Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where baseline (BST) levels >20 ng/mL are a minor criterion for diagnosis. Whereas clonal myeloid neoplasms are rare, the common cause for elevated BST is the genetic trait hereditary alpha-tryptasemia (HαT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HαT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HαT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from over-expression of replicated TPSAB1 loci encoding canonical α-tryptase protein due to co-inheritance of a linked over-active promoter element. Modeling BST levels based upon TPSAB1 replication number we generate new individualized clinical reference values for the upper limit of 'normal'. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (e.g., >100 ng/mL) which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within 'normal' limits for certain individuals with HαT.
The Westlawn Partnership for a Healthier Environment (WPHE) is a longstanding group of community stakeholders that was formed over a decade ago to identify, prioritize, and address environmental health (EH) concerns in a low‐income, predominantly African American, urban neighborhood, which faces a disproportionate burden of EH risks, particularly asthma. Launched by the University of Wisconsin‐Milwaukee College of Nursing, which established a nurse‐managed health center within the community 30 years ago, WPHE utilized the Protocol of Assessing Community Excellence in Environment Health methodology to develop, implement, and sustain the partnership. WPHE implemented programs for Healthy Homes, Healthy Day Cares, and bicycling, and made system and infrastructure changes within the community to address the top identified EH concerns: indoor and outdoor air pollution, mold exposure, access to safe and healthy food, and pesticide exposure. WPHE's efforts have resulted in significant local, state, and national policy impacts to promote environmental justice. This brief report shares how the partnership was formed, its priorities, major activities and accomplishments, and insights into sustaining a community‐based EH partnership, including recommendations for the key role that public health nurses can play to promote environmental justice.
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