Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation.

In addition to the hallmark accumulation of amyloid and hyper-phosphorylation of tau, brain changes in Alzheimer's disease are multifactorial including inflammation, oxidative stress, and metal dysregulation. Metal chelators have been explored as a less well known approach to treatment. One chelator currently being developed is deferoxamine (DFO), administered via the intranasal (IN) route. In the current study, APP/PS1 amyloid mice were treated with a chronic, low dose of IN DFO, subjected to a rigorous battery of behavior tests, and the mechanism of action was examined. Mice were treated 3x/week with 0.24 C IN DFO for 18 weeks from 36 to 54 weeks of age, 4 weeks of behavior tests were performed that included both working and reference memory, anxiolytic and motor behaviors, and finally brain tissues were analyzed for amyloid, protein oxidation, and other proteins affected by DFO. We found that IN DFO treatment significantly decreased loss of both reference and working memory in the Morris and radial arm water mazes (p < 0.05), and also decreased soluble Aß40 and Aß42 in cortex and hippocampus (p < 0.05). Further, IN DFO decreased activity of GSK3ß, and led to decreases in oxidative stress (p < 0.05). These data demonstrate that low doses of IN DFO can modify several targets along the multiple pathways implicated in the neuropathology of Alzheimer's, making it an attractive candidate for the treatment of this heterogeneous disease.

In search of compassion: a new taxonomy of compassionate physician behaviours.

BACKGROUND: Compassion has been extolled as a virtue in the physician-patient relationship as a response to patient suffering. However, there are few studies that systematically document the behavioural features of physician compassion and the ways in which physicians communicate compassion to patients. OBJECTIVE: To develop a taxonomy of compassionate behaviours and statements expressed by the physician that can be discerned by an outside observer. DESIGN: Qualitative analysis of audio-recorded office visits between oncologists and patients with advanced cancer. SETTING AND PARTICIPANTS: Oncologists (n = 23) and their patients with advanced cancer (n = 49) were recruited in the greater Rochester, New York, area. The physicians and patients were surveyed and had office visits audio recorded. MAIN OUTCOME MEASURES: Audio recordings were listened to for qualitative assessment of communication skills. RESULTS: Our sensitizing framework was oriented around three elements of compassion: recognition of the patient's suffering, emotional resonance and movement towards addressing suffering. Statements of compassion included direct statements, paralinguistic expressions and performative comments. Compassion frequently unfolded over the course of a conversation rather than being a single discrete event. Additionally, non-verbal linguistic elements (e.g. silence) were frequently employed to communicate emotional resonance. DISCUSSION AND CONCLUSIONS: This study is the first to systematically catalogue instances of compassionate communication in physician-patient dialogues. Further refinement and validation of this preliminary taxonomy can guide future education and training interventions to facilitate compassion in physician-patient interactions.

Movement of cyantraniliprole in plants after foliar applications and its impact on the control of sucking and chewing insects.

BACKGROUND: Given the physical properties of insecticides, there is often some movement of these compounds within crop plants following foliar application. In this context, movement of two formulations of cyantraniliprole, an anthranilic diamide, was characterized for translocation to new growth, distribution within a leaf and penetration through the leaf cuticle. RESULTS: Upward movement of cyantraniliprole to new plant growth via the xylem was confirmed using (14) C-radiolabeled cyantraniliprole and from Helicoverpa zea mortality on tomato leaves that had not been directly treated. Within a leaf there was significant acropetal movement (base to apex) of cyantraniliprole, but no significant basipetal movement (apex to base). Translaminar movement, the ability of a compound to penetrate the leaf cuticle, was demonstrated in a variety of plants, both with and without the use of adjuvants, by treating only the adaxial surface of the leaf and measuring control of diamondback moth (Plutella xylostella), green peach aphid (Myzus persicae) and sweetpotato whitefly (Bemisia tabaci) exposed in clip cages to the untreated abaxial surface. CONCLUSION: The plant mobility and plant protection of cyantraniliprole is discussed with implications for use in insect resistance management and integrated pest management programs.

"Speaking-for" and "speaking-as": pseudo-surrogacy in physician-patient-companion medical encounters about advanced cancer.

OBJECTIVE: To examine using audio-recorded encounters the extent and process of companion participation when discussing treatment choices and prognosis in the context of a life-limiting cancer diagnosis. METHODS: Qualitative analysis of transcribed outpatient visits between 17 oncologists, 49 patients with advanced cancer, and 34 companions. RESULTS: 46 qualifying companion statements were collected from a total of 28 conversations about treatment choices or prognosis. We identified a range of companion positions, from "pseudo-surrogacy" (companion speaking as if the patient were not able to speak for himself), "hearsay", "conflation of thoughts", "co-experiencing", "observation as an outsider", and "facilitation". Statements made by companions were infrequently directly validated by the patient. CONCLUSION: Companions often spoke on behalf of patients during discussions of prognosis and treatment choices, even when the patient was present and capable of speaking on his or her own behalf. PRACTICE IMPLICATIONS: The conversational role of companions as well as whether the physician checks with the patient can determine whether a companion facilitates or inhibits patient autonomy and involvement. Physicians can reduce ambiguity and encourage patient participation by being aware of when and how companions may speak on behalf of patients and by corroborating the companion's statement with the patient.