might be improved. Therefore, in the past decade, low FODMAP diet has been intensively investigated in the management of IBS. The capacity of FODMAPs to trigger the symptoms in patients with IBS was related to the stimulation of mechanoreceptors in the small and large intestine. This stimulation appears as a response to a combination of increased luminal water (the osmotic effect) and the release of gases (carbon dioxide and hydrogen) due to the fermentation of oligosaccharides and malabsorption of fructose, lactose and polyols. Numerous studies have been published regarding the efficacy of a low FODMAP diet compared to a traditional diet in releasing the IBS symptoms in adults, but there are only a few studies in the juvenile population. The aim of this review is to analyze the current data on both low FODMAP diet in children with IBS and the effects on their nutritional status and physiological development, given the fact that it is a restrictive diet.     

The role of forensic medicine and forensic dentistry in estimating the chronological age of living individuals in Hamburg,Germany

International Journal of Legal Medicine - Age estimation represents one of the primary responsibilities of forensic medicine and forensic dentistry. It is an integral procedure aiming to estimate...     

Matrix‐Metalloproteinase‐2 Predicts Arteriovenous Fistula Failure in Hemodialysis Patients

In hemodialysis patients the principal cause of arteriovenous fistula dysfunction is stenosis. Matrix‐metalloproteinase‐2 is implicated in the pathophysiological mechanism of stenosis development. Our study tried to assess the clinical impact of this protease on arteriovenous fistula survival. Seventy‐nine prevalent dialysis patients with functional arteriovenous fistulas were included in the study. The presence of stenosis and the serum levels of matrix‐metalloproteinase‐2 were determined at the beginning of the study. The patency of the arteriovenous fistulas was followed‐ up for two years. In multivariate regression; matrix‐metalloproteinase‐2 was a significant predictor of vascular access loss (HR = 1.104, 95%CI 1.033–1.179, P = 0.003). Patients with a level of matrix‐metalloproteinase‐2 lower than 50 ng/mL had a better survival of the arteriovenous fistulas. Matrix‐metalloproteinase‐2 was an even stronger predictor of fistula failure in the stenosis group (HR = 1.076, 95%CI 1.027–1.127, P = 0.002). In our study matrix‐metalloproteinase‐2 has a predictive value for arteriovenous fistula failure.