Abstract Background Although the provision of pediatric emergency and trauma radiology has become increasingly prevalent in North America over the last few years, many hospitals differ in their models of providing after-hours coverage. Objective To describe the scope of after-hours radiology services provided in children’s hospitals in North America, and...
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Sulforaphane (SFN), a potent antioxidant and anti-inflammatory agent, has been shown to protect against cancers especially at early stages. However, how SFN affects UVB-mediated epigenome/DNA methylome and transcriptome changes in skin photodamage has not been fully assessed. Herein, we investigated the transcriptomic and DNA methylomic changes during tumor initiation, promotion, and progression and its impact and reversal by SFN using next-generation sequencing (NGS) technology. The results show...
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S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function, and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation...
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Cas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a’s natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays...
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The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces the dextran of the highest molar mass reported to date (~109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very high molar mass polymer. In the domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of Glycoside-Hydrolase 70 (GH70)...
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Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system (CNS) diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers...
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The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2–mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 [PNPLA8]), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids....
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Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signalling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP downregulation in AML primary cells...
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Abstract An abnormal collection of air in the thorax is one of the most common life-threatening events that occurs in the intensive care unit. Patient management differs depending on the location of the air collection; therefore, detecting abnormal air collection and identifying its exact location on supine chest radiographs is essential for early treatment and positive patient outcomes. Thoracic abnormal air collects in multiple thoracic spaces, including the pleural cavity,...
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BackgroundThis research aimed to analyse the psychophysiological modifications of a rescuer helicopter crew in a crane rescue manoeuvre.MethodsWe analysed in eight participants (32.5±6.6 years) divided in four categories (pilot, mechanic, rescuer and control) with variables of anxiety, rating of perceived exertion (RPE), stress subjective perception (SSP), heart rate, blood oxygen saturation (BOS), skin temperature, blood lactate, cortical arousal, autonomic modulation, legs and hands strength, legs...
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Checkpoint kinase 1 (CHK1) is a key mediator of the DNA damage response that regulates cell cycle progression, DNA damage repair and DNA replication. Small-molecule CHK1 inhibitors sensitise cancer cells to genotoxic agents and have shown single agent preclinical activity in cancers with high levels of replication stress. However, the underlying genetic determinants of CHK1 inhibitor sensitivity remain unclear. We used the developmental clinical drug SRA737 in an unbiased large-scale siRNA screen...
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Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models,...
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Evidence of Possible Irritable Larynx Syndrome in Obstructive Sleep Apnea: An Epidemiologic Approach
“Irritable larynx syndrome” (ILS) often refers to a constellation of laryngeal-based symptoms including chronic cough (CC), diurnal dyspnea, and dysphonia. In patients with OSA, we examined: (1) the frequency, severity, comorbidity, risks and triggers of each problem, (2) whether these symptoms were compatible with stereotypic ILS and (3) the role of CPAP in their expression.
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Abstract Anticonvulsant drugs have a high risk of adverse drug events. Little is known about the perception of those events by pediatric patients. We performed a survey in the neuropediatric departments of two university hospitals. Using a questionnaire, we interviewed patients aged 6–18 years with current anticonvulsant treatment regarding (i) their fears about potential adverse drug events, (ii) experienced adverse drug events, and (iii) perceived burden of experienced adverse...
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Abstract Primary immunodeficiency disorders represent a heterogeneous spectrum of diseases, predisposing to recurrent infections, allergy, and autoimmunity. While an association between primary immunodeficiency disorders and increased risk of cancer has been suggested since the 1970s, renewed attention has been given to this topic in the last decade, largely in light of the availability of large registries as well as advances in next generation sequencing. In this narrative review,...
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The gene encoding alpha-1 antitrypsin (SERPINA1) is the strongest genetic risk locus for Chronic obstructive pulmonary disease (COPD) susceptibility. While the deficiency alleles PI types S and Z increase the risk for COPD in ZZ homozygotes and ZS compound heterozygotes as compared with wild-type allele homozygotes (MM), contradictory data exists regarding MZ heterozygotes. Ortega et al (Am J Respir Crit Care Med. 2019 Oct 29. https://doi.org/10.1164/rccm.201904-0769OC) performed deep next-generation...
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Smell dysfunction has a significant impact on quality of life (QOL), potentially leading to food poisoning, a reduction in appetite and eventually malnutrition, immunity reduction, and worsening of medical illness.1
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The following activities offer AMA PRA Category 1 Credit™ and meet the American Board of Allergy and Immunology (ABAI) requirements for Part II or Part IV Maintenance of Certification (MOC):
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With the increasing recognition of the role of type 2 immune responses in chronic rhinosinusitis, its severity, recurrence, and comorbidities, several biologics targeting IL-4, IL-5, and IL-13 as well as IgE have been administered in small proof-of-concept studies. Recently, the first phase 3 trials have been reported with dupilumab, an IL-4 receptor antagonist, demonstrating a significant and clinically relevant reduction of the disease burden from polyp size and sinus involvement to symptoms and...
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With regard to the article in the December 2019 issue entitled “Exacerbation-prone asthma in the context of race and ancestry in Asthma Clinical Research Network Trials” (J Allergy Clin Immunol 2019;144:1524-33), the authors would like to make a correction: “In the Methods Section we stated that, ‘Genome-wide genotyping data from the TALC/BASALT cohorts (290 NHW, 110 Blacks, and 75 other) and the SLIC/SOCS/IMPACT cohorts from the NHLBI Database of Genotypes and Phenotypes (dbGaP) SNP Health Association...
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Thank you to every eligible voting member who participated in the 2020 Board of Directors election. Your votes have helped shape the future of the AAAAI and the specialty.
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Increasing prevalence of asthma and allergic disease has been linked to changes in diet including lower consumption of n-3 long-chain polyunsaturated fatty acids (PUFAs) and higher consumption of n-6 PUFAs. In this issue, Rosa et al (p 800) extended our understanding of these relationships by investigating the association of maternal n-3 and n-6 PUFA status and the ratio of the 2 in relation to the risk of asthma in children at ages 4-6 years, as well as how maternal asthma and child sex modified...
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Chronic rhinosinusitis (CRS) is one of the most common chronic diseases worldwide. It is a heterogeneous disease, and geographical or ethnic differences in inflammatory pattern in nasal mucosa are major issues. Tissue eosinophilia in CRS is highly associated with extensive sinus disease, recalcitrance, and a higher nasal polyp (NP) recurrence rate after surgery. The prevalence of eosinophilic CRS (ECRS) is increasing in Asian countries within the last 2 decades, and this trend appears to be occurring...
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects 1% to 4% of the Western population and is associated with major impact on quality of life. Its pathogenesis, combining hair follicle dysregulation and both skin and systemic inflammation, involves a genetic background interacting with environmental factors (eg, bacterial skin dysbiosis, overweight, smoking).1 TNF-α, which is enhanced in HS, is upregulated in other immune-mediated inflammatory diseases (IMIDs) such as...
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Abstract Titanium dioxide nanoparticles (TiO2NPs) have been widely used as food additives in daily life. However, the impact of oral intake of TiO2NPs on the nervous system is largely unknown. In this study, 7-week-old mice were treated with either vehicle or TiO2NPs suspension solution at 150 mg/kg by intragastric administration for 30 days. Our results demonstrated that oral exposure to TiO2NPs resulted in aberrant excitement of enteric neurons, although unapparent pathological...
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Abstract Amorphous silica nanoparticles are widely used as pharmaceutical excipients and food additive (E551). Despite the potential human health risks of mineral nanoparticles, very few data regarding their oral toxicity are currently available. This study aims to evaluate and to understand the interactions of silica particles at 1 and 10 mg mL−1 with the intestinal barrier using a Caco-2 monolayer and a Caco-2/HT29-MTX co-culture. A size- and concentration-dependent reversible...
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Abstract Background This systematic review aimed to review the literature on interventions for improving self‐management and wellbeing in adolescents and young adults (11‐25 years) with asthma and allergic conditions. Methods A systematic literature search was undertaken across eight databases. References were checked by two reviewers for inclusion. Study data were extracted and their quality was assessed in duplicate. A narrative synthesis was undertaken. Results A total...
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Abstract Biosynthesized nanoparticles proposed to have antiplasmodial activities have attracted increasing attention for malaria that considered being one of the foremost hazardous diseases. In this study, Indigofera oblongifolia leaf extracts were used for the synthesis of silver nanoparticles (AgNPs), which were characterized utilizing transmission electron microscopy. We investigated the antiplasmodial and hepatoprotective effects of AgNPs against Plasmodium chabaudi–induced...
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