Exploring the role of empathy in prolonged grief reactions to bereavement.

Grief reactions to the bereavement of a close individual could involve empathy for pain, which is fundamental to social interaction. To explore whether grief symptoms interact with social relatedness to a person to whom one directs empathy to modulate the expression of empathy, we administered an empathy task to 28 bereaved adults during functional magnetic resonance imaging, in which participants were subliminally primed with facial stimuli (e.g., faces of their deceased or living relative, or a stranger), each immediately followed by a visual pain stimulus. Individuals' grief severity promoted empathy for the pain stimulus primed with the deceased's face, while it diminished the neural response to the pain stimulus primed with the face of either their living relative or a stranger in the medial frontal cortex (e.g., the right dorsal anterior cingulate cortex). Moreover, preliminary analyses showed that while the behavioral empathic response was promoted by the component of "longing" in the deceased priming condition, the neural empathic response was diminished by the component of "avoidance" in the stranger priming condition. Our results suggest an association between grief reactions to bereavement and empathy, in which grief symptoms interact with interpersonal factors to promote or diminish empathic responses to others' pain.

Development of the Japanese version of the Depression Literacy Scale.

BACKGROUND: Depression is a major social concern in Japan. It is therefore necessary to develop a scale in Japanese that can assess depression literacy. AIMS: The present study aimed to develop the Japanese version of the Depression Literacy Scale (D-Lit-J), and examined its validity and reliability. METHODS: Three groups were administered the D-Lit-J, including 117 first-year university English literature students, 112 first-year medical school students, and 53 psychiatrists. Among these, 112 (95.7%), 112 (100%), and 29 subjects (54.7%) returned completed questionnaires, respectively. The total D-Lit-J scores were compared between the three groups to assess known-group validity, and internal reliability was examined by calculating Cronbach's alpha coefficients. Medical students were asked to complete the questionnaire a second time, 3 weeks later (11 students did not respond), to assess the test-retest reliability using the intra-class correlation coefficient. RESULTS: The total D-Lit-J scores (mean ± SD) were 7.61 ± 4.18, 9.51 ± 4.37, and 17.7 ± 3.15, for English literature students, medical students, and psychiatrists, respectively, and there were significant differences between the three groups (p < .05). The Cronbach's alpha coefficients ranged from .800 to .834 in all students, and was .764 in psychiatrists, revealing a good internal consistency. The intra-class correlation coefficient of the scale was .769. CONCLUSIONS: The D-Lit-J showed a credible known-group validity, with good internal and test-retest reliabilities. Additional studies with a greater variety of subjects and that examine concurrent or discriminant validity will be necessary in the future.

Functional MRI and Structural Connectome Analysis of Language Networks in Japanese-English Bilinguals.

We aimed to clarify the mechanisms of neural plasticity involved in language. We hypothesized that alterations which occur in bilinguals could reflect the mechanisms of acquisition of a second language and simulate neural plasticity related to language. We compared spatial characteristics of story listening-related hemodynamic modulations and subcortical fiber networks between monolinguals and bilinguals. Participants were Japanese monolinguals and Japanese-English bilinguals whose first language was Japanese. We divided bilinguals into early and late bilinguals depending on whether the age of acquisition was before after 7 years of age. We applied intergroup analysis to investigate the following: (1) blood oxygen level-dependent response (BOLD) responses during story listening by block-based fMRI; (2) number of fibers (NOFs) between specific edges by DTI. Both bilingual samples showed larger BOLD responses (BRs) in the right putamen and bilateral superior temporal gyri compared to the Japanese monolinguals in fMRI. Late bilinguals demonstrated bigger BRs in the right anterior temporal lobe and left medial parietal lobe than early bilinguals. Early bilinguals showed a higher NOFs between the right putamen and precentral gyrus than monolinguals and late bilinguals in DTI. Late bilinguals showed a lower NOFs between the left superior temporal gyrus and supramarginal gyrus than monolinguals and early bilinguals. Early bilinguals reinforce the subcortical fiber network between the right putamen and precentral gyrus, and activate the right putamen to gain alternative language function. We conclude that these key cerebral regions and subcortical fiber networks could contribute to the neural plasticity of language.

Changes in health care-associated infection prevention practices in Japan: Results from 2 national surveys.

BACKGROUND: A national survey conducted in 2012 revealed that the rates of regular use of many evidence-based practices to prevent device-associated infections were low in Japanese hospitals. We conducted a second survey 4 years later to evaluate changes in infection prevention practices. METHODS: Between July 2016 and January 2017, the instrument used in a survey of Japanese hospitals in 2012 was sent to 1,456 Japanese hospitals. The survey assessed general hospital and infection prevention program characteristics and use of practices specific to preventing catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated pneumonia (VAP). Independent sample chi-square tests were used to compare prevention practice rates between the first and second surveys. RESULTS: A total of 685/971 (71%) and 940/1,456 (65%) hospitals responded to the first and second surveys, respectively. For CAUTI, only use of bladder ultrasound scanners (11.1%-18.1%; P < .001) increased. For CLABSI, use of chlorhexidine gluconate for insertion site antisepsis (18.5%-41.1%; P < .001), antimicrobial dressing with chlorhexidine (3.4%-7.1%; P = .001), and central line insertion bundle (22.9%-33.0%; P < .001) increased. For VAP, use of semirecumbent positioning of patients (65.0%-72.3%; P = .002), sedation vacation (31.5%-41.6%; P < .001), oscillating/kinetic beds (4.7%-8.6%; P = .002), and a collective VAP prevention bundle (24.8%-34.8%; P < .001) increased. Fewer than 50% of Japanese hospitals reported conducting CAUTI and VAP surveillance. CONCLUSIONS: Collaborative approaches and stronger incentives promoting infection prevention efforts may be warranted to further increase use of most evidence-based practices to reduce common health care-associated infections in Japan.

Systematic Consensus Building on Disaster Mental Health Services After the Great East Japan Earthquake by Phase.

OBJECTIVE: We intended to build consensus on appropriate disaster mental health services among professionals working in the area affected by the Great East Japan Earthquake. METHODS: We focused on the first 3 months after the disaster, divided into 3 phases: immediate aftermath, acute phase, and midphase. We adopted the Delphi process and asked our survey participants (n=115) to rate the appropriateness of specific mental health services in each phase and comment on them. We repeated this process 3 times, giving participants feedback on the results of the previous round. Through this process, we determined the criterion for positive consensus for each item as having the agreement of more than 80% of the participants. RESULTS: We found that the importance of acute psychiatric care and prescribing regular medication for psychiatric patients gained positive consensus in the immediate aftermath and acute phase. Counseling and psychoeducation after traumatic events or provision of information gained consensus in the acute phase and midphase, and screening of mental distress gained consensus in the midphase. CONCLUSIONS: Higher priority was given to continuous psychiatric services in the immediate aftermath and mental health activities in later phases.

Involvement of substance P in the development of cisplatin-induced acute and delayed pica in rats.

BACKGROUND AND PURPOSE: Although substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin-induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non-nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time-dependent changes in cisplatin-induced pica and the involvement of SP and NK1 receptors in this behaviour. EXPERIMENTAL APPROACH: Rats were administered cisplatin with or without a daily injection of a 5-HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin-induced expression of preprotachykinin-A (PPT-A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated. KEY RESULTS: Cisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2-5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT-A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h. CONCLUSIONS AND IMPLICATIONS: The profiles of cisplatin-induced pica in rats are similar to clinical findings for cisplatin-induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin-induced pica.

Involvement of hypothalamic cyclooxygenase-2, interleukin-1ß and melanocortin in the development of docetaxel-induced anorexia in rats.

Docetaxel, a taxane derivative, is frequently used for the treatment of advanced breast cancer, non-small cell lung cancer, and metastatic prostate cancer. Clinical reports demonstrated that docetaxel-based chemotherapy often induces anorexia, but the etiology is not completely understood. To elucidate possible mechanisms, we investigated the involvement of central interleukin (IL)-1ß, cyclooxygenase (COX)-2, and pro-opiomelanocortin (POMC) in the development of docetaxel-induced anorexia in rats. Rats received docetaxel (10mg/kg, i.p.) with or without pretreatment with selective COX-2 inhibitors, NS-398 (10 and 30 mg/kg, i.g.) or celecoxib (10 and 30 mg/kg, i.g.), and a non-selective COX inhibitor, indomethacin (10mg/kg, i.g.), then food intake was monitored for 24h after administration. We also examined expression of IL-1ß, COX-2, and POMC mRNA in hypothalamus of docetaxel-treated rats and the effect of a COX-2 inhibitor on docetaxel-induced POMC mRNA expression. Food consumption in rats was significantly decreased 24h after administration of docetaxel and anorexia was partially reversed by all COX inhibitors. Administration of docetaxel increased IL-1ß, COX-2, and POMC mRNA expression in the hypothalamus of rats. The time required to increase these gene expressions was comparable to the latency period of docetaxel-induced anorexia in rats. In addition, pretreatment with COX-2 inhibitors suppressed docetaxel-induced expression of POMC mRNA. These results suggest that IL-1ß and COX-2 mRNA expression and subsequent activation of POMC in the hypothalamus may contribute to the development of docetaxel-induced anorexia in rats.

Time-course analysis of pica in rats using an automatic feeding monitoring system.

INTRODUCTION: We have reported that pica, kaolin ingestion behavior, correlates with nausea and vomiting in rats and the amount of kaolin intake is related to the severity of symptoms. However, the time course of the behavior is still unclear, because kaolin intake has been measured 24h after administration of an emetic stimulus. It is quite difficult and troublesome to determine kaolin intake manually at short time intervals without affecting the animal's behavior. In the present study, we investigated the time course of radiation or chemotherapeutic agent-induced pica in rats using an automatic feeding monitoring system (FDM700SW). METHODS: Rats received total body X-ray irradiation (4 Gy), or i.p. administration of cisplatin (6 mg/kg) or cyclophosphamide (120 mg/kg) with or without pretreatment of 5-HT(3) receptor antagonist, granisetron (0.1mg/kg, i.p.), then their kaolin and food intake were monitored hourly for 24h after the emetic stimuli. RESULTS: Total body irradiation and i.p. injection of cisplatin or cyclophosphamide induced pica within 3h of the administration and the pica persisted for 12, 8 and 16 h after the emetic stimuli, respectively. Granisetron delayed the latency and inhibited the amount of kaolin intake. X-ray and chemotherapeutic agents induced anorexia in all rats, but anorexia was not recovered by pretreatment with granisetron. DISCUSSION: These results suggested that both the latency and the duration of pica are similar to the clinical evidence of radiation or chemotherapy-induced nausea and vomiting in human patients and this monitoring system is useful to evaluate the emetogenic potential of drugs and other medical intervention in preclinical studies.

Involvement of substance P and the neurokinin-1 receptor in radiation-induced hair loss in mice.

We investigated the involvement of substance P (SP) and the neurokinin-1 receptor (NK(1)R) in the development of radiation-induced hair loss in mice. A dose of 40 Gy of gamma irradiation induced hair loss from the 10th to at least the 60th day after irradiation. A specific NK(1)R antagonist, CP-99,994, significantly delayed radiation-induced hair loss and reduced its severity. Furthermore, gamma irradiation induced the expression of preprotachykinin-A, a precursor protein of SP, mRNA in irradiated murine skin on the 10th and 30th days after irradiation. These results indicated that gamma irradiation-induced hair loss was mediated by SP via NK(1)R.

Involvement of hypothalamic glutamate in cisplatin-induced emesis in Suncus murinus (house musk shrew).

We investigated the effect of cisplatin on glutamate release in the hypothalamus of Suncus murinus measured by brain microdialysis. Dialysis samples were collected every 20 min for 1 h before and 3 h after the cisplatin (30 mg/kg, i.p.) administration with the animals also being observed for the development of emesis. Cisplatin increased glutamate levels within 1 h and this was closely associated with the occurrence of emesis. Pretreatment with the 5-HT(3)-receptor antagonist ondansetron (2 mg/kg, i.p.) inhibited both the emesis and the increased glutamate levels. These results suggest that hypothalamic glutamate is involved in cisplatin-induced emesis in Suncus murinus.

Application of intramolecular 1,3-dipolar cyclic addition of azide and olefin; construction of (pyrrolidine-2-ylidene)glycinate and glycinamides.

Oxopropyl E-(pyrrolidine-2-ylidene)glycinamide (5c) and allyl E-(pyrrolidine-2-ylidene)glycinate (5d) were effectively synthesized from 2,3,5-tri-O-benzyl-4-O-tert-butyldimethylsilyl(TBDMS)-D-arabinal (7) using intramolecular 1,3-dipolar cyclic reaction of azide and olefin as a key reaction. These results proved this cyclic reaction should be applicable for the synthesis of various (pyrrolidine-2-ylidene)glycinate and glycinamide. In addition, the development of a synthetic route for the precursor of an unsaturated cyclic dehydro amino acid involved in azinomycins (carzinophilin) using relating glycinate, methyl E-(pyrrolidine-2-ylidene)glycinate (5a) was described.