Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium : a BelSACI-Abeforcal-EUFOREA statement

Allergic rhinitis (AR) affects 23-30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient-and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium

PolySilicate Porous Organic Polymers (PSiPOPs), a new family of porous, ordered 3D reticular materials with polysilicate nodes and organic linkers

Spherosilicate, consisting of a double 4-ring cyclosilicate core (D4R; Si8O20) with every corner functionalized with a dimethylsilyl chloride group (-SiMe2Cl), was used as node to construct an iso-reticular series of porous expanded network materials. Interconnecting the nodes with linear, aliphatic {\alpha},{\omega}-alkanediol linker molecules yields PolySilicate Porous Organic Polymers (PSiPOPs), a new type of ordered reticular material related to the well-known metal-organic and covalent organic frameworks (MOFs & COFs). In the synthesis, sacrificial hydrogen-bonded Si8O20 cyclosilicate crystals are first converted into silyl chloride terminated spherosilicate. In a second step, these nodes are linked up by alkanediol units via the intermediate formation of a Si-N bond with catalytic amines such as pyridine and dimethylformamide. Overall, the presented synthesis converts D4R cyclosilicate into an ordered reticular framework with [Si8O20]-[Si(CH3)2-]8 nodes and O-(CH2)n-O linkers. Example materials with ethylene glycol, 1,5-pentanediol, and 1,7-heptanediol as linker (n = 2, 5, and 7) were produced and characterized. On a macroscopic level, the synthesis yields porous frameworks exhibiting a thermal stability up to 400{\deg}C and a chemical stability between pH 1 and 12. N2 physisorption revealed a secondary mesopore structure, indicating future options to produce hierarchical materials using soft templates. The molecular level structure of these reticular PSiPOP materials was elucidated using an NMR crystallography approach implementing a combination of 1D and 2D 1H and 29Si solid-state MAS NMR spectroscopy experiments. Previously reported reticular COF/POP materials implementing D4R-based nodes, used Si8 octakis (phenyl) D4R POSS as a node, connecting it to the linker via a Si-C bond instead of a Si-O-C linkage

Can the combination of in situ differential impedance spectroscopy and 27Al NMR detect incongruent zeolite crystallization?

Crystallizing zeolites with isotropic properties is critical to the chemical industry but can be extremely challenging as small deviations in the synthesis conditions can have extreme effects on the final products. Easily implemented in-situ monitoring systems could make a real difference, but very few experimental methodologies cater to the specific needs of applications relying on harsh, hyper-alkaline conditions involving multiphasic systems such as Hydrated Silicate Ionic Liquids. Differential impedance spectroscopy (DIS) promises to enable such studies. It remains highly accurate despite possible electrode degradation or scaling. This study showcases how in-situ differential impedance measurements not only enable reliable detection of crystallization of even minimal amounts of zeolite product but also illustrates how the unique combination of in situ DIS and in situ, 27Al NMR provides insight into complex, incongruent zeolite crystallization processes

Non-contact in situ multi-diagnostic NMR/dielectric spectroscopy

Introduction of a dielectric material in an NMR probe head modifies the frequency response of the probe circuit, a phenomenon revealed by the detuning of the probe. For NMR spectroscopy, this detuning is corrected for by tuning and matching the probe head prior to the NMR measurement. The magnitude of the probe detuning - the dielectric shift - provides direct access to the dielectric properties of the sample, enabling NMR spectrometers to simultaneously perform both dielectric and NMR spectroscopy. By measuring sample permittivity as function of frequency, permittivity spectroscopy can be performed using the new methodology. As a proof concept, this was evaluated on methanol, ethanol, 1-propanol, 1-pentanol and 1-octanol using a commercial CPMAS NMR probe head. The results accurately match literature data collected by standard dielectric spectroscopy techniques. Subsequently, the method was also applied to investigate the solvent-surface interactions of water confined in the micropores of an MFI-type, hydrophilic zeolite with Si/Al ratio of 11.5. In the micropores, water adsorbs to Br{\o}nsted acid sites and defect sites, resulting in a drastically decreased dielectric permittivity of the nano-confined water. A theoretical background for the new methodology is provided using an effective electric circuit model of a CPMAS probe head with solenoid coil, describing the detuning resulting from insertion of dielectric samples in the probe head

SI methane hydrate confined in C8-grafted SBA-15: A highly efficient storage system enabling ultrafast methane loading and unloading

Confinement of water and methane in mesopores of hydrophobized SBA-15 is demonstrated to promote methane hydrate formation. In comparison to as-synthesized SBA-15, hydrophobization by C8 grafting accelerates the kinetics of methane storage in and delivery from the hydrate. C8 grafting density was determined at 0.5 groups nm-2 based on TGA and quantitative NMR spectroscopy. Multinuclear 1H-1H DQSQ and 1H-1H RFDR NMR provided spectroscopic evidence for the occurrence of C8 chains inside the mesopores of SBA-15, by showcasing close spatial proximity between the grafted C8 chains and pore-intruded water species. X-ray diffraction demonstrates formation of Structure I hydrate on SBA-15 C8. At 7.0 MPa and 248 K, the water-to-hydrate conversion on hydrophobized SBA-15 C8 reaches 96 pct. as compared to only 71 pct. on a pristine SBA-15 sample with comparable pore size, pore volume and surface area. The clathrate loading amounted to 14.8 g g-1. 2D correlation NMR spectroscopy (1H-13C CP-HETCOR, 1H-1H RFDR) reveals hydrate formation occurs within pores of SBA-15 C8 as well as in interparticle volumes. Following the initial crystallization of SBA-15 C8-supported methane hydrate taking several hours, a pressure swing process at 248 K allows to desorb and re-adsorb methane from the structure within minutes and without thawing the frozen water structure. Fast loading and unloading of methane was achieved in 19 subsequent cycles without losses in kinetics. The ability to harvest the gas and regenerate the structure without the need to re-freeze the water represents a 50 pct. energy gain with respect to melting and subsequently recrystallizing the hydrate at 298 K and 248 K, respectively. After methane desorption, a small amount of residual methane hydrate in combination with an amorphous yet locally ordered ice phase is observed using 13C and 2H NMR spectroscopy

Strongly Reducing (Diarylamino)benzene-Based Covalent Organic Framework for Metal-Free Visible Light Photocatalytic H2O2 Generation

Photocatalytic reduction of molecular oxygen is a promising route toward sustainable production of hydrogen peroxide (H2O2). This challenging process requires photoactive semiconductors enabling solar energy driven generation and separation of electrons and holes with high charge transfer kinetics. Covalent organic frameworks (COFs) are an emerging class of photoactive semiconductors, tunable at a molecular level for high charge carrier generation and transfer. Herein, we report two newly designed two-dimensional COFs based on a (diarylamino)benzene linker that form a Kagome (kgm) lattice and show strong visible light absorption. Their high crystallinity and large surface areas (up to 1165 m(2)center dot g(-1)) allow efficient charge transfer and diffusion. The diarylamine (donor) unit promotes strong reduction properties, enabling these COFs to efficiently reduce oxygen to form H2O2. Overall, the use of a metal-free, recyclable photocatalytic system allows efficient photocatalytic solar transformations.DFG, 390540038, EXC 2008: Unifying Systems in Catalysis "UniSysCat"EC/H2020/665501/EU/[PEGASUS]², giving wings to your career./PEGASUS-2EC/H2020/834134/EU/Water Forced in Hydrophobic Nano-Confinement: Tunable Solvent System/WATUSOEC/H2020/647755/EU/First principle molecular dynamics simulations for complex chemical transformations in nanoporous materials/DYNPO

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

7th Drug hypersensitivity meeting: part two

No abstract availabl

Intercellular interaction between FAP+ fibroblasts and CD150+inflammatory monocytes mediates fibrostenosis in Crohn's disease

Crohn’s disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.Cellular mechanisms in basic and clinical gastroenterology and hepatolog