Superposition mechanism as a neural basis for understanding others.

Social cognition has received much attention in fields such as neuroscience, psychology, cognitive science, and philosophy. Theory-theory (TT) and simulation theory (ST) provide the dominant theoretical frameworks for research on social cognition. However, neither theory addresses the matter of how the concepts of "self" and "other" are acquired through the development of human and nonhuman agents. Here, we show that the internal representations of "self" and "other" can be developed in an artificial agent only through the simple predictive learning achieved by deep neural networks with the superposition mechanism we herein propose. That is, social cognition can be achieved without a pre-given (or innate) framework of self and other; this is not assumed (or is at least unclear) in TT and ST. We demonstrate that the agent with the proposed model can acquire basic abilities of social cognition such as shared spatial representations of self and other, perspective-taking, and mirror-neuron-like activities of the agent's neural network. The result indicates that the superposition mechanism we propose is a necessary condition for the development of the concepts of "self" and "other" and, hence, for the development of social cognition in general.

Pharmacokinetics of ivermectin applied topically by whole-body bathing method in healthy volunteers.

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a "whole-body bathing method (WBBM)". In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole-body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole-body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment.

Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM.

A Prospective, Single-Arm, Single-Center, Case Series to Determine the Feasibility of Safe Skill Transfer for Transabdominal Preperitoneal (TAPP) Repair Utilizing a Hands-On Mentorship Model.

OBJECTIVES: It is difficult to introduce laparoscopic surgery in institutions with a small number of patients, and surgical training relies heavily on mentors to produce well-trained surgeons. The aim of this study was to determine whether implementation of a hands-on mentorship model could provide safe skill transfer for transabdominal preperitoneal (TAPP) repair. METHODS: A trainee who had no experience with TAPP repair underwent operative tutorials until the mentor judged that the trainee could carry out the operation independently. Ten patients who underwent an elective TAPP repair were prospectively enrolled in this study. RESULTS: No cases had over 5 mL of bleeding, intraoperative/postoperative complications, or recurrence. There were significant differences in operation times between the first 4 cases and the later 5 cases, except for a bilateral inguinal hernia case. CONCLUSION: A prospective, single-arm, single-center, case series showed the feasibility of safe skill transfer for TAPP repair using a hands-on mentorship model.

The first case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis.

We report a rare case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis. This appears to represent the first report of amebic intra-abdominal tumor. A 31-year-old woman presented to a local doctor with only a sensation of abdominal fullness. Abdominal computed tomography (CT) showed a huge intra-abdominal tumor in the left abdominal cavity, and she was referred to our hospital. Colonofiberscopy for detailed examination showed multiple slight, discrete ulcers in the cecum. Ameboid trophozoites were identified from biopsy specimens, and asymptomatic amebic colitis was diagnosed. Oral metronidazole (MTZ) was administered at 1500 mg/day for 10 days. CT 14 days after starting MTZ showed no change in the intra-abdominal tumor, and resection of the tumor was therefore performed. Pathological examination revealed Entamoeba histolytica with engulfed erythrocytes complicated by hemorrhagic cyst. If an intra-abdominal tumor is present and colitis is observed, amebic intra-abdominal tumor should be considered among the differential diagnoses.

Comparison of hand-assisted laparoscopic surgery and conventional laparotomy for rectal cancer: Interim results from a single center.

Minimally invasive laparoscopic surgery has become widespread and the indications for such surgery have recently been extended to various conditions, including rectal cancer. The objective of this study was to compare the clinical outcome of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy (CL) in patients with rectal cancer. Patients who underwent radical resection of stage I-III primary rectal cancer (n=111) were classified into those receiving HALS (n=57) and those receiving CL (n=54); the two groups were matched for stage and postoperative treatment. The 3-year relapse-free survival (3Y-RFS) and 3-year overall survival (3Y-OS) were calculated and compared between the two groups. Intraoperative blood loss, operating time, postoperative hospital stay and complications were also compared between the two groups. There were no significant differenceS in 3Y-RFS or 3Y-OS between the HALS and CL groups for patients with all-stage (I, II and III) rectal cancer. The mean (median) intraoperative blood loss was 344.0 (247.0) ML in the HALS group vs. 807.5 (555.5) ML in the CL group (P<0.001). The mean (median) postoperative hospital stay was 19.8 (17) and 25.5 (18.3) days, respectively (P=0.039). There were no significant differences in the operating time or the incidence of complications between the two groups. Based on these results, HALS was found to be comparable to CL regarding survival, while achieving less blood loss and a superior cosmetic outcome. However, longer follow-up is required to confirm these findings.

Breaking bad news to cancer patients in palliative care: A comparison of national cross-sectional surveys from 2006 and 2012.

OBJECTIVE: Most cancer patients experience the time when a doctor must "break the bad news" to them, a time when it is necessary for patients to call upon their self-determination to aid in the battle with cancer. The purpose of our study was to clarify the percentage of times doctors deliver bad news to patients at the end of life in each of four different situations, and to define the most common recipients of this bad news. We compare these results for two timepoints: 2006 and 2012. METHODS: The study had a national cross-sectional design consisting of self-completed questionnaires sent to all hospitals that provide cancer care. We mailed them to hospital directors in January and February of 2012, requesting a reply. The results of the same survey in 2006 were employed as a point for comparison. RESULTS: A total of 1224 questionnaires were returned during 2012. 1499 responses collected in 2006 were employed as reference data. Some hospital characteristics had changed over that interval; however, the new data obtained were representative for patients being treated in Japanese cancer care hospitals. In hospitals with 300-499, there were significant differences between 2006 and 2012 in the providing information about ("disclosure of cancer diagnosis," "therapeutic options for treatment," and "a life-prolonging treatment"). In addition, the likelihood of doctors delivering bad news to patients and family members (as opposed to family members only) at the end of life increased from 2006 to 2012. SIGNIFICANCE OF RESULTS: Our results suggest that the overall incidence of bad news being disclosed has increased, especially in hub medical institutions for cancer care. Advanced treatment options or domestic legislation may have influenced the frequency or type of bad news.

A case of prostatic abscess with malignant lymphoma involving the prostate.

Here, we report a case of prostatic abscess probably due to malignant lymphoma of the prostate. An 82-year-old man was referred to our hospital with chief complaints of urinary frequency and discomfort on urination. Antibiotics were prescribed, but the symptoms remained and intermittent fever appeared. The patient was diagnosed with prostatic abscess by computed tomography (CT). Digital rectal examination (DRE) revealed soft prostate, and thick pus was milked out from the extrameatus by prostatic massage. For drainage, we performed transurethral resection of the prostate (TURP). Drainage by TURP was successful as CT clearly showed reduction of prostatic abscess after the operation. Nevertheless, intermittent fever did not improve and the patient's general condition deteriorated. The day before the patient died, histopathological analysis showed prostatic abscess probably due to malignant lymphoma of the prostate and incidental adenocarcinoma. This is the first report of prostatic abscess with malignant lymphoma involving the prostate.

A galenical produced from Ba-Wei-Die-Huang-Wan (THC-002) provides resistance to the cold stress-induced detrusor overactivity in conscious rats.

AIMS: We determined if THC-002, a galenical produced from Ba-Wei-Die-Huang-Wan, could increase skin temperature and inhibit detrusor overactivity induced by sudden whole body cooling. Further, we determined if THC-002 could decrease expression of transient receptor potential melastatin 8 (TRPM8) channels associated with the cold responses. METHODS: Hind leg skin temperature of female 10-week-old Sprague-Dawley rats was measured by thermal imaging. Experimental rats (n = 12) were given oral 100 mg/kg THC-002 daily for one week, and controls (n = 12) were similarly treated with THC-002-free solution. Afterwards, thermal imaging and cystometric investigations of the freely moving conscious rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then transferred to a low temperature (LT, 4 ± 2°C) environment during which thermal imaging and cystometric measurements were taken at 5, 10, 20, 30, and 40 min. Afterward, the skin tissues were harvested to estimate expression levels of TRPM8 channels by immunohistochemistry and real-time reverse-transcription polymerase chain reaction. RESULTS: The RT skin temperature of THC-002-treated rats was significantly higher than controls. During the first 20 min under LT, the control rats exhibited cold stress-induced detrusor overactivity such as decreased voiding interval and bladder capacity. THC-002 partially inhibited the detrusor overactivity patterns. During the second 20 min, skin temperature was relatively stable, and the detrusor overactivity of both groups slowly disappeared. THC-002 significantly reduced expression of TRPM8 channel protein and mRNA. CONCLUSIONS: THC-002 inhibited cold stress-induced detrusor overactivity resulting from decreasing skin temperature. Therefore, THC-002 might provide resistance to cold stress-exacerbated lower urinary tract symptoms.

Functional roles of transient receptor potential melastatin 8 (TRPM8) channels in the cold stress-induced detrusor overactivity pathways in conscious rats.

AIMS: We determined if transient receptor potential melastatin 8 (TRPM8) channels are involved in the detrusor overactivity induced by menthol, or exposure to low temperature (LT). METHODS: Two days prior to cystometric investigation, the bladders of 10-week-old Sprague-Dawley rats were cannulated to measure bladder pressure. After a 20 min baseline cystometry period, the TRPM8 channel antagonist, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC), or vehicle, was administered through a jugular vein catheter (n = 6). A 90% menthol solution was sprayed onto bare leg skin once every 5 min for 20 min, and then cystometric measurements were repeated. After a 30-min recovery period, the rats were intravenously administered 0.1 µmol/kg BCTC. Five minutes later, they were again sprayed and cystometry recorded. In separate experiments, cannulated rats were intravenously administered 0.001, 0.01, or 0.1 µmol/kg BCTC (n = 6 each dose). Five minutes later, they were exposed to LT (4 ± 2°C) for 20 min of cystometry. RESULTS: Menthol spray decreased voiding interval, micturition volume, and bladder capacity in the BCTC-free rats. However after BCTC administration, these effects were prevented. Exposure to LT elicited detrusor overactivity that caused decreased voiding interval, micturition volume, and bladder capacity. However, at 0.01 and 0.1 µmol/kg, BCTC inhibited this cold stress-induced detrusor overactivity. CONCLUSIONS: Since the TRPM8 channel agonist, BCTC, inhibited detrusor overactivity in rats sprayed with the TRPM8 channel agonist, menthol, and the drug also inhibited cold stress-induced detrusor overactivity, we conclude that TRPM8 channels mediate, at least partially, detrusor overactivity elicited by exposure to LT.

The relationship between α1-adrenergic receptors and TRPM8 channels in detrusor overactivity induced by cold stress in ovariectomized rats.

PURPOSE: We studied whether cold stress induced detrusor overactivity in ovariectomized rats is associated with increased thermosensitive TRPM8 channel expression in the skin and whether the response could be inhibited by α1-adrenergic receptor blockade. MATERIALS AND METHODS: A total of 24 Sprague-Dawley® rats at postnatal week 30 were randomly selected for ovariectomy (16) or sham ovariectomy (8). Five weeks later cystometric measurements of conscious, freely moving rats were made at room temperature (mean ± SEM 28C ± 2C) for 20 minutes. Eight ovariectomized rats were intravenously administered 1.0 mg/kg naftopidil. The other 8 ovariectomized and 8 sham operated rats were given naftopidil-free vehicle. Five minutes later they were transferred to a low temperature environment (mean 4C ± 2C) and micturition patterns were again recorded. TRPM8 channel expression in lumbar skin was estimated by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: TRPM8 channel mRNA and protein in the skin of ovariectomized rats were significantly higher than in sham operated rats. At room temperature micturition parameters were similar in sham operated and ovariectomized rats. At low temperature sham operated and ovariectomized rats showed cold stress induced detrusor overactivity but increased micturition frequency and decreased bladder capacity were significantly greater in ovariectomized rats. Treatment of ovariectomized rats with naftopidil inhibited cold stress induced detrusor overactivity. CONCLUSIONS: Cold stress induced detrusor overactivity in rats with decreased estrogen is associated with TRPM8 channel up-regulation in the skin and mediated by nerve pathways using α1-adrenergic receptors.

A galenical of traditional Chinese herbal mixture (THC-002) reduces expression of tachykinin peptides within urethras of spontaneously hypertensive rats.

AIMS: We investigated expression of tachykinin peptides neurokinin A, neurokinin B, and substance P within urethras of spontaneously hypertensive rats (SHRs) and determined if a traditional Chinese herbal mixture, THC-002, decreased them. METHODS: Ten- and 40-week-old male SHRs were randomly separated into three groups (n = 12 each). Rats of one group were given orally 20 ml 0.9% NaCl solution per kg body weight daily for 1 week. One hour later, each received a similar volume of water. Rats in the second group were also given saline. One hour later, each received 20 mg THC-002 per kg body weight. The third group was untreated. The urethras were removed and separated into prostatic and non-prostatic regions and analyzed by real-time reverse transcription polymerase chain reaction (n = 6) and immunohistochemistry (n = 6). RESULTS: In 40-week-old untreated SHRs, neurokinin B mRNA and protein, and substance P mRNA in prostatic urethras were significantly higher compared to the 10-week-old ones. Neurokinin A mRNA and protein, and substance P protein of the 40-week-old saline-loaded prostatic urethras were significantly higher compared to the 40-week-old untreated ones. In 40-week-old untreated SHRs, the non-prostatic urethral neurokinin B protein was significantly higher compared to the 10-week-old ones. In 40-week-old, saline-loaded SHRs, neurokinin A protein of the non-prostatic urethras was significantly higher compared to 40-week-old the untreated ones. In 40-week-old SHRs, THC-002 significantly decreased the expression of the urethral tachykinins, except for non-prostatic urethral neurokinin A mRNA. CONCLUSIONS: Aging and saline-loading increased the expression of urethral tachykinin mRNAs and peptides. THC-002 partially decreased them.

Relationship between Toe Temperature and Lower Urinary Tract Symptoms.

OBJECTIVE: Cold stress can elicit increases in urinary urgency and frequency. We determined if there was a relationship between finger and toe temperatures and lower urinary tract symptoms (LUTS). METHODS: We studied 50 people who visited a public health management seminar. The participants were divided into two groups according to self-described sensitivity to cold stress. The cold non-sensitive (CNS) group consisted of 3 males and 20 females (66.9 ± 10.8 years old), and the cold sensitive (CS) group consisted of 4 males and 23 females (65.8 ± 8.01 years old). Each participant was assessed to determine international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and quality of life (QOL) score. They were then instructed on lifestyle changes and exercises that could improve peripheral blood flow and provide relief for their LUTS. Next, the temperatures of their middle fingers and toes were measured before and after 5-10 min of the exercises. Two weeks later, the IPSS, OABSS, and QOL scores were reassessed. RESULTS: Before exercise, the middle fingers were significantly warmer than the middle toes. Exercise had no significant effect on the middle finger temperature of either group; however, it did increase the middle toe temperature for both groups. The increase was greatest for the CS group. The CS group had higher LUTS storage symptoms than the CNS group, and these improved after 2 weeks of lifestyle changes and exercise. CONCLUSION: Improvements in lifestyle and daily exercise may be effective for LUTS in CS people.

Psychological distress and quality of life in cervical cancer survivors after radiotherapy: do treatment modalities, disease stage, and self-esteem influence outcomes?

The present study evaluated whether differences in the type of radiotherapy, disease stage, and self-esteem influence psychological distress and quality of life (QOL) among cervical cancer survivors. Sixty survivors, after radiotherapy, chemoradiotherapy, or postoperative radiotherapy for cervical cancer, participated in the study. The participants were asked to complete questionnaires during follow-up visits. The questionnaires included the Japanese version of the Hospital Anxiety and Depression Scale, the Functional Assessment of Cancer Therapy-General, and the Rosenberg Self-esteem Scale. The results indicated that psychological distress and QOL in cervical cancer survivors were not significantly different among treatment modalities and disease stage. Psychological distress and QOL differed significantly in accordance with the survivor's self-esteem. Survivors in the high self-esteem group had lower levels of anxiety and depression and higher QOL scores (emotional and social/family aspects of QOL and total QOL) than those in the low self-esteem group. Psychosocial support with consideration of a patient's self-esteem is necessary throughout and beyond radiotherapy for cervical cancer.

Relapsed prostate cancer with neuroendocrine differentiation and high serum levels of carcinoembryonic antigen without elevation of prostrate-specific antigen: a case report.

A 62-year-old man had been treated with combined androgen blockade due to cT2bN1M0 prostate cancer, and his serum prostate-specific antigen (PSA) levels decreased and remained under the level of 0.5 ng/mL during therapy. Approximately 40 months after the initial therapy, difficulty on urination and constipation developed gradually, and serum carcinoembryonic antigen (CEA) and pro-gastrin-releasing peptide (ProGRP) levels were high at this point. He underwent transrectal and transurethral biopsy of the prostate, which revealed adenocarcinoma positive for CEA and chromogranin A. He received palliative pelvic irradiation, and oral estramustine phosphate and etoposide combined therapy. Tumor markers decreased and clinical symptoms improved for several months. The patient died of encephalopathy of unknown etiology approximately 11 months after the relapse.

How do we interpret the answer "Neither" when physicians ask patients with cancer "Are you depressed or not?".

OBJECTIVES: The aim of this study was to clarify how physicians should interpret the answer "neither" to the single-question interview, "Are you depressed or not?" PATIENTS AND METHODS: Two hundred fifty-one patients with cancer were studied. The patients were directly interviewed, choosing one answer among these three: "Yes, I am depressed"; "No, I am not depressed"; or "Neither." After this, the patients completed the Hospital Anxiety and Depression Scale (HADS). The threshold of 11 or greater on HADS was used for adjustment disorder and major depressive disorder. RESULTS: All patients could reply to the single question, but 10 patients did not complete HADS. Among 83, 81 and 77 patients who answered "yes," "neither," and "no," respectively, 75 (90%), 43 (65%), and 9 (12%) patients scored 11 or more on HADS. The mean score of HADS was 12.2 in patients who answered "neither," significantly higher than that of the "no" group (p < 0.0001) and significantly lower than that of the "yes" group (p < 0.0001). CONCLUSION: Patients who answered "neither" frequently scored in a high enough range to warrant further investigation for adjustment or depressive disorder.

Spiritual needs in cancer patients and spiritual care based on logotherapy.

BACKGROUND: The suitability of Frankl's logotherapy for the spiritual care (psychotherapy) of cancer patients in Japan is suggested. Using Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp, Japanese version), the Purpose in Life test (PIL test, Japanese version), and WHO-Subjective Inventory (WHO-SUBI, Japanese version), we attempted to elucidate the complicated structure of spirituality in cancer patients in order to identify possible approaches to their spiritual care and means of evaluating such care. MATERIALS: Two hundred and ninety-eight cancer patients participated in the study. All three tests were taken at the same time, and the results were evaluated by principal component analysis. RESULTS: It was demonstrated that all the subscales employed in the present study could be represented by a two-dimensional structure (two principal components), and that the FACIT-Sp and PIL tests have similar contents. DISCUSSION: FACIT-Sp (Japanese version) is very similar in conception to the PIL test, which was prepared in accordance with logotherapy. The results suggest that this test can serve as an adequate evaluation scale for measuring the effectiveness of spiritual care based on Frankl's logotherapy.

Recurrent retroperitoneal malignant nerve sheath tumor associated with neurofibromatosis type 1 responding to carboplatin and etoposide combined chemotherapy.

A 25-year-old man was referred to our hospital with left flank pain, and computed tomography (CT) and magnetic resonance imaging (MRI) revealed large retroperitoneal masses. Physical examination revealed many café-au-lait spots and superficial neurofibromas, and a diagnosis of neurofibromatosis type 1 (von Recklinghausen's disease) was made. The tumor was resected, and the pathological diagnosis was malignant peripheral nerve sheath tumor (MPNST). Six months after the operation, lung metastases were detected. Surgical resection was incomplete, as there were too many lesions. He received four courses of chemotherapy with carboplatin and etoposide, and the metastatic lung lesions were markedly decreased. After chemotherapy, complete resection of the remaining lung lesions was performed, and there has been no recurrence to date.

[Reliability and validity of the functional assessment of chronic illness therapy-spiritual (FACIT-Sp) Japanese version in cancer patients--a preliminary study].

The reliability and validity of the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp), Japanese version, which was developed in the United States for a simple survey of QOL related to spirituality, was evaluated. The survey simultaneously covered FACIT-Sp and HADS, an anxiety and depression scale, using 64 cancer patients as the subjects of the study. In the evaluation of its intrinsic conformity, the Cronbach alpha reliability coefficient of the sub-scale ranged from 0.80 to 0.91 and the evaluation of validity by factor analysis indicated satisfactory factorial appropriateness. The correlation coefficients for the sub-scales were all below 0.7, indicating that each scale is independent. The correlation with HADS depression and anxiety scales was -0.54 and -0.56, respectively, showing that the emotional and spiritual scales are independent of each other. The findings suggest that The Japanese version of FACIT-Sp is associated with satisfactory reliability and validity and is an effective tool in the study of spirituality among cancer patients.