Bone marrow plasma cells require P2RX4 to sense extracellular ATP.

Plasma cells produce large quantities of antibodies and so play essential roles in immune protection1. Plasma cells, including a long-lived subset, reside in the bone marrow where they depend on poorly defined microenvironment-linked survival signals1. We show that bone marrow plasma cells use the ligand-gated purinergic ion channel P2RX4 to sense extracellular ATP released by bone marrow osteoblasts through the gap-junction protein pannexin 3 (PANX3). Mutation of Panx3 or P2rx4 each caused decreased serum antibodies and selective loss of bone marrow plasma cells. Compared to their wild-type counterparts, PANX3-null osteoblasts secreted less extracellular ATP and failed to support plasma cells in vitro. The P2RX4-specific inhibitor 5-BDBD abrogated the impact of extracellular ATP on bone marrow plasma cells in vitro, depleted bone marrow plasma cells in vivo and reduced pre-induced antigen-specific serum antibody titre with little posttreatment rebound. P2RX4 blockade also reduced autoantibody titre and kidney disease in two mouse models of humoral autoimmunity. P2RX4 promotes plasma cell survival by regulating endoplasmic reticulum homeostasis, as short-term P2RX4 blockade caused accumulation of endoplasmic reticulum stress-associated regulatory proteins including ATF4 and B-lineage mutation of the pro-apoptotic ATF4 target Chop prevented bone marrow plasma cell demise on P2RX4 inhibition. Thus, generating mature protective and pathogenic plasma cells requires P2RX4 signalling controlled by PANX3-regulated extracellular ATP release from bone marrow niche cells.

Psychosocial Outcomes of Age Integration Status: Do Age-Integrated Social Networks Benefit Older Adults?

Increased longevity means that older adults have more opportunities to have age-integrated social networks, which include both same-aged peers and intergenerational social ties. Compared to those with peer-only, or intergenerational-only social networks, those with age-integrated networks may experience greater psychosocial benefits due to the age-diverse nature of their social networks. Data from the National Health and Aging Trends Study was used to examine age integration status associations with well-being and social engagement in a nationally representative sample of Medicare beneficiaries in the United States. We hypothesized that age-integrated older adults have greater well-being and social engagement than older adults with peer-only or intergenerational-only networks. Weighted ordinary least squares regression analyses were conducted to test associations of well-being and social engagement with age integration status, controlling for sociodemographic and health covariates. Older adults with age-integrated social networks did not differ in well-being from those with peer-only or intergenerational-only networks, although they had greater social engagement than those with intergenerational-only networks.

Resting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation.

Little is known about how cells regulate and integrate distinct biosynthetic pathways governing differentiation and cell division. For B lineage cells it is widely accepted that activated cells must complete several rounds of mitosis before yielding antibody-secreting plasma cells. However, we report that marginal zone (MZ) B cells, innate-like naive B cells known to generate plasma cells rapidly in response to blood-borne bacteria, generate functional plasma cells despite cell-cycle arrest. Further, short-term Notch2 blockade in vivo reversed division-independent differentiation potential and decreased transcript abundance for numerous mTORC1- and Myc-regulated genes. Myc loss compromised plasma cell differentiation for MZ B cells, and reciprocally induced ectopic mTORC1 signaling in follicular B cells enabled division-independent differentiation and plasma cell-affiliated gene expression. We conclude that ongoing in situ Notch2/mTORC1 signaling in MZ B cells establishes a unique cellular state that enables rapid division-independent plasma cell differentiation.

Congenital Langerhans cell histiocytosis presenting in a 27-week-gestation neonate.

Langerhans cell histiocytosis is exceedingly rare in premature infants, and the few cases reported suggest a poor prognosis with systemic involvement. We present a case of Langerhans cell histiocytosis limited to a single cutaneous lesion, presenting in a 27-week-gestation infant, which is the youngest gestational age of reported Langerhans cell histiocytosis cases. The lesion showed spontaneous resolution by 41 weeks corrected gestational age, and systemic involvement was absent, demonstrating a mild course of skin-only Langerhans cell histiocytosis in a premature infant.

Discrimination and Depressive Symptoms Among African American Men Across the Adult Lifecourse.

Objectives: A lifecourse framework was used to examine the association between major and everyday measures of perceived discrimination and depressive symptoms among African American men and to evaluate whether these relationships differed for young, middle-aged, and older men. Method: The association between both major and everyday discrimination and depressive symptoms, as measured by the Center for Epidemiologic Studies Depression (CES-D) scale, was assessed among 296 African American men in the 2011-2014 Nashville Stress and Health Study (NSAHS) using ordinary least squares regression. Interactive associations between major and everyday discrimination and age patterns in the discrimination-depressive symptoms relationship were also investigated. Results: Everyday, but not major discrimination was associated with depressive symptoms among African American men. This relationship was stronger among middle-aged men and diminished among older men. However, major discrimination, but not everyday discrimination, was associated with depressive symptoms of older men (age 55+), with greatest depressive symptomatology among those reporting both forms of discrimination. Discussion: Everyday discrimination is a more consistent predictor, relative to major discrimination, of depressive symptoms among African American men across the lifecourse, although there were age and/or cohort differences. Findings also demonstrate the synergistic, or additive, impact of multiple forms of discrimination on mental health.

Primary Care of Adult Women: Common Dermatologic Conditions.

Dermatologic disease often presents in the primary care setting. Therefore, it is important for the primary care provider to be familiar with the presentation, diagnosis, and treatment of common skin conditions. This article provides an overview of acne, rosacea, melasma, vitiligo, alopecia, nonmelanoma, and melanoma skin cancer, dermatitis, and lichen sclerosus.

A Trial Online Educational Melanoma Program Aimed at the Hispanic Population Improves Knowledge and Behaviors.

BACKGROUND: Hispanic individuals who suffer from melanoma are diagnosed later and have a worse prognosis. Because the Hispanic population is one of the fastest growing in the United States, it is important to spread awareness of melanoma. OBJECTIVE: The study aimed to evaluate whether an online educational video about skin cancer could improve knowledge about melanoma and encourage self-skin examinations (SSE). METHODS: The authors directed Hispanic patients to an online survey, which assessed for knowledge about melanoma risk factors and prevention. This was followed by a 5-minute online video about melanoma. A second survey was sent immediately after the video, and a third survey was sent 1 month later. All project materials were in Spanish and available online. RESULTS: Eighty-six participants completed the full experiment. After watching the online video, a significantly higher proportion of participants provided correct answers for melanoma risk factors and prevention techniques. A similar increase was seen in the number of individuals who reported performing SSEs. CONCLUSION: This study provides evidence that an online educational video targeted at the Hispanic population has potential to improve melanoma awareness. This type of intervention may lead to earlier diagnosis and better prognosis for Hispanic individuals.