Effect of excess weight and insulin resistance on DNA methylation in prepubertal children.

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children.

Pulmonary Procedures During the COVID-19 Pandemic: A Work Group Report of the AAAAI Asthma Diagnosis and Treatment (ADT) Interest Section.

The COVID-19 pandemic has placed increased demands on the ability to safely perform pulmonary procedures in keeping with Centers for Disease Control and Prevention (CDC), American Thoracic Society (ATS), and the Occupational Safety and Health Administration (OSHA) recommendations. Accordingly, the American Academy of Allergy, Asthma & Immunology (AAAAI) Asthma Diagnosis and Treatment convened this work group to offer guidance. The work group is composed of specialist practitioners from academic and both large and small practices.

Anti-PD-1/L1 lead-in before MAPK inhibitor combination maximizes antitumor immunity and efficacy.

Rationally sequencing and combining PD-1/L1-and MAPK-targeted therapies may overcome innate and acquired resistance. Since increased clinical benefit of MAPK inhibitors (MAPKi) is associated with previous immune checkpoint therapy, we compare the efficacies of sequential and/or combinatorial regimens in subcutaneous murine models of melanoma driven by Braf, Nras, or Nf1 mutations as well as colorectal and pancreatic carcinoma driven by Kras. Anti-PD-1/L1 lead-in preceding MAPKi combination optimizes response durability by promoting pro-inflammatory polarization of macrophages and clonal expansion of interferon-γ, and CD8 cytotoxic and proliferative (versus CD4 regulatory) T cells that highly express activation genes.

The challenge of asthma in adolescent athletes: exercise induced bronchoconstriction (EIB) with and without known asthma.

Exercise induced bronchconstriction (EIB) is defined as a transient increase in airway resistance reflected as at least a 10% decline in FEV1 following at least 6-8 minutes of strenuous exercise. Up to 90% of asthmatics, 45% of individuals with allergic rhinitis, 50% of Olympic athletes, and 12% of the general population have EIB. EIB in adolescence may be either under- or over-diagnosed because of denial of symptoms or misperception of dyspnea or other respiratory symptoms.

An update on exercise-induced bronchoconstriction with and without asthma.

Exercise-induced bronchoconstriction (EIB) is defined as transient, reversible bronchoconstriction that develops after strenuous exercise. It is a heterogeneous syndrome made up of a spectrum of phenotypes ranging from the asymptomatic military recruit whose condition is detected by diagnostic exercise challenge to the athlete with known asthma to the elite athlete for whom EIB represents an overuse or injury syndrome. If exercise is the only identified trigger for bronchoconstriction, it is called EIB.

Changes in NGF and NT-3 protein species in the superior cervical ganglion following axotomy of postganglionic axons.

Mature sympathetic neurons in the superior cervical ganglion (SCG) are regulated by target-derived neurotrophins such as nerve growth factor (NGF) and neurotrophin-3 (NT-3). High molecular weight NGF species and mature NT-3 are the predominant NGF and NT-3 protein isoforms in the SCG, yet it is unknown whether the presence of these species is dependent on intact connection with the target tissues. In an attempt to determine the role of peripheral targets in regulating the neurotrophin species found in the SCG, we investigated the NGF and NT-3 protein species present in the SCG following axotomy (transection) or injury of the post-ganglionic axons.

Exercise-induced bronchospasm in children.

This review will encompass definition, history, epidemiology, pathogenesis, diagnosis, and management of exercise -induced bronchospasm in the pediatric individual with and without known asthma. Exercise induced asthma is the conventional term for transient airway narrowing in a known asthma in association with strenuous exercise usually lasting 5-10 minutes with a decline in pulmonary function by at least 10%. Exercise induced asthma will be referred to as exercise induced bronchospasm in an asthmatic.

Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input.

Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are target-derived proteins that regulate innervating sympathetic neurons. Here, we used western blot analysis to investigate changes in NGF and NT-3 protein in several peripheral tissues following loss of sympathetic input. Following removal of the superior cervical ganglion (SCG), large molecular weight (MW) NGF species, including proNGF-A, were increased in distal intracranial SCG targets, such as pineal gland and extracerebral blood vessels (bv).

Making the diagnosis of asthma in the athlete.

This article encompasses a discussion of the clinical presentation and features as various diagnostic modalites of bronchoprovocation and differential diagnosis used in screening for asthma in the athlete. A comparative analysis of these modalities, including questionnaire, treadmill, eucapneic hyperventilation, as well as field challenge, is provided with sensitivities and specificities, predictive value, and application to clinical practice. The indication and mechanics of each diagnostic modality is discussed, providing the clinician with a comprehensive understanding of the principles and procedures used to diagnosis asthma in the athlete.

The syndrome of thyroid autoimmunity and idiopathic chronic urticaria and angioedema presenting as anaphylaxis.

Previous observations have shown that the syndrome of thyroid autoimmunity and idiopathic urticaria and angioedema (ICUA) can be associated with a marked worsening of reactive airway disease. Possibly, mediators released in this syndrome may contribute to acute bronchospasm and associated respiratory symptoms in some patients. In this study, two patients presenting with overlapping clinical presentations of the syndrome of thyroid immunity and ICUA are described in whom a diagnosis of anaphylaxis to food and antibiotics, respectively, was initially suspected but ruled out by testing and challenges.