Dynamic multi-site phosphorylation by Fyn and Abl drives the interaction between CRKL and the novel scaffolding receptors DCBLD1 and DCBLD2.

Discoidin, CUB, and LCCL domain containing 2 (DCBLD2) is a neuropilin-like transmembrane scaffolding receptor with known and anticipated roles in vascular remodeling and neuronal positioning. DCBLD2 is also up-regulated in several cancers and can drive glioblastomas downstream of activated epidermal growth factor receptor. While a few studies have shown either a positive or negative role for DCBLD2 in regulating growth factor receptor signaling, little is known about the conserved signaling features of DCBLD family members that drive their molecular activities. We previously identified DCBLD2 tyrosine phosphorylation sites in intracellular YxxP motifs that are required for the phosphorylation-dependent binding of the signaling adaptors CRK and CRKL (CT10 regulator of kinase and CRK-like). These intracellular YxxP motifs are highly conserved across vertebrates and between DCBLD family members. Here, we demonstrate that, as for DCBLD2, DCBLD1 YxxP motifs are required for CRKL-SH2 (Src homology 2) binding. We report that Src family kinases (SFKs) and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while SFKs and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. Using high-performance liquid chromatography coupled with tandem mass spectrometry, we quantified phosphorylation at several YxxP sites in DCBLD1 and DCBLD2, mapping site-specific preferences for SFKs and Abl. Together, these data provide a platform to decipher the signaling mechanisms by which these novel receptors drive their biological activities.

Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis.

OBJECTIVE: To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis. DATA SOURCES: MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations. STUDY SELECTION AND DATA EXTRACTION: The search was limited to randomized controlled trials (RCTs) reporting human outcomes. Data extracted included the following: study design, population, setting, intervention, control, outcomes related to psychosis and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool. DATA SYNTHESIS: After assessment, 16 of 235 studies were included; 11 articles reported comparisons between active drug and placebo, whereas 5 compared clozapine and an active comparator. Placebo-controlled trials demonstrated benefit for clozapine (n = 2) and pimavanserin (n = 2), with no firm benefits observed for quetiapine (n = 4) or olanzapine (n = 3). Comparative studies demonstrated improved efficacy in symptom scores when clozapine or comparator agent (n = 2, quetiapine; n = 1, olanzapine; n = 1, risperidone; and n = 1, ziprasidone) was assessed alone. However, no comparator data suggest that one agent is better than another, and none are yet available for pimavanserin. Overall risk of bias across all studies was moderate to high. CONCLUSIONS: Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.

Functional foods: How functional are they? A case report of supplement-induced psychosis.

There is rising evidence of patients' use of alternative and complementary medicine. The percentage of the U.S. population who used at least one dietary supplement increased from 42% in 1988-1994 to 53% in 2003-2006. We present a case of an Asian female in her 40s, with no previous psychiatric illness, who presented to the emergency room following a brief psychotic episode, during which she self-amputated the tips of her fingers, after using multivitamins and herbal supplements including ginseng, gui yuan rou (Chinese herb), astaxanthin, goji (Chinese fruit), selenium, saw palmetto, grape seed extract, citrus bioflavanoid, lutein (zeaxantin), resvexatrol, sun chlorella, spirulina powder, phytoceramides, phytoestrogen, glucosatrin, bromelain plus, and American bee pollen. Comprehensive laboratory workup, drug screening, and diagnostic imaging were negative. Vital signs were stable. Other than the amputated finger tips, the remainder of her physical examination was unremarkable. Her mental status improved significantly after treatment with risperidone 1 mg twice daily, during a five-day psychiatric hospitalization. This case draws attention to the fact that supplements have the potential of producing frank psychosis and require close monitoring and study by physicians.

Well-being Content Inclusion in Pharmacy Education Across the United States and Canada.

Objective. To describe the landscape of well-being content inclusion across schools and colleges of pharmacy in the United States and Canada through identification of content implementation, incorporation, and assessment.Methods. A cross-sectional survey was distributed to all accredited schools and colleges of pharmacy in the United States (n=143) and Canada (n=10). Survey questions included curricular and cocurricular timing, frequency, assessment strategies, and support for well-being initiatives, using a framework of eight dimensions (pillars) of wellness to categorize content.Results. Descriptive data analyses were applied to 99 completed surveys (65%), 89 (62%) in the United States and 10 (100%) in Canada. Well-being content was most prevalent within the cocurricular realm and incorporated into didactic and elective more than experiential curricula. The most content came from intellectual, emotional, and physical pillars, and the least content came from financial, spiritual, and environmental pillars. Less than 50% of schools and colleges of pharmacy include well-being within their strategic plans or core values. Funding is primarily at the level of the university (59%) or the school or college of pharmacy (59%). Almost half of respondents reported inclusion of some assessment, with a need for more training, expertise, and standardization.Conclusion. Survey results revealed a wide range of implementation and assessment of well-being programs across the United States and Canada. These results provide a reference point for the state of well-being programs that can serve as a call to action and research across the Academy.

The Role of Pharmacy Education in Mitigating Weight Bias.

Two-thirds of American adults are labeled as overweight or obese by current body mass index weight status categories. Individuals categorized as overweight or obese are at risk of weight bias and, subsequently, poorer health care experiences and outcomes. However, schools and colleges of pharmacy may not be providing robust education or training to student pharmacists on weight bias, assessment of their own bias, or how to address and mitigate weight bias against patients. This commentary explores the impact of weight bias on patient care and how efforts can be advanced to recognize and address weight bias in pharmacy education and pharmacy practice to provide optimal care to patients of all sizes.

Electronic structure and TDDFT optical absorption spectra of silver nanorods.

Density functional theory calculations are employed to determine optimized geometries and excitation spectra for small pentagonal silver nanorods Ag(n), with n = 13, 19, 25, 31, 37, 43, 49, 55, 61, and 67 in various charge states. The asymptotically correct SAOP functional is utilized in the excitation calculations. Silver nanorods exhibit a sharp longitudinal excitation that results from a mixture of orbital transitions; the wavelength for this excitation depends linearly on the length of the nanorod. The broad transverse excitation arises from multiple excited states. A particle-in-a-box model is employed to explain the linear dependence of the longitudinal excitation wavelength on nanorod length.