Oral Immunotherapy for Peanut Allergy in Children 1 to Less Than 4 Years of Age.

BACKGROUND: Peanut allergy is a common childhood allergy, and the only approved treatment for children 4 to 17 years of age is peanut allergen powder-dnfp (PTAH) oral immunotherapy. METHODS: For this phase 3, randomized, double-blind, placebo-controlled trial, we enrolled peanut-allergic children 1 to <4 years of age who experienced dose-limiting symptoms from ≤300 mg peanut protein during a screening double-blind, placebo-controlled food challenge (DBPCFC). Participants received PTAH or placebo, randomized in a 2:1 ratio, for approximately 12 months.

A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development.

Craniofacial abnormalities account for approximately one third of birth defects. The regulatory programs that build the face require precisely controlled spatiotemporal gene expression, achieved through tissue-specific enhancers. Clusters of coactivated enhancers and their target genes, known as superenhancers, are important in determining cell identity but have been largely unexplored in development.

Long-term safety and immunologic outcomes of daily oral immunotherapy for peanut allergy.

Background: Oral immunotherapy containing peanut () allergen powder-dnfp (PTAH) (Palforzia [Aimmune Therapeutics, Brisbane, Calif]) for 9 to 12 months resulted in higher tolerated amounts of peanut protein in PTAH-treated individuals aged 4 to 17 years with peanut allergy than in placebo-treated participants.

Objective: We aimed to describe additional long-term pooled safety data and changes in peanut sensitization markers from baseline through approximately 5 years of treatment.

Methods: The results from 6 clinical trials of PTAH (3 controlled and 3 open-label extension studies [N = 1227]) were pooled, and analysis of safety outcomes and immunologic data was performed.

Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation.

Primary cilia are nearly ubiquitous organelles that transduce molecular and mechanical signals. Although the basic structure of the cilium and the cadre of genes that contribute to ciliary formation and function (the ciliome) are believed to be evolutionarily conserved, the presentation of ciliopathies with narrow, tissue-specific phenotypes and distinct molecular readouts suggests that an unappreciated heterogeneity exists within this organelle. Here, we provide a searchable transcriptomic resource for a curated primary ciliome, detailing various subgroups of differentially expressed genes within the ciliome that display tissue and temporal specificity.

Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism.

The mechanistic details of the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered. We set out to investigate the physiological importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116 in vitro and in vivo.

Participant characteristics and safety outcomes of peanut oral immunotherapy in the RAMSES and ARC011 trials.

Background: Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment.

Objective: To describe PTAH safety and tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFCs during trials and to compare findings with previously published data.

Project ECHO in the Caribbean: Building a Virtual Community for Palliative Care Education Needs.

Despite a growing need, palliative care education tools tailored to providers in the Caribbean remain extremely limited. We conducted a mixed methods analysis of the first Project ECHO (Extension for Community Healthcare Outcomes) model adapted for palliative care providers in the Caribbean. These virtual, case-based sessions were held to enhance regional palliative care providers' knowledge of symptom management, communication, and psychosocial support.

Analysis of the glyco-code in pancreatic ductal adenocarcinoma identifies glycan-mediated immune regulatory circuits.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a 5-year survival rate of only 9%. Despite the fact that changes in glycosylation patterns during tumour progression have been reported, no systematic approach has been conducted to evaluate its potential for patient stratification. By analysing publicly available transcriptomic data of patient samples and cell lines, we identified here two specific glycan profiles in PDAC that correlated with progression, clinical outcome and epithelial to mesenchymal transition (EMT) status.

Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with peanut allergy: Pooled summary of phase 3 and extension trials.

Background: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years.

Objective: We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment.

Methods: Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed.

Centriolar Protein C2cd3 Is Required for Craniofacial Development.

The primary cilium is a ubiquitous, microtubule-based cellular organelle. Primary cilia dysfunction results in a group of disorders termed ciliopathies. C2 domain containing 3 centriole elongation regulator (C2cd3), encodes a centriolar protein essential for ciliogenesis.

Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency.

Background: Adenylosuccinate lyase deficiency (ADSLD) is an ultrarare neurometabolic recessive disorder caused by loss-of-function mutations in the ADSL gene. The disease is characterized by wide clinical variability. Here we provide an updated clinical profiling of the disorder and discuss genotype-phenotype correlations.

Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9.

Changes in glycosylation during tumour progression are a key hallmark of cancer. One of the glycan moieties generally overexpressed in cancer are sialic acids, which can induce immunomodulatory properties via binding to Siglec receptors. We here show that Pancreatic Ductal Adenocarcinoma (PDAC) tumour cells present an increased sialylation that can be recognized by Siglec-7 and Siglec-9 on myeloid cells.

Head-to-head comparison of DFO* and DFO chelators: selection of the best candidate for clinical Zr-immuno-PET.

Purpose: Almost all radiolabellings of antibodies with Zr currently employ the hexadentate chelator desferrioxamine (DFO). However, DFO can lead to unwanted uptake of Zr in bones due to instability of the resulting metal complex. DFO*-NCS and the squaramide ester of DFO, DFOSq, are novel analogues that gave more stable Zr complexes than DFO in pilot experiments.

Glucocorticoid regulates mesenchymal cell differentiation required for perinatal lung morphogenesis and function.

While antenatal glucocorticoids are widely used to enhance lung function in preterm infants, cellular and molecular mechanisms by which glucocorticoid receptor (GR) signaling influences lung maturation remain poorly understood. Deletion of the glucocorticoid receptor gene () from fetal pulmonary mesenchymal cells phenocopied defects caused by global deletion, while lung epithelial- or endothelial-specific deletion did not impair lung function at birth. We integrated genome-wide gene expression profiling, ATAC-seq, and single cell RNA-seq data in mice in which GR was deleted or activated to identify the cellular and molecular mechanisms by which glucocorticoids control prenatal lung maturation.

Cancer invasion into musculature: Mechanics, molecules and implications.

Tumor invasion along structural interphases of surrounding tumor-free tissue represents a key process during tumor progression. Much attention has been devoted to mechanisms of tumor cell migration within extracellular matrix (ECM)-rich connective tissue, however a comprehensive understanding of tumor invasion into tissue of higher structural complexity, such as muscle tissue, is lacking. Muscle invasion in cancer patients is often associated with destructive growth and worsened prognosis.

Alveolar injury and regeneration following deletion of ABCA3.

Adaptation to air breathing after birth is dependent upon the synthesis and secretion of pulmonary surfactant by alveolar type 2 (AT2) cells. Surfactant, a complex mixture of phospholipids and proteins, is secreted into the alveolus, where it reduces collapsing forces at the air-liquid interface to maintain lung volumes during the ventilatory cycle. ABCA3, an ATP-dependent Walker domain containing transport protein, is required for surfactant synthesis and lung function at birth.

Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling.

Pulmonary function is dependent upon the precise regulation of alveolar surfactant. Alterations in pulmonary surfactant concentrations or function impair ventilation and cause tissue injury. Identification of the molecular pathways that sense and regulate endogenous alveolar surfactant concentrations, coupled with the ability to pharmacologically modulate them both positively and negatively, would be a major therapeutic advance for patients with acute and chronic lung diseases caused by disruption of surfactant homeostasis.

Maternal dietary intake in pregnancy and lactation and allergic disease outcomes in offspring.

As the prevalence of allergic disease dramatically rises worldwide, prevention strategies are increasingly being considered. Given the potential modulatory effect of nutritional factors on disease, altering maternal diet during pregnancy and/or lactation has been considered in preventing allergic disease in offspring. Although there are a number of observational studies that have examined possible associations between maternal diet and allergic outcomes in offspring, interventional trials are limited.

Clinically relevant outcome measures of novel pharmacotherapy for nonallergic rhinitis.

Purpose Of Review: The purpose of this review is to briefly provide the current understanding of the pathogenesis of nonallergic rhinitis (NAR), currently available pharmacotherapies as well as some recent advancement in pharmacotherapy for this condition. With this background on NAR, we then describe and contrast outcome measures used in previous NAR and allergic rhinitis clinical trials. Finally, we conclude with a brief discussion on which of these outcomes might be most suitable for future NAR clinical trials.

Shoulder pain and dysfunction secondary to neural injury.

Study Design: Resident's Case Study

Background/introduction: The reports of spinal accessory nerve injury in the literature primarily focus on injury following surgical dissection or traumatic stretch injury. There is limited literature describing the presentation and diagnosis of this injury with an unknown cause. The purpose of this case report is to describe the clinical decision-making process that guided the diagnosis and treatment of a complex patient with spinal accessory nerve palsy (SANP) whose clinical presentation and response to therapy were inconsistent with the results of multiple diagnostic tests.

Airway peroxidases catalyze nitration of the {beta}2-agonist salbutamol and decrease its pharmacological activity.

β(2)-agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β(2)-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hydrogen peroxide (H(2)O(2)) and nitrite (NO(2)(-)), both absorption spectroscopy and mass spectrometry indicated formation of a new metabolite with features expected for the nitrated drug.

Electrochemical synthesis and characterization of transparent nanocrystalline Cu2O films and their conversion to CuO films.

Transparent nanocrystalline Cu2O films (Eg = 2.6 eV) were electrodeposited from a dimethyl sulfoxide medium; these films exhibit interesting optical and photoelectrochemical properties, and can be converted to transparent CuO films.