Vibratory Urticaria Associated with a Missense Variant in ADGRE2.

Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE-independent vibration-induced degranulation. (Funded by the National Institutes of Health.).

Distress tolerance among emergency department patients in acute pain: Associations with substance use treatment.

Managing acute pain in individuals with a history of substance use disorders (SUD) is complex. Distress tolerance (DT) (e.g., the ability to handle uncomfortable sensations) may serve as an ideal non-pharmacological intervention target in this population. Among 293 emergency department (ED) patients seeking treatment for pain (Mage  = 41; 42% Female; 43% Black), we examined rates of SUD treatment and DT, whether an objective DT task is feasible to conduct in the ED, and relationships between DT and SUD. Patients completed a self-report DT survey, an objective DT task, and brief surveys of pain, drug use, current or past SUD treatment, and depression/anxiety. Average DT was 18.50 (SD = 9.4) out of 50; patients with past or current SUD treatment (n = 43; 14.7%) reported lower DT than patients with no SUD treatment history (n = 250; 85.3%). Controlling for demographics, depression/anxiety, and pain severity, lower subjective DT (adjusted odds ratio [aOR] = 1.05) and objective DT (aOR = 1.02) was associated a current or past history or SUD treatment. Assessing subjective and objective DT in ED patients with acute pain is feasible; interventions aimed at boosting DT may improve outcomes among patients with acute pain and SUD.

Skewed Lymphocyte Subpopulations and Associated Phenotypes in Patients with Mastocytosis.

BACKGROUND: Mastocytosis is a clonal mast cell disorder associated with elevated mast cell mediators, which themselves have been reported to affect lymphocyte function. However, the impact of an expanded mast cell compartment on lymphocyte subpopulations, and their correlation with clinical phenotypes in patients with indolent systemic mastocytosis (ISM), has not been explored. OBJECTIVE: To examine the immunophenotype of circulating lymphocytes in patients with ISM compared with healthy adult controls and examine relationships with aspects of clinical disease. METHODS: We examined lymphocyte subsets in 20 adult patients with ISM and 40 healthy adult volunteers by multiparameter flow cytometry. Results were correlated with clinical characteristics. RESULTS: Patients with ISM exhibited a significantly lower median frequency and absolute cell count of both circulating CD8+ T cells and natural killer cells accompanying a significantly increased ratio of CD4+/CD8+ T cells when compared with healthy volunteers. Stratification of our ISM patient cohort according to clinical manifestations revealed that CD19+CD21lowCD38low B cells were significantly higher in patients with a history of autoimmune disease and counts of terminally differentiated CD4+ T cells were significantly higher in patients with osteoporosis or osteopenia. CONCLUSIONS: Several circulating lymphocyte subpopulations in patients with ISM were significantly different when compared with healthy controls; in specific lymphocyte subsets, this lymphocyte skewing correlated with clinical observations including osteoporosis and autoimmune disease. These data suggest the need for further studies on abnormalities in lymphocyte subsets and the attendant clinical consequences in both mast cell proliferative and activation disorders.

Facing the new facts of retirement income adequacy.

A range of new factors is responsible for the current problem with insufficient retirement resources. Changes inside and outside the organization share partial responsibility, as do employee behaviors. In addition, other factors simply have been overlooked as employers and employees think about retirement income adequacy. The authors describe the current situation, discuss the significant risks it creates for both employers and employees and advise employers on what they should do to help employees build a more secure future in retirement.

Retirements at risk: employees lack a comprehensive, realistic view of resources and needs.

Employees who are following conventional retirement-planning advice will be in for a rude awakening as they approach retirement and discover that they can't afford to retire just yet or are likely to outlive their retirement funds. The article discusses how we have arrived at this point, what the implications are, and what both employers and employees can do to remedy the situation.