Frequent Emergency Department Users: Focusing Solely On Medical Utilization Misses The Whole Person.

Frequent emergency department (ED) users often have complex behavioral health and social needs. However, policy makers often focus on this population's medical system use without examining its use of behavioral health and social services systems. To illuminate the wide-ranging needs of frequent ED users, we compared medical, mental health, substance use, and social services use among nonelderly nonfrequent, frequent, and superfrequent ED users in San Francisco County, California. We linked administrative data for fiscal years 2013-15 for beneficiaries of the county's Medicaid managed care plan to a county-level integrated data system. Compared to nonfrequent users, frequent users were disproportionately female, white or African American/black, and homeless. They had more comorbidities and annual outpatient mental health visits (11.93 versus 4.16), psychiatric admissions (0.73 versus 0.07), and sobering center visits (0.17 versus <0.01), as well as disproportionate use of housing and jail health services. Our findings point to the need for shared knowledge across domains, at the patient and population levels. Integrated data can serve as a systems improvement tool and help identify patients who might benefit from coordinated care management. To deliver whole-person care, policy makers should prioritize improvements in data sharing and the development of integrated medical, behavioral, and social care systems.

Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2.

Cellular identity in metazoan organisms is frequently established through lineage-specifying transcription factors, which control their own expression through transcriptional positive feedback, while antagonizing the developmental networks of competing lineages. Here, we have uncovered a distinct positive feedback loop that arises from the reciprocal stabilization of the tyrosine kinase ABL and the transcriptional coactivator TAZ. Moreover, we determined that this loop is required for osteoblast differentiation and embryonic skeletal formation. ABL potentiated the assembly and activation of the RUNX2-TAZ master transcription factor complex that is required for osteoblastogenesis, while antagonizing PPARγ-mediated adipogenesis. ABL also enhanced TAZ nuclear localization and the formation of the TAZ-TEAD complex that is required for osteoblast expansion. Last, we have provided genetic data showing that regulation of the ABL-TAZ amplification loop lies downstream of the adaptor protein 3BP2, which is mutated in the craniofacial dysmorphia syndrome cherubism. Our study demonstrates an interplay between ABL and TAZ that controls the mesenchymal maturation program toward the osteoblast lineage and is mechanistically distinct from the established model of lineage-specific maturation.

Expression of the high affinity IgE receptor by neutrophils of individuals with allergic asthma is both minimal and insensitive to regulation by serum IgE.

We evaluated the hypothesis that serum IgE regulates neutrophil FcepsilonRI expression in the same manner as described for other FcepsilonRI+ cells. FcepsilonRI expression by neutrophils of 40 asthma subjects and 20 control subjects did not correlate with serum IgE levels, whereas FcepsilonRI expression by basophils of the same subjects showed a highly significant correlation. The level of FcepsilonRI expression by neutrophils of both asthma and control subjects was approximately 1% of that for basophil FcepsilonRI expression. IgE+ neutrophils were minimally detectable, and FcepsilonRI alpha-subunit was not detected in Western blots of neutrophil membranes and cytosol. The neutrophil FcepsilonRI did not support anti-IgE stimulated superoxide release or IgE-induced increase in neutrophil survival. We conclude that FcepsilonRI expression by neutrophils of both asthma patients and control individuals is minimal at best and that, if present, neutrophil FcepsilonRI expression, unlike that of other human FcepsilonRI+ cells, is not regulated by serum IgE.

Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type.

Mice lacking Ren1c were generated using C57BL/6-derived embryonic stem cells. Mice homozygous for Ren1c disruption (Ren1c-/-) are born at the expected ratio, but approximately 80% die of dehydration within a few days. The surviving Ren1c-/- mice have no renin mRNA expression in the kidney, hydronephrosis, thickening of renal arterial walls, and fibrosis in the kidney. Plasma renin and angiotensins I and II are undetectable. Urinary aldosterone is 6% wild-type. They have low tail-cuff BP (84 +/- 4 versus 116 +/- 5 mmHg in +/+) and excrete large amounts of urine (5.2 +/- 0.8 ml/d, 725 +/- 34 mOsm versus 1.1 +/- 0.1 ml/d, 2460 +/- 170 mOsm in +/+). After 5 d of drinking 5% dextrose, desmopressin does not increase the osmolality of the urine in -/- mice (624 +/- 19 to 656 +/- 25 mOsm), whereas in +/+, it increases severalfold (583 +/- 44 to 2630 +/- 174 mOsm). Minipump infusion of angiotensin II to Ren1c-/- mice restores BP to wild-type level, but preexisting damage to the medulla prevents complete restoration of the ability of the kidney to concentrate urine. Heterozygous Ren1c+/- mice, in contrast, are indistinguishable from +/+ in BP, urine volume, and osmolality. Kidney renin mRNA, the number of kidney cells producing renin, and plasma renin concentration in the Ren1c+/- mice are also indistinguishable from +/+. These results demonstrate that renin is the only enzyme capable of maintaining plasma angiotensins and that renin expression in the kidney is very tightly regulated at the mRNA level.