Comparison of response options and actual symptom frequency in the Japanese version of the Edinburgh Postnatal Depression Scale in women in early pregnancy and non-pregnant women.

BACKGROUND: The positive predictive rate of the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) is lower than those of other versions. This study aimed to confirm whether the EPDS Japanese version reflects actual symptom frequency and to examine the possibility of improving the positive predictive rate. METHODS: This is a methodological study aimed at improving the positive predictive value of EPDS. The participants were 63 non-pregnant and 382 pregnant women. They answered the 10 questions of the Japanese version of the EPDS and reported the specific number of days as the frequency. The EPDS score (EPDS-S) and the frequency score (FREQ-S) were calculated for three factors of emotion: anhedonia, anxiety, and depression. RESULTS: The positive rates of the EPDS-S and FREQ-S in pregnant women were 6% and 8%, respectively, which were lower than those in non-pregnant women (17%). On comparing the EPDS-S with the FREQ-S, a significant underestimation of frequency was observed in approximately 3% of pregnant women. The FREQ-S showed better internal consistency than the EPDS-S. Among the factors of emotion, women tended to rate anhedonia lower in the EPDS-S than in the frequency scale. CONCLUSION: Pregnant women tended to report a lower frequency on the Japanese version of the EPDS than their actual symptom frequency, which was especially true for those with a desire to self-harm. The combined use of the FREQ-S and EPDS-S can prevent underestimation and help improve the detection rate of depression.

[Effects of strolling on the mind and autonomic activities of elderly people in the 2018 Yamaguchi Yume Flower Expo Well-being Garden based on the heart rate, blood pressure, low frequency/high frequency and mood].

AIM: In recent years in Japan, forest therapies have been implemented in various places. While the effects of such therapies have been reported in previous research papers, those of artificial gardens have not been clarified. At the 2018 Yamaguchi Yume Flower Expo, the Yamaguchi University Faculty of Medicine had the opportunity to provide a "Well-being Garden" in collaboration with the Japan Landscape Contractors Association Yamaguchi Prefecture Branch. We examined the physical and mental responses of older people who strolled in the Well-being Garden. METHODS: Participants were 158 people ≥ 65 years old. Pre-and post-stroll interviews were conducted, and the heart rate, blood pressure, and autonomic nervous activities were measured. RESULTS: After strolling in the garden, the heart rate significantly decreased from 76.1±12.9 to 73.9±11.8/min (p<0.01), and both the systolic and diastolic blood pressure significantly decreased from 142.5±24.4 to 139.4±24.1 mmHg and from 83.7±12.0 to 81.5±11.9 mmHg, respectively (p<0.01). The ralue of low frequency/high frequency (LF/HF) after strolling in the garden came closer to the standard one than before, both in the participants with much tension and with less tension. In the post-stroll interview, 74 reported feeling very good, and 84 felt good. CONCLUSIONS: These results suggested that strolling in the Well-being Garden positively influenced the physical and mental condition of the participants.

Imipramine ameliorates pain-related negative emotion via induction of brain-derived neurotrophic factor.

Depression-like behavior is often complicated by chronic pain. Antidepressants including imipramine (IMI) are widely used to treat chronic pain, but the mechanisms are not fully understood. Brain-derived neurotrophic factor (BDNF) is a neuromodulator that reduces depression by regulating synaptic transmission. We aimed to characterize the antidepressant effects of IMI without analgesia based on BDNF (trkB)-mediated signaling and gene expression in chronic pain. A chronic constriction injury (CCI) model was constructed in Sprague-Dawley (SD) rats. IMI (5 mg/kg, i.p.) was administered from day 10 after CCI. The pain response was assessed using the paw withdrawal latency (PWL) and depression was judged from the immobility time in a forced swim test. Anti-BDNF antibody, K252a, or 5,7-dihydroxytryptamine (5,7-DHT) were used to examine the antidepressant effects of imipramine. Changes in pERK1/2 (immunohistochemistry), 5-HT and BDNF (ELISA), and BDNF mRNA (RT-PCR) were measured in the anterior cingulate cortex (ACC), rostral ventromedial medulla (RVM), and spinal cord. After CCI, rats showed decreased PWL and increased immobility time. A low dose of IMI reduced the immobility time without having analgesic effects. This antidepressant effect was reversed by anti-BDNF antibody, K252a, and 5,7-DHT. IMI reduced excessive activation of pERK1/2 associated with decreased pCREB and BDNF mRNA, and these changes were reversed by 5,7-DHT. These results show that IMI reduces pain-related negative emotion without influencing pain and that this effect is diminished by denervation of 5-HT neurons and by anti-BDNF treatment. IMI also normalizes derangement of ERK/CREB coupling, which leads to induction of BDNF. This suggests a possible interaction between 5-HT and BDNF.

Hypothermia at 35 °C reduces the time-dependent microglial production of pro-inflammatory and anti-inflammatory factors that mediate neuronal cell death.

BACKGROUND: Therapeutic hypothermia protects neurons after severe brain damage. This effect has been mainly achieved at the core temperatures of 32-34 °C; however, the optimum temperature of therapeutic hypothermia is not fully defined. Here we studied whether hypothermic culture at 35 °C had the same effects on the decrease of time-dependent expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, and nitric oxide (NO) by stimuli-activated microglia as that at 33 °C, as determined in our previous reports, and whether these factors directly induced neuronal cell death. METHODS: We determined the levels of cytokines and NO produced by microglia cultured with adenosine triphosphate (ATP), a toll-like receptor (TLR)2 agonist (N-palmitoyl-S-(2,3-bis(palmitoyloxy)-(2R,S)-propyl)-(R)-cysteinyl-seryl-(lysyl)3-lysine, Pam(3)CSK(4)), or a TLR4 agonist (lipopolysaccharide) under mild hypothermic (33 °C), minimal hypothermic (35 °C), and normothermic (37 °C) conditions. We also determined the viability of rat neuronal pheochromocytoma PC12 cells treated with recombinant TNF-α or IL-10 or (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3, an NO donor). RESULTS: Production of TNF-α, as well as that of IL-10 and NO were decreased by minimal hypothermia at 1.5-6, and 24-48 h, respectively, compared with normothermia, although some effects were diminished as compared with those by mild hypothermia. Exposure to TNF-α, IL-10, and NOR3 caused the death of PC12 cells in a concentration-dependent manner after 24 h. CONCLUSION: Hypothermic culture at 35 °C decreased the production of early-phase TNF-α and late-phase IL-10 and NO from ATP- and TLR-activated microglia as observed at 33 °C, albeit with diminished effects. Moreover, these factors caused the death of neuronal cells in a concentration-dependent manner. These results suggest that the attenuation of microglial production of TNF-α, IL-10, and NO by therapeutic hypothermia leads to the inhibition of neuronal cell death. Minimal hypothermia at 35 °C may be sufficient to elicit neuroprotective effect.

The Utility of a Novel Stacked Microvascular Imaging for Enhanced Detection of Fibrosis in Chronic Liver Diseases.

OBJECTIVE: Ultrasonographic imaging plays a primary role to detect fibrotic changes in patients with chronic liver disease (CLD). To enhance detectability of fibrosis in its early stage, we developed a novel stacked microvascular imaging (SMVI) that enables continuous visualization of fibrotic changes in intrahepatic vessels. METHODS: SMVI was produced by accumulating 3-5 seconds of high-definition color images in tilted-scan mode. An SMVI score was devised by quantitating three hallmark vascular changes in liver fibrosis in 0-2 grades (total 0-6): narrowing, caliber irregularity, and tortuosity. To evaluate the clinical utility of the SMVI score, 469 well-defined CLD patients were enrolled and subgrouped by the stage of liver fibrosis defined based on elastography: F0-1Low, F0-1High, F2, F3, and F4. The diagnostic performance of the SMVI score was compared to conventional B-mode liver morphology score and various laboratory test markers of fibrosis. RESULTS: Unlike conventional microvascular imaging that relies on a single image, SMVI enabled an undisrupted view of intrahepatic vessels for easy detection of fibrotic changes. SMVI detected microvascular narrowing in 92% at stage F0-1High. While detection rates for caliber irregularity and tortuosity were low at early stages but increased proportionately in advanced stages. Multiple logistic regression analysis revealed that SMVI score was most accurate in distinguishing F0-1Low from F0-1High cases compared to B-mode or laboratory test scores. CONCLUSION: SMVI provides enhanced vascular images of liver fibrosis in CLD, especially in its early stage. The SMVI score can be used as a primary tool for determining fibrotic stages in CLD.

Temperature-related effects of adenosine triphosphate-activated microglia on pro-inflammatory factors.

BACKGROUND: Therapeutic hypothermia protects neurons after severe brain injury. Activated microglia produce several neurotoxic factors, such as pro-inflammatory cytokines and nitric oxide (NO), during neuron destruction. Hence, suppression of microglial release of these factors is thought to contribute partly to the neuroprotective effects of hypothermia. After brain insults, adenosine triphosphate (ATP) is released from injured cells and activates microglia. Here, we examined the acute effects of temperature on ATP-activated microglial production of inflammatory factors, and the possible involvement of p38 mitogen-activated protein kinase (p38) underlying such effects. METHODS: Microglia were cultured with ATP at 33, 37, and 39°C, or with ATP in the presence of a p38 inhibitor, SB203580, at 37°C. Cytokine and NO levels, and p38 activation were measured. RESULTS: Compared to 37°C, TNF-α was reduced at 33°C and augmented at 39°C for 1.5 h. IL-6 was reduced at 33°C for 6 h. NO was reduced at 33°C, but augmented at 39°C for 6 h. p38 was reduced at 33°C for 1 min. SB203580 inhibited ATP-induced TNF-α, IL-6, and NO production. CONCLUSION: Lowering temperature rapidly reduced p38 activation and the subsequent p38-regulated production of pro-inflammatory cytokines and NO in ATP-activated microglia, suggesting that attenuation of early phase inflammatory responses via suppression of p38 in microglia is one possible neuroprotective mechanism of therapeutic hypothermia. Temperature elevation increased TNF-α and NO production in these cells. These temperature-dependent changes imply that monitoring of TNF-α and NO in the cerebrospinal fluid during the early phase might be useful as biomarkers for responses to therapeutic hypothermia and hyperthermia.

The Effects of an Artificial Garden on Heart Rate Variability among Healthy Young Japanese Adults.

Spending time in nature might positively influence mental health by inducing a relaxed state. Recently, gardens have been created on hospital rooftops in Japan to help inpatients recover from various physical and mental aliments. However, there is little evidence regarding any positive physiological effects of artificial gardens designed for health. The purpose of this study was to assess the psychological and cardiovascular responses incited by artificial natural environments. Japanese university students (n = 38) participated in a one-group pretest post-test experiment conducted at the Yamaguchi Flower Expo in Japan in October 2018, designed to assess whether exposure to four environments (forest, flowers, ocean, and artificial garden for health) influenced heart rate variability measures. After pretesting to determine baseline measurements, participants completed a circuit through the four natural environments. Following circuit completion, post-testing determined that the low frequency/high frequency ratio was significantly lower in the overall sample and the four areas had similar influences on heart rate variability. Findings suggest that exposure to nature by walking through natural areas and in rooftop artificial gardens might enhance the balance between the sympathetic and parasympathetic nervous systems.

Longitudinal study of a health education program for Japanese women in menopause.

In this longitudinal intervention study, a 6 week health education program consisting of lectures and exercises was implemented for 39 Japanese menopausal women. The effects of the program were assessed by measuring their exercise participation, climacteric symptoms, and quality of life immediately before, 6 weeks after, and 1 year after the program. The Simplified Menopausal Index was used to assess the climacteric symptoms and the Medical Outcomes Study 36-Item Short-Form Health (SF-36) Survey was used to assess the quality of life. Significant improvements were observed in the subscale score for general health perception and the summary score for the physical component summary in the SF-36 Survey. Favorable results also were found for women without a previous exercise habit before the program but who participated in regular exercise 1 year after the program. No improvements were observed in the climacteric symptoms. We concluded that our program was effective for menopausal women in spite of the intervention period being relatively short.