A Research Agenda for the Assessment and Management of Acute Behavioral Changes in Elderly Emergency Department Patients.

INTRODUCTION: Agitation, mental illness, and delirium are common reasons for older adults to seek care in the emergency department (ED). There are significant knowledge gaps in understanding how to best screen older adults for these conditions and how to manage them. In addition, in areas where research has been performed, implementation has been slow. A working group convened to develop a set of high-priority research questions that would advance the understanding of optimal management of older adults with acute behavioral changes in the ED. This manuscript is the product of a breakout session on "Special Populations: Agitation in the Elderly" from the 2016 Coalition on Psychiatric Emergencies' first Research Consensus Conference on Acute Mental Illness. METHODS: Participants were identified with expertise in emergency medicine (EM), geriatric EM, and psychiatry. Background literature reviews were performed prior to the in-person meeting in four key areas: delirium; dementia; substance abuse or withdrawal; and mental illness in older adults. Input was solicited from all participants during the meeting, and questions were iteratively focused and revised, voted on, and ranked by importance. RESULTS: Fourteen questions were identified by the group with high consensus for their importance related to the care of older adults with agitation in the ED. The questions were grouped into three topic areas: screening and identification; management strategies; and the approach to delirium. CONCLUSION: It is important for emergency physicians to recognize the spectrum of underlying causes of behavioral changes, have the tools to screen older adults for those causes, and employ methods to treat the underlying causes and ameliorate their symptoms. Answers to the identified research questions have great potential to improve the care of older adults presenting with behavioral changes.

Can emergency medicine practitioners predict disposition of psychiatric patients based on a brief medical evaluation?

OBJECTIVE: Emergency medicine practitioners (EMPs) often provide 'medical clearance' before evaluation by a psychiatry practitioner (PP). We set out to determine the level of agreement between EMP impression and disposition as determined by PPs. PATIENTS AND METHODS: This was a prospective observational study in an urban tertiary teaching hospital emergency department. We collected data from February to April 2011. We used a convenience sample of patient encounters evaluated by EMPs and subsequent referral for psychiatric evaluation. We asked EMPs whether they thought the patients would be admitted or discharged following psychiatric evaluation, and if discharged, whether to outpatient psychiatric follow-up or to no follow-up. EMPs were asked to base their opinion upon their general impression following their brief medical evaluation. They were not given guidelines on which to base their decision. The EMPs were blind to PP decisions. The κ-statistic was used to calculate agreement between the EMP's impression and disposition decision by the PP. We excluded patients who were acutely intoxicated, in police custody, or lived in an extended care facility. RESULTS: We included 156 patient encounters over the study period and had complete data for 152 encounters. Of these, 86 (55%) were admitted, 46 (30%) were discharged with no specific psychiatric follow-up, and 20 (13%) were discharged with a follow-up plan. EMPs predicted the exact disposition in 77/152 (51%) cases (κ=0.264, 95% confidence interval 0.77-0.333). Agreement was higher for admitted patients, with EMPs predicting inpatient admission for 57/86 (66%) of these patients. Other factors associated with higher agreement scores were years in emergency medicine practice by the EMP and suicidal ideation by the patient. CONCLUSION: EMPs did not reliably predict psychiatric disposition decisions based on clinical 'gestalt'. Future research will focus on clinical guidelines to help EMPs better independently assess need for emergency psychiatric services.

Plant root distributions and nitrogen uptake predicted by a hypothesis of optimal root foraging.

CO(2)-enrichment experiments consistently show that rooting depth increases when trees are grown at elevated CO(2) (eCO(2)), leading in some experiments to increased capture of available soil nitrogen (N) from deeper soil. However, the link between N uptake and root distributions remains poorly represented in forest ecosystem and global land-surface models. Here, this link is modeled and analyzed using a new optimization hypothesis (MaxNup) for root foraging in relation to the spatial variability of soil N, according to which a given total root mass is distributed vertically in order to maximize annual N uptake. MaxNup leads to analytical predictions for the optimal vertical profile of root biomass, maximum rooting depth, and N-uptake fraction (i.e., the proportion of plant-available soil N taken up annually by roots). We use these predictions to gain new insight into the behavior of the N-uptake fraction in trees growing at the Oak Ridge National Laboratory free-air CO(2)-enrichment experiment. We also compare MaxNup with empirical equations previously fitted to root-distribution data from all the world's plant biomes, and find that the empirical equations underestimate the capacity of root systems to take up N.

The psychopharmacology of agitation: consensus statement of the american association for emergency psychiatry project Beta psychopharmacology workgroup.

Agitation is common in the medical and psychiatric emergency department, and appropriate management of agitation is a core competency for emergency clinicians. In this article, the authors review the use of a variety of first-generation antipsychotic drugs, second-generation antipsychotic drugs, and benzodiazepines for treatment of acute agitation, and propose specific guidelines for treatment of agitation associated with a variety of conditions, including acute intoxication, psychiatric illness, delirium, and multiple or idiopathic causes. Pharmacologic treatment of agitation should be based on an assessment of the most likely cause of the agitation. If agitation results from a delirium or other medical condition, clinicians should first attempt to treat the underlying cause instead of simply medicating with antipsychotics or benzodiazepines.

T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS as a new TCR signalosome component.

Stimulation of the T cell antigen receptor (TCR) induces formation of a phosphorylation-dependent signaling network via multiprotein complexes, whose compositions and dynamics are incompletely understood. Using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics, we investigated the kinetics of signal propagation after TCR-induced protein tyrosine phosphorylation. We confidently assigned 77 proteins (of 758 identified) as a direct or indirect consequence of tyrosine phosphorylation that proceeds in successive "signaling waves" revealing the temporal pace at which tyrosine kinases activate cellular functions. The first wave includes thymocyte-expressed molecule involved in selection (THEMIS), a protein recently implicated in thymocyte development but whose signaling role is unclear. We found that tyrosine phosphorylation of THEMIS depends on the presence of the scaffold proteins Linker for activation of T cells (LAT) and SH2 domain-containing lymphocyte protein of 76 kDa (SLP-76). THEMIS associates with LAT, presumably via the adapter growth factor receptor-bound protein 2 (Grb2) and with phospholipase Cγ1 (PLC-γ1). RNAi-mediated THEMIS knock-down inhibited TCR-induced IL-2 gene expression due to reduced ERK and nuclear factor of activated T cells (NFAT)/activator protein 1 (AP-1) signaling, whereas JNK, p38, or nuclear factor κB (NF-κB) activation were unaffected. Our study reveals the dynamics of TCR-dependent signaling networks and suggests a specific role for THEMIS in early TCR signalosome function.

Childhood asthma, air quality, and social suffering among Mexican Americans in California's San Joaquin Valley: "Nobody talks to us here".

Nearly one in five Mexican American children residing in California's San Joaquin Valley (the Valley) in 2007 had an asthma attack at some point in their life. Numerous epidemiological studies have suggested that compared with other ethnic groups and Latino subgroups residing in the United States, Mexican origin children have the lowest rates of pediatric asthma. Ethnographic research conducted in central California, however, suggests otherwise. Known for its agricultural produce, extreme poverty, and poor air quality, the Valley is a magnet for the Mexican immigrant farm worker population. We conducted an exploratory ethnographic study to examine health disparities, social suffering, and childhood asthma in the Valley. Many Valley residents believe that their children's health concerns are being ignored. Open-ended interviews uncovered a largely rural community suffering not only from the effects of childhood asthma but the inability to have their experiences taken seriously.

The stimulation of mitogenic signaling pathways by N-POMC peptides.

The N-terminal fragment of pro-opiomelancortin (POMC) has been shown previously to act as an adrenal mitogen. However, little is known about the molecular mechanisms by which mitogenesis is stimulated, although it has been shown that N-POMC(1-28) stimulates the ERK pathway in human H295R cells. We have investigated signaling stimulated by N-POMC(1-28) and N-POMC(1-49) in the mouse Y1 cell line and found that both peptides stimulate ERK phosphorylation with maximal stimulation being achieved within 5min. Similar results were observed for both MEK and c-Raf phosphorylation, although N-POMC(1-49) stimulated the phosphorylation of Akt more robustly than N-POMC(1-28). We also investigated the expression of tyrosine kinase receptors in adrenal cells. PCR utilizing degenerate primers was performed on cDNA from both Y1 cells and rat adrenal tissue. Sequencing of 114 clones from each cDNA population revealed the expression of a number of receptors, several of which have not been described previously in the adrenal.

Evidence of a possible role for Lys-gamma3-MSH in the regulation of adipocyte function.

Lys-gamma3-MSH is a melanocortin peptide derived from the C-terminal of the 16 kDa fragment of POMC. The physiological role of Lys-gamma3-MSH is unclear, although it has previously been shown that, although not directly steroidogenic, it can act to potentiate the steroidogenic response of adrenal cortical cells to ACTH. This synergistic effect appears to be correlated with an ability to increase the activity of hormone sensitive lipase (HSL) and therefore the rate of cholesterol ester hydrolysis. Ligand binding studies have suggested that high-affinity binding sites for Lys-gamma3-MSH exist in the adrenal gland and a number of other rat tissues that express HSL, including adipose, skeletal muscle and testes. To investigate the hypothesis that Lys-gamma3-MSH may play a wider role in cholesterol and lipid metabolism, we tested the effect of Lys-gamma3-MSH on lipolysis, an HSL-mediated process, in 3T3-L1 adipocytes. In comparison with other melanocortin peptides, Lys-gamma3-MSH was found to be a potent stimulator of lipolysis. It was also able to phosphorylate HSL at key serine residues and stimulate the hyperphosphorylation of perilipin A. The receptor through which the lipolytic actions of Lys-gamma3-MSH are being mediated is not clear. Attempts to characterise this receptor suggest that either the pharmacology of the melanocortin receptor 5 in 3T3-L1 adipocytes is different from that described when expressed in heterologous systems or the possibility that a further, as yet uncharacterised, receptor exists.