Long-term clinical clerkship improves medical students' attitudes toward team collaboration.

Objectives: To examine the related factors associated with medical students' attitudes toward team collaboration. Methods: This cross-sectional study targeted medical students, residents, and doctors. A survey was conducted from 2016 to 2017 using the Japanese version of the Jefferson Scale of Attitudes Toward Interprofessional Collaboration (JeffSATIC-J), which evaluated "working relationship" and "accountability." We analyzed 2409 questionnaire responses with JeffSATIC-J items and the gender item. Analysis of variance was used for factors associated with the JeffSATIC-J score and Spearman's rank correlation coefficient for the relationship between educational intervention and the JeffSATIC-J score. Results: First-year students' scores were the highest (F(2, 2045) = 13.42 to 18.87, p < .001), and female students' scores were significantly higher than those of male students (F(1, 2045) = 21.16 to 31.10, p < .001). For residents' scores, the institution was not a significant variable. Female "accountability" scores were significantly higher than those of males (F (1,108) = 4.95, p = .03). Gender was not a significant variable for doctors' scores. Sixth-year students' scores were significantly correlated with the length of clinical clerkship (r(5)=.78 to .96, p<.05), with the exception of females' "working relationship" scores. The medical school with the highest JeffSATIC-J scores had the longest clinical clerkship in the community. Conclusions: These results indicate that long-term clinical clerkship in the community at higher grades is important in improving medical students' attitudes toward team collaboration. A qualitative study is required to confirm our findings.

Effect of stress coping ability and working hours on burnout among residents.

BACKGROUND: Burnout among residents leads to interruptions in training and even to exit from programs. Despite the implementation of working hour restrictions in the U.S. in 2013, the high rate of burnout remains a serious problem. Therefore, we analyzed Japanese residents' burnout, training conditions, and associated factors, especially stress coping ability, which could become an evidence base for creating guidelines of programs and working environments. METHODS: In total, 37 teaching hospitals were randomly selected, and all residents in the third and fifteenth months of a residency program at these hospitals were targeted for this research. We analyzed the residents' burnout rates, associated factors, and interactions using response data from a self-administered questionnaire consisting of the Japanese versions of the Maslach Burnout Inventory (MBI) and the Sense of Coherence (SOC) scale, as well as items asking about their training environments, gender, and age. RESULTS: Overall, 48 (49.5%) of 97 residents in 18 teaching hospitals (62 and 35 in the third and fifteenth months, respectively), whose average working hours were 63.3 h per week, were judged as having burnout, among whom, 33 (53.2%) and 15 (42.9%) had burnout in the third and fifteenth months, respectively. Logistic regression analysis indicated that working hours and 10 items on the SOC scale (SOC10) were significant factors of burnout. Two-way analysis of variance revealed that working hours was a significant variable for the MBI-emotional exhaustion score and SOC10 in the third and fifteenth months, respectively. Regarding the MBI-cynicism and professional efficacy scores, the SOC10 was a significant variable in both the third and fifteenth months. In addition, the high SOC group (SOC10 > 45) showed higher personal efficacy under longer working hours. CONCLUSION: About half of the Japanese residents were judged as having burnout as early as the third month of training under regulations of working 40 h per week. Individual stress coping ability and working hours were found to be significant factors for burnout. Residents with high stress coping ability exhibited more personal efficacy with more working experiences, which suggests that the SOC scale could be a valuable tool to help foster a suitable training environment.

The enhancement effect of estradiol on contextual fear conditioning in female mice.

Several studies have reported regulatory effects of estrogens on fear conditioning in female rodents. However, these studies used different doses, durations, and/or administration methods, and reported inconsistent results. To clarify the effect of estrogen on fear conditioning, we investigated the effects of different doses and durations of estradiol administration on freezing behavior during contextual fear conditioning in ovariectomized (OVX) mice. In Experiment 1, OVX ICR mice received a single subcutaneous (s.c.) injection of either oil vehicle (control, 0.1 ml sesame oil) or varied doses (0.5 µg/0.1 ml, 5 µg/0.1 ml, or 50 µg/0.1 ml) of 17ß-estradiol-3-benzoate (EB). Fear conditioning was conducted two days post-EB treatment, and the mice were tested for the learned fear response the following day. In Experiment 2, OVX female mice received an s.c. implantation of a Silastic capsule (I.D. 1.98 × 20.0 mm) containing either vehicle or varied doses (0.05 µg/0.1 ml, 0.5 µg/0.1 ml, 5 µg/0.1 ml, 50 µg/0.1 ml) of EB. Two weeks after implantation, fear conditioning was conducted. During the tests conducted 24 h after conditioning, the high dose EB group showed longer freezing times in both experiments, and lower locomotor activity compared to the control or lower dose groups. In Experiment 3, serum estradiol concentrations of the mice that were treated like those in Experiment 2, were measured; the serum levels of estradiol increased linearly according to the dose of EB administered. The results suggest that mice treated with a high dose of EB exhibit enhanced fear learning, regardless of treatment duration. As a woman's vulnerability to emotional disorders increases in the peripregnancy period, during which estrogen levels are high, the results from the high-dose EB groups may be important for understanding the hormonal mechanisms involved in these disorders.

Effects of diethylstilbestrol exposure during gestation on both maternal and offspring behavior.

Endocrine disruption during gestation impairs the physical and behavioral development of offspring. However, it is unclear whether endocrine disruption also impairs maternal behavior and in turn further contributes to the developmental and behavioral dysfunction of offspring. We orally administered the synthetic non-steroidal estrogen diethylstilbestrol (DES) to pregnant female C57BL/6J mice from gestation day 11-17 and then investigated the maternal behavior of mothers. In addition, we examined the direct effects of in utero DES exposure and the indirect effects of aberrant maternal behavior on offspring using the cross-fostering method. In mothers, endocrine disruption during gestation decreased maternal behavior. In addition, endocrine disruption of foster mother influenced anxiety-related behavior and passive avoidance learning of pups regardless of their exposure in utero. The influence of DES exposure in utero, irrespective of exposure to the foster mother, was also shown in female offspring. These results demonstrate the risks of endocrine disruptors on both mother as well as offspring and suggest that developmental deficits may stem from both in utero toxicity and aberrant maternal care.

A male-specific QTL for social interaction behavior in mice mapped with automated pattern detection by a hidden Markov model incorporated into newly developed freeware.

BACKGROUND: Owing to their complex nature, social interaction tests normally require the observation of video data by a human researcher, and thus are difficult to use in large-scale studies. We previously established a statistical method, a hidden Markov model (HMM), which enables the differentiation of two social states ("interaction" and "indifference"), and three social states ("sniffing", "following", and "indifference"), automatically in silico. NEW METHOD: Here, we developed freeware called DuoMouse for the rapid evaluation of social interaction behavior. This software incorporates five steps: (1) settings, (2) video recording, (3) tracking from the video data, (4) HMM analysis, and (5) visualization of the results. RESULTS: Using DuoMouse, we mapped a genetic locus related to social interaction. We previously reported that a consomic strain, B6-Chr6C(MSM), with its chromosome 6 substituted for one from MSM/Ms, showed more social interaction than C57BL/6 (B6). We made four subconsomic strains, C3, C5, C6, and C7, each of which has a shorter segment of chromosome 6 derived from B6-Chr6C, and conducted social interaction tests on these strains. DuoMouse indicated that C6, but not C3, C5, and C7, showed higher interaction, sniffing, and following than B6, specifically in males. COMPARISON WITH EXISTING METHOD: The data obtained by human observation showed high concordance to those from DuoMouse. The results indicated that the MSM-derived chromosomal region present in C6-but not in C3, C5, and C7-associated with increased social behavior. CONCLUSIONS: This method to analyze social interaction will aid primary screening for difference in social behavior in mice.

Genetic mapping of social interaction behavior in B6/MSM consomic mouse strains.

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than approximately 12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test.

Effect of ER-beta gene disruption on estrogenic regulation of anxiety in female mice.

It has been shown that long-term estrogen treatment in gonadectomized female mice increases anxiety levels. On the other hand, a recent study has reported that estrogen may down-regulate the levels of anxiety by acting through estrogen receptor (ER) beta. In the present study, we investigated the role of ER-beta in the regulation of anxiety levels in female mice after long-term estrogen treatment. Gonadectomized ER-beta knockout (betaERKO) female mice and their wild type (betaWT) littermates were implanted several different doses (experiment 1: 2.0 microg/day, experiment 2: 1.0, 0.4, 0.2 or 0.1 microg/day) of an estradiol benzoate (EB) or placebo pellet. Ten days after pellet implant, behavioral tests commenced to measure the anxiety levels (experiment 1: light-dark transition test (LDT), experiment 2: LDT, elevated plus maze test (EPM) and social investigation test (SIT)). We found that, at higher-doses, long-term treatment of EB had anxiogenic effects in both betaWT and betaERKO mice as indicated by a decrease of the time spent in the light side and the number of transitions between two sides during LDT. In contrast, several behavioral measurements indicated that the lower-doses treatment of EB might reduce the anxiety levels possibly through ER-beta. Particularly, the anxiolytic effects of EB in the SIT were more pronounced in betaWT mice than betaERKO mice. Together, the findings in the present study suggest that estrogen may have both anxiolytic and anxiogenic effects in female mice, and that ER-beta gene disruption did not affect anxiogenic regulation by estrogen in female mice, but partially affected anxiolytic regulation.

Abolition of sex-dependent effects of prenatal exposure to diethylstilbestrol on emotional behavior in estrogen receptor-alpha knockout mice.

To investigate the contribution of estrogen receptor-alpha in the effects of prenatal exposure to diethylstilbestrol on emotionality, estrogen receptor-alpha knockout heterozygous pregnant mice were orally given 0.1 microg/animal of diethylstilbestrol from gestational day 11 to 17. Emotional behavior of the offspring was assessed at 5 weeks in light-dark transition tests. Time spent in the light area was significantly decreased (i.e. decrease of emotionality) by diethylstilbestrol exposure in wild-type female mice, whereas in wild-type male mice this measurement tended to be increased (i.e. increase of emotionality) by diethylstilbestrol treatment. These sex-dependent effects of diethylstilbestrol were completely abolished in estrogen receptor-alpha knockout mice. These results suggest that the sex-dependent effects of diethylstilbestrol on emotionality are mainly produced by its action on estrogen receptor-alpha.

Activation of accessory olfactory bulb neurons during copulatory behavior after deprivation of vomeronasal inputs in male rats.

We examined whether the vomeronasal organ (VNO) is the sole receptor for pheromonal cues for male sexual behavior. Males carrying surgical removal of the VNO (VNOx) mated with stimulus females as sham-operated males, with a comparable number of mounts but a prolonged latency for ejaculation. In sham-operated males, mating increased cFos immunoreactivity in the granule and mitral cell layers of the accessory olfactory bulb and in the medial amygdala. VNOx diminished baseline as well as mating-induced cFos in the granule cell layer and in the medial amygdala; VNOx had no effect on either basal or induced cFos immunoreactivity in the mitral cell layer. Thus, during mating encounter, cFos expression in the mitral cell layer did not depend on VNO inputs. The medial amygdala may be modulated by impulses other than of mitral cell origin.

Visual and anticipatory bias in three cortical eye fields of the monkey during an adaptive decision-making task.

To examine the role of three cortical eye fields during internally guided decision-making processes, we recorded neuronal activities in the frontal eye field (FEF), supplementary eye field (SEF), and lateral intraparietal cortex (LIP) using a free-choice delayed saccade task with two synchronized targets. Although the monkeys must perform the task in a time-locked manner, they were free to choose either the receptive field (RF) target or the nonreceptive field (nRF) target to receive reward. In all three areas we found neurons with stronger activation during trials when the monkey was going to make a saccade to the RF target (RF trials) than to the nRF target (nRF trials). Modulation occurred not only during target presentation (visual bias) but also before target presentation (anticipatory bias). The visual bias was evident as an attenuated visual response to the RF stimulus in nRF trials. The anticipatory bias, however, was seen as an enhancement of pretarget activity in the RF trials. We analyzed the activity during the 500 msec before target presentation and found that 22.5% of FEF and 31.3% of LIP neurons and 49.1% of SEF neurons showed higher activity during the RF trials. To more accurately determine when each neuron started to show preferential activity, we used a new inverse interspike interval analysis procedure. Our results suggest that although all three cortical eye fields reflect attentional and intentional aspects of sensorimotor processing, SEF plays an earlier and perhaps more cognitive role in internally guided decision-making processes for saccades.