Earlier studies from our laboratory demonstrated an insulin-mediated increase in cAMP-response element binding protein (CREB) phosphorylation. In this report, we show that insulin stimulates both CREB phosphorylation and transcriptional activation in HepG2 and 3T3-L1 cell lines, models of insulin-sensitive tissues. Insulin stimulated the phosphorylation of CREB at serine 133, the protein kinase A site, and mutation of serine 133 to alanine blocked the insulin effect.Many of the signaling pathways known to be activated by insulin have been implicated in CREB phosphorylation and activation. The ability of insulin to induce CREB phosphorylation and activity was efficiently blocked by PD98059, a potent inhibitor of mitogen-activated protein kinase kinase (MEK1), but not significantly by rapamycin or wortmannin. Likewise, expression of dominant negative forms of Ras or Raf-1 completely blocked insulin-stimulated CREB transcriptional activity. Finally, we demonstrate an essential role for CREB in insulin activation of fatty-acid synthase and fatty acid binding protein (FABP) indicating the potential physiologic relevance of insulin regulation of CREB.In summary, insulin regulates CREB transcriptional activity in insulin-sensitive tissues via the Raf 3 MEK pathway and has an impact on physiologically relevant genes in these cells.Insulin binding to its cell surface receptor results in alterations in the expression of many genes for cellular growth, differentiation, and proliferation. Specific insulin responsive elements have been identified in the promoters of several genes (1-4). Peroxisome proliferator-activated receptors and other steroid hormone receptors have been implicated in regulating gene transcription through these insulin responsive elements (2, 4, 5). In other genes, insulin responsive sites have been mapped to regions containing cAMP responsive elements (CREs) 1 and serum responsive elements (6 -9). Consistent with these findings, many insulin-regulated genes are also regulated by extracellular stimuli that modulate intracellular cAMP levels (2, 10 -17) (Table I). Previously, we demonstrated that phosphorylation of CREB was stimulated by insulin in primary rat adipocytes and HIRc cells (18,19). This observation posed an important question regarding the impact of insulin-mediated CREB phosphorylation on CREB transactivation and the post-receptor pathways activated by insulin responsible for this effect. Cyclic AMP regulates the transcription of target genes primarily through the phosphorylation of the cAMP-response element binding protein (CREB) by protein kinase A (PKA) on serine 133 (of CREB-341 or serine 119 of CREB-327) of the CREB molecule (20 -23). We demonstrated an analogous response to insulin and identified that this increase in phosphorylation was at least in part due to a decrease in nuclear protein phosphatase-2A activity. These experiments were the first to show a transient increase in CREB phosphorylation and regulation of a nuclear, serine/threonine-specific protein phosphatase in response ...

Identifying specific patient characteristics and OPAT treatment factors could facilitate OPAT process improvements to reduce the risk of OPAT complications for vulnerable patients.

Although health systems are increasingly moving toward addressing social determinants of health, social risk screening for hospitalized children is largely unexplored. We sought to determine if inpatient screening was feasible and describe the prevalence of social risk among children and caregivers, with special attention given to children with chronic conditions. METHODS: Caregivers of pediatric patients on the hospitalist service at a children's hospital in the Pacific Northwest completed a social risk survey in 2017. This survey was used to capture items related to caregiver demographics; socioeconomic, psychosocial, and household risks; and adverse childhood experiences (ACEs). Charts were reviewed for child demographics and medical complexity. Results were tabulated as frequency distributions, and analyses compared the association of risk factors with a child's medical complexity by using x 2 tests. RESULTS: A total of 265 out of 304 (87%) caregivers consented to participate. One in 3 families endorsed markers of financial stress (eg, difficulty paying for food, rent, or utilities). Forty percent experienced medical bill or insurance troubles. Caregiver mental health concerns were prevalent, affecting over one-third of all respondents. ACEs were also common, with 38% of children having at least 1 ACE. The presence of any ACE was more likely for children with chronic conditions than those without. CONCLUSIONS: We found that social risk screening in the inpatient setting was feasible; social risk was uniformly common and did not disproportionately affect those with chronic diseases. Knowing the prevalence of social risk may assist in appropriate alignment of interventions tiered by social complexity.

Nonreimbursable CC work by OPAT providers prevented readmissions and ER visits and helped facilitate appropriate healthcare use. The value of pediatric OPAT involvement in patient care would have been underestimated based on reimbursable ID consultations and clinic visits alone.

Women with DM have a more significant abnormality in poststasis ELT than do men with DM as compared with sex-specific counterparts without DM.