PLDT (planarian light/dark test): an invertebrate assay to quantify defensive responding and study anxiety-like effects.

BACKGROUND: Planarians, like rodents, instinctively spend more time in dark versus light environments when given a choice. This behavioral phenomenon is called negative phototaxis, which may reflect defensive responding related to an anxiety-like phenotype. NEW METHOD: We propose a planarian light/dark test, designated PLDT, to predict anxiogenic- or anxiolytic-like effects. Experimentally, we placed a planarian at the midline of a Petri dish, containing test compound or water, that was split evenly into light and dark compartments and determined time spent in the light over 10min. RESULTS: A clinically-approved benzodiazepine agonist (clorazepate; 10µM) increased time spent in the light whereas an inverse benzodiazepine agonist (FG-7142; 1, 10µM) produced the opposite response. Fluoxetine (1µM) or ethanol (1%), as well as the 'bath salt' cathinone S-mephedrone (300µM), enhanced time spent in the light. Planarians exposed to predator (frog) odor spent more time in the dark. COMPARISON WITH EXISTING METHODS: The light/dark box (LDB) test in rodents is used to screen putative medications for possible anxiolytic and anxiogenic effects. Our results showing that time spent in the light by planarians is enhanced by common anxiety-relieving drugs (e.g. benzodiazepine agonist, ethanol, fluoxetine) and decreased by anxiogenic substances (e.g. predator odor, benzodiazepine inverse agonist) reveal directionally similar effects in the established (LDB) and new (PLDT) assays. CONCLUSION: Our data identify the PLDT as a cost-effective, invertebrate assay for quantifying the effects of practically any water-soluble substance on defensive responding and for studying and teaching anxiety-like responses in a living organism.

The Association of Types of Training and Practice Settings with Doctors' Empathy and Patient Enablement among Patients with Chronic Illness in Hong Kong.

BACKGROUND: The increase in non-communicable disease (NCD) is becoming a global health problem and there is an increasing need for primary care doctors to look after these patients although whether family doctors are adequately trained and prepared is unknown. OBJECTIVE: This study aimed to determine if doctors with family medicine (FM) training are associated with enhanced empathy in consultation and enablement for patients with chronic illness as compared to doctors with internal medicine training or without any postgraduate training in different clinic settings. METHODS: This was a cross-sectional questionnaire survey using the validated Chinese version of the Consultation and Relational Empathy (CARE) Measure as well as Patient Enablement Instrument (PEI) for evaluation of quality and outcome of care. 14 doctors from hospital specialist clinics (7 with family medicine training, and 7 with internal medicine training) and 13 doctors from primary care clinics (7 with family medicine training, and 6 without specialist training) were recruited. In total, they consulted 823 patients with chronic illness. The CARE Measure and PEI scores were compared amongst doctors in these clinics with different training background: family medicine training, internal medicine training and those without specialist training. Generalized estimation equation (GEE) was used to account for cluster effects of patients nested with doctors. RESULTS: Within similar clinic settings, FM trained doctors had higher CARE score than doctors with no FM training. In hospital clinics, the difference of the mean CARE score for doctors who had family medicine training (39.2, SD = 7.04) and internal medicine training (35.5, SD = 8.92) was statistically significant after adjusting for consultation time and gender of the patient. In the community care clinics, the mean CARE score for doctors with family medicine training and those without specialist training were 32.1 (SD = 7.95) and 29.2 (SD = 7.43) respectively, but the difference was not found to be significant. For PEI, patients receiving care from doctors in the hospital clinics scored significantly higher than those in the community clinics, but there was no significant difference in PEI between patients receiving care from doctors with different training backgrounds within similar clinic setting. CONCLUSION: Family medicine training was associated with higher patient perceived empathy for chronic illness patients in the hospital clinics. Patient enablement appeared to be associated with clinic settings but not doctors' training background. Training in family medicine and a clinic environment that enables more patient doctor time might help in enhancing doctors' empathy and enablement for chronic illness patients.

Activation of STAT3 by specific Galpha subunits and multiple Gbetagamma dimers.

The hematopoietic-specific G(q) subfamily members, Galpha(16) and Galpha(14) proteins have recently been shown to be capable of stimulating the signal transducer and activator of transcription 3 (STAT3) as well as STAT1. In the present study we examined whether this activation was STAT-member specific as well as determining the possible involvement of Gbetagamma dimers. Despite clear stimulation of STAT3, the constitutively active mutants of Galpha(16) (Galpha(16)QL) and Galpha(14) (Galpha(14)QL) failed to induce the phosphorylation of several STAT family members, including STAT2, STAT4 and STAT5 in human embryonic kidney 293 cells. On the other hand, transient expression of specific combinations of Gbetagamma complexes induced STAT3 phosphorylation. Among the 48 combinations tested, 13 permutations of Gbetagamma stimulated STAT3 phosphorylation and all of them contain the neuronal-specific Ggamma(2), Ggamma(4), Ggamma(7) and Ggamma(9). These results suggested that the activation of STAT family members by Galpha(16) or Galpha(14) was selective and that distinct combinations of Gbetagamma complexes can also regulate the STAT signaling pathway.