While the diagnosis and initial treatment of eosinophilic esophagitis are becoming more standardized, there are still major gaps in knowledge related to measuring treatment response. One such ...question centers on how to measure treatment response and what treatment endpoints should be. This impacts not only patient care and engagement in decision-making, but also the field of drug development. In addition, studies so far have use a myriad of treatment endpoints including over a dozen histologic endpoint criteria. This review will discuss the various stakeholders involved in assessment of treatment endpoints of a complex condition, including patients, practitioners and regulatory agencies, and the care settings in which treatment response is assessed, including routine clinical care, clinical trials, and observational studies. Potential parameters or treatment endpoints such as histology, symptoms, patient-reported outcomes, endoscopy, and biomarkers are discussed along with associated challenges and opportunities. A framework on how to define treatment outcomes is discussed and a conceptual approach treatment response is proposed. This takes into account histology, symptoms, and endoscopic findings and harnesses existing, validated tools. It includes definitions of nonresponse, complete normalization, and a graded response category between these 2 extremes, and also permits flexibility and latitude for modifications as newer knowledge emerges. In addition, ways to position the pediatric population in these endeavors are discussed as are future research directions.
Herein we report air-stable Dy(iii) and Er(iii) single-ion magnets (SIMs) with pseudo-
symmetry, synthesized from a sterically encumbered phosphonamide,
BuPO(NH
Pr)
, where the Dy(iii)-SIM exhibits a ...magnetization blocking (
) up to 12 K, defined from the maxima of the zero-field cooled magnetization curve, with an anisotropy barrier (
) as high as 735.4 K. The Dy(iii)-SIM exhibits a magnetic hysteresis up to 12 K (30 K) with a large coercivity of ∼0.9 T (∼1.5 T) at a sweep rate of ∼0.0018 T s
(0.02 T s
). These high values combined with persistent stability under ambient conditions, render this system as one of the best-characterized SIMs.
calculations have been used to establish the connection between the higher-order symmetry of the molecule and the quenching of quantum tunnelling of magnetization (QTM) effects. The relaxation of magnetization is observed
the second excited Kramers doublet owing to pseudo-high-order symmetry, which quenches the QTM. This study highlights fine-tuning of symmetry around the lanthanide ion to obtain new-generation SIMs and offers further scope for pushing the limits of
and
using this approach.
Pathophysiology of Eosinophilic Esophagitis O’Shea, Kelly M.; Aceves, Seema S.; Dellon, Evan S. ...
Gastroenterology (New York, N.Y. 1943),
01/2018, Volume:
154, Issue:
2
Journal Article
Peer reviewed
Open access
Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life ...environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming growth factor beta production and signaling, to eosinophilic esophagitis pathophysiology. Experimental modeling has defined a cooperative role of activated eosinophils, mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization to multiple foods. Understanding these processes is opening the way to better treatment based on disrupting allergic inflammatory and type 2 cytokine–mediated responses, including anti-cytokine therapeutics and dietary therapy.
Methane is one of the critical greenhouse gases, which absorb long wavelength radiation, affects the chemistry of atmosphere and contributes to global climate change. Rice ecosystem is one of the ...major anthropogenic sources of methane. The anaerobic waterlogged soil in rice field provides an ideal environment to methanogens for methanogenesis. However, the rate of methanogenesis differs according to rice cultivation regions due to a number of biological, environmental and physical factors like carbon sources, pH, Eh, temperature etc. The interplay between the different conditions and factors may also convert the rice fields into sink from source temporarily. Mechanistic understanding and comprehensive evaluation of these variations and responsible factors are urgently required for designing new mitigation options and evaluation of reported option in different climatic conditions. The objective of this review paper is to develop conclusive understanding on the methane production, oxidation, and emission and methane measurement techniques from rice field along with its mitigation/abatement mechanism to explore the possible reduction techniques from rice ecosystem.
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•Water management (controlled irrigation and midseason drying) is the best CH4 mitigating option in irrigated rice field.•Ammonium based fertilizer having up to 60% CH4 mitigation potential.•Biofertilizer (Azolla and Cynobacteria) are best for sustainable rice cultivation.•Microbial fuel cells are the least explore mitigation option in flooded rice field.
Using a pyrazolate‐bridged dinucleating ligand that provides two proximate pincer‐type PNN binding sites (“two‐in‐one pincer”), different synthetic routes have been developed towards its dicobalt(I) ...complex 2 that features a twice deprotonated ligand backbone and two weakly activated terminal N2 substrate ligands directed into the bimetallic pocket. Protonation of 2 is shown to occur at the ligand scaffold and to trigger conversion to a tetracobalt(I) complex 4 with two end‐on μ1,2‐bridging N2; in THF 4 is labile and undergoes temperature‐dependent N2/triflate ligand exchange. These pyrazolate‐based systems combine the potential of exhibiting both metal–metal and metal–ligand cooperativity, viz. two concepts that have emerged as promising design motifs for molecular N2 fixation catalysts. Complex 2 serves as an efficient (pre)catalyst for the reductive silylation of N2 into N(SiMe3)3 (using KC8 and Me3SiCl), yielding up to 240 equiv N(SiMe3)3 per catalyst.
A ligand scaffold with two fused PNN pincer compartments combines two beneficial features for N2 fixation with molecular catalysts, viz. a bimetallic pocket and ligand‐based protonation sites. Its cobalt(I) dinitrogen complexes are shown to efficiently mediate the reductive silylation of N2.
The infection with SARS-CoV-2 is reported to be accompanied by the shedding of the virus in fecal samples of infected patients. Earlier reports have suggested that COVID-19 agents can be present in ...the sewage samples and thus it can be a good indication of the pandemic extent in a community. However, no such studies have been reported in the Indian context. Hence, it becomes absolutely necessary to detect the presence of the SARS-CoV-2 in the wastewater samples from wastewater treatment plants (WWTPs) serving different localities of Jaipur city. Samples from different WWTPs and hospital wastewater samples were collected and wastewater based epidemiology (WBE) studies were carried out using the RT-PCR to confirm the presence of different COVID-19 target genes namely S gene, E gene, ORF1ab gene, RdRp gene and N gene. The results revealed that the untreated wastewater samples showed the presence of SARS-CoV-2 viral genome, which was correlated with the increased number of COVID-19 positive patients from the concerned areas, as reported in the publically available health data. This is the first study that investigated the presence of SARS-CoV-2 viral genome in wastewater, at higher ambient temperature (45 °C), further validating WBE as potential tool in predicting and mitigating outbreaks.
Bronchopneumonia is a common respiratory disease in livestock. Mannheimia haemolytica is considered the main causative pathogen leading to lung damage in sheep, with Mycoplasma ovipneumoniae and ...ParaInfluenza virus type 3, combined with adverse physical and physiological stress, being predisposing factors. A balance of humoral and cellular immunity is thought to be important for protection against developing respiratory disease. In the current study, we compared the ability of the trehalose glycolipid adjuvant C18Brar (C18-alkylated brartemicin analogue) and three commercially available adjuvant systems i.e., Quil-A, Emulsigen-D, and a combination of Quil-A and aluminium hydroxide gel, to stimulate antibody and cellular immune responses to antigens from inactivated whole cells of M. haemolytica and M. ovipneumoniae in sheep. C18Brar and Emulsigen-D induced the strongest antigen-specific antibody responses to both M. haemolytica and M. ovipneumoniae, while C18Brar and Quil-A promoted the strongest antigen-specific IL-17A responses. The expression of genes with known immune functions was determined in antigen-stimulated blood cultures using Nanostring nCounter technology. The expression levels of CD40, IL22, TGFB1, and IL2RA were upregulated in antigen-stimulated blood cultures from animals vaccinated with C18Brar, which is consistent with T-cell activation. Collectively, the results demonstrate that C18Brar can promote both antibody and cellular responses, notably Th17 immune responses in a ruminant species.
The global food demand is expected to increase in the coming years, along with challenges around climate change and food security. Concomitantly, food safety risks, particularly those related to ...bacterial pathogens, may also increase. Thus, the food sector needs to innovate to rise to this challenge. Here, we discuss recent advancements in molecular techniques that can be deployed within various foodborne bacteria surveillance systems across food settings. To start with, we provide updates on nucleic acid‐based detection, with a focus on polymerase chain reaction (PCR)‐based technologies and loop‐mediated isothermal amplification (LAMP). These include descriptions of novel genetic markers for several foodborne bacteria and progresses in multiplex PCR and droplet digital PCR. The next section provides an overview of the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐associated (Cas) proteins systems, such as CRISPR‐Cas9, CRISPR‐Cas12a, and CRISPR‐Cas13a, as tools for enhanced sensitive and specific detection of foodborne pathogens. The final section describes utilizations of whole genome sequencing for accurate characterization of foodborne bacteria, ranging from epidemiological surveillance to model‐based predictions of bacterial phenotypic traits through genome‐wide association studies or machine learning.
Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ...'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.
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