Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Increase in the left hippocampal dentate gyrus head volume after a 4-week bright light exposure in healthy participants: A randomized controlled study.

INTRODUCTION: Bright light therapy (BLT) has been used for treating seasonal affective disorder, depression and bipolar depression. However, it's precise mechanism remains unclear. Bright light exposure (BL) induces neurogenesis in the adult rat hippocampal dentate gyrus (DG). We hypothesized that BL may induce neurogenesis in the human DG as well. METHOD: A 4-week randomized controlled trial study was conducted, where healthy participants were randomly assigned to a BL group (10,000 lux) or dim light exposure group (DL group; 50 lux). Magnetic resonance imaging was performed at baseline and after 4 weeks. Longitudinal hippocampal subfield segmentation was generated via the FreeSurfer 7.1.1 hippocampal subfields module to evaluate volume of bilateral granule cell and molecular layer of the DG-head and -body. RESULTS: Our final sample size was 20, which consisted of BL group (n = 10) and DL group (n = 10). After age and sex adjustment, significant effects of time and group were detected in the left DG-head volume (p = 0.04). In the BL group, the left DG-head volume significantly increased (p = 0.004), whereas no significant volumetric change was observed in the DL group. CONCLUSIONS: This study revealed that 4-week BL significantly increased left DG-head volume in healthy participants. Thus, neurogenesis might be induced by BL in the human DG, which is a completely new mechanism of BLT.

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling.

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific Pten knockout mice as a prostate cancer model to investigate whether there is a gut microbiota-mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited prostate cancer cell proliferation, and reduced prostate Igf1 expression and circulating insulin-like growth factor-1 (IGF1) levels. In prostate cancer tissue, MAPK and PI3K activities, both downstream of the IGF1 receptor, were suppressed by Abx administration. IGF1 directly promoted the proliferation of prostate cancer cell lines DU145 and 22Rv1 in vitro. Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF1 levels. In humans, IGF1 was found to be highly expressed in prostate cancer tissue from obese patients. In conclusion, IGF1 production stimulated by SCFAs from gut microbes influences the growth of prostate cancer via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in prostate cancer prevention and treatment. SIGNIFICANCE: These results suggest that intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells.

Maternal overprotection predicts consistent improvement of self-compassion during mindfulness-based intervention and existential approach: a secondary analysis of the EXMIND study.

BACKGROUND: Recently, we showed that 4-week mindfulness-based intervention (MBI) followed by 4-week existential approach (EXMIND) was as effective for developing self-compassion as 8-week MBI. This study aims to identify the predictors to EXMIND. METHODS: Of the 63 participants who completed the EXMIND group, 60 participants had baseline, 4-week, and 8-week total scores of the Self-Compassion Scale (SCS). Of the participants, 49 were female and 11 were male, with a mean age of 48.4 years. We investigated the participants' intervention response patterns, then used analysis of variance to compared those patterns by age, gender, and the baseline scores of the Temperament Evaluation of Memphis, Pisa and San Diego Auto-questionnaire, the Temperament and Character Inventory, Mini-Mental State Examination, the Japanese Adult Reading Test, Young Mania Rating Scale, Hamilton Rating Scale for Depression, the Parental Bonding Instrument, and the Purpose in Life Test. In addition, multivariate logistic regression analysis was performed to identify any response pattern predictors. RESULTS: Participants were divided into 4 groups based on response patterns in the changes of total SCS scores of the EXMIND group. The first group consisted of 15 participants who responded positively to MBI, but negatively to the existential approach (A group). The second group consisted of 23 participants who responded negatively to MBI, but positively to the existential approach (B group). The third group consisted of 20 participants who responded positively to both MBI and the existential approach (C group). The fourth group consisted of only 2 participants who responded negatively to both MBI and the existential approach (D group). Participants who responded positively to both MBI and the existential approach (C group) reported more maternal overprotectiveness than the other participants (groups A, B, and D). CONCLUSIONS: The present findings suggest that maternal overprotection may predict consistent improvement of self-compassion during EXMIND therapy.

More Purpose in Life and Less Novelty Seeking Predict Improvements in Self-Compassion During a Mindfulness-Based Intervention: The EXMIND Study.

OBJECTIVES: Recently, a 4-week mindfulness-based intervention followed by a 4-week existential approach was found to be as effective for increasing self-compassion as an 8-week mindfulness-based intervention. The purpose of the present study was to identify the factors that predicted change in self-compassion during the 8-week mindfulness-based intervention. METHODS: Fifty-seven of the 61 completers of the 8-week mindfulness-based intervention provided baseline, 4-week, and 8-week self-compassion scale scores. The mean age of the 47 females and 10 males was 49.6 years. Pearson's correlation coefficients were generated on the associations between the change of total self-compassion scale scores from baseline to 8 weeks with age; gender; and the baseline scores on the Temperament Evaluation of Memphis, Pisa and San Diego Auto-questionnaire, Temperament and Character Inventory (TCI), Mini-Mental State Examination, Japanese Adult Reading Test, Young Mania Rating Scale, Hamilton Rating Scale for Depression, Parental Bonding Instrument, and purpose in life (PIL). Multiple regression analysis was performed to identify the predictors of the change in total self-compassion scale scores. RESULTS: Novelty seeking (TCI) was significantly and negatively associated with the change in total self-compassion scale scores, whereas the PIL scores were significantly and positively associated with the change in total self-compassion scale scores. Novelty seeking was not significantly associated with baseline, 4-week, or 8-week total self-compassion scale scores, whereas the PIL scores were significantly and positively associated with baseline, 4-week, and 8-week total self-compassion scale scores. The limitation of the present study was a relatively small number of subjects which deterred a more sophisticated analysis of the pathways involved. CONCLUSIONS: The present findings suggest that more PIL and less novelty seeking predict improvements in self-compassion during mindfulness-based interventions, although novelty seeking might substantially predict the improvement but self-compassion scale and PIL might somewhat conceptually overlap.

Existential and Mindfulness-Based Intervention to Increase Self-Compassion in Apparently Healthy Subjects (the EXMIND Study): A Randomized Controlled Trial.

Objectives: Mindfulness is a method of training the regulation of attention with non-judgmental acceptance that is linked to beneficial effects on health. The existential approach supports the uniqueness of each individual and helps to provide meaning to their lives. In this randomized controlled trial, we examined whether mindfulness-based intervention (MBI) and the existential approach could be combined sequentially and whether they operated antagonistically or cooperatively. Methods: One hundred thirty-seven participants aged 20 years or older without any severe mental disorders were randomly assigned (1:1), via an envelope method, to receive either 8-week MBI (N = 68) or 4-week MBI followed by 4-week existential approach (EXMIND) (N = 69). Participants were first allocated to a waiting-list group and subsequently randomized to the MBI group or EXMIND group. The primary outcome was self-compassion scale (SCS) total scores at 0, 4, and 8 weeks during intervention or waiting. The analyses were performed by linear mixed models for both primary and secondary outcomes following the intention-to-treat principle. Results: Both MBI and EXMIND groups had significantly increased SCS total scores compared to those of the waiting group, with mean SCS total scores of 2.3 (SD 3.0) in the MBI group and 2.1 (2.9) in the EXMIND group versus 0.3 (2.2) in the waiting group. Conclusions: Our findings suggest that MBI followed by existential approach are not antagonistic and may have cooperative effects, suggesting that EXMIND may be a useful treatment.

Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety.

BACKGROUND: Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans. OBJECTIVE: The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model. METHODS: Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test. RESULTS: Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group. CONCLUSIONS: These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects.

[Pyogenic spondylitis by Enterobacter cloacae as a postoperative complication of TURP: a case report].

We report a case of pyogenic spondylitis caused by Enterobacter cloacae as a rare complication of transurethral resection of the prostate (TURP). A 79-year-old man underwent TURP. Immediate after removal of urethral catheter on postoperative day (POD) 7, he developed high fever > 40 degrees C with increased acute inflammatory reaction. Urine and blood culture detected E. cloacae and methicillin-resistant Staplylococcus aureus. He complained of lumbago since POD 9. Two-week administration of imipenem and teicoplanin resulted in resolution of fever as well as laboratory data, so intravenous antibiotics were changed to oral gatifloxacin. However, his lumbago worsened and gait disturbance appeared. On POD 39, diagnosis of pyogenic spondylitis was finally obtained by Ga-scintigraphy and magnetic resonance imaging. Aspiration of the intervertebral disk (L4-5) revealed E. cloacae as the causative organism of pyogenic spondylitis. His condition improved after conservative treatment with teicoplanin, meropenem and ciplofloxacin for 9 weeks.