[Objectives] The aim of this study was to evaluate the changes in serum brain-derived neurotrophic factor (BDNF) concentrations during 15 min of combined hot bath and bicycle ergometer endurance exercise in healthy young men.  [Methods] The experiment was conducted in a parallel design. The subjects were 10 healthy men (aged 23.7±0.8 years). The experimental group performed a combination of head-out water immersion (HOI) at 40°C and bicycle ergometer exercise (40°C HOI-ex), while the control group performed only HOI at 40°C (40°C HOI). After 30 min of rest, 40°C HOI-ex or 40°C HOI was performed for 15 min, followed by a 30 min recovery period. During the experiment, heart rate, blood pressure, and core temperature (esophageal temperature) were continuously measured. Blood samples were collected at four time points: after rest, immediately after intervention, 15 min after recovery, and 30 min after recovery. Serum BDNF, P-selectin, platelet count, hemoglobin, hematocrit, plasma cortisol, and lactic acid were then measured.  [Results] A significant increase in serum BDNF concentrations was observed immediately after intervention and 15 min after recovery in the 40°C HOI-ex group compared with the values taken after resting. No changes in serum BDNF concentrations were observed in the 40°C HOI group. Core temperatures significantly increased immediately after intervention, 15 min after recovery, and 30 min after recovery compared with resting for both 40°C HOI-ex and 40°C HOI groups, with between-group differences. Platelet counts were unchanged in both 40°C HOI and 40°C HOI-ex groups. A significant increase in P-selectin was observed immediately after intervention and 15 min after recovery in the 40°C HOI-ex group compared with when at rest. No changes in P-selectin were observed in 40°C HOI.  [Discussion] The combination of hyperthermia and exercise can increase serum BDNF in a short time of 15 min by an additive effect, and the increase in serum BDNF in this study may be platelet-derived.

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

  [Objectives] The aim of this study was to evaluate the changes in serum brain-derived neurotrophic factor (BDNF) concentrations during 15 min of combined hot bath and bicycle ergometer endurance exercise in healthy young men.  [Methods] The experiment was conducted in a parallel design. The subjects were 10 healthy men (aged 23.7±0.8 years). The experimental group performed a combination of head-out water immersion (HOI) at 40°C and bicycle ergometer exercise (40°C HOI-ex), while the control group performed only HOI at 40°C (40°C HOI). After 30 min of rest, 40°C HOI-ex or 40°C HOI was performed for 15 min, followed by a 30 min recovery period. During the experiment, heart rate, blood pressure, and core temperature (esophageal temperature) were continuously measured. Blood samples were collected at four time points: after rest, immediately after intervention, 15 min after recovery, and 30 min after recovery. Serum BDNF, P-selectin, platelet count, hemoglobin, hematocrit, plasma cortisol, and lactic acid were then measured.  [Results] A significant increase in serum BDNF concentrations was observed immediately after intervention and 15 min after recovery in the 40°C HOI-ex group compared with the values taken after resting. No changes in serum BDNF concentrations were observed in the 40°C HOI group. Core temperatures significantly increased immediately after intervention, 15 min after recovery, and 30 min after recovery compared with resting for both 40°C HOI-ex and 40°C HOI groups, with between-group differences. Platelet counts were unchanged in both 40°C HOI and 40°C HOI-ex groups. A significant increase in P-selectin was observed immediately after intervention and 15 min after recovery in the 40°C HOI-ex group compared with when at rest. No changes in P-selectin were observed in 40°C HOI.  [Discussion] The combination of hyperthermia and exercise can increase serum BDNF in a short time of 15 min by an additive effect, and the increase in serum BDNF in this study may be platelet-derived.

[Objective] To clarify the utilization of characteristics and reactions of acupuncture points, and the frequency of using acupuncture points in acupuncture and moxibustion treatment in Japan.[Methods] We conducted a questionnaire survey involving members of the Japan Society for Oriental Medicine and those of the Japan Society of Acupuncture Course in Universities. The contents of the questions included age, sex, profession, length of clinical experience of acupuncture/moxibustion, treatment method, utilization of characteristics and reactions of acupuncture points, and frequency of using acupuncture points in both acupuncture and moxibustion treatment.[Results] The number of valid questionnaires was 59 (59 for acupuncture treatment and 50 for moxibustion treatment). The respondents were as follows : average age of 52 ± 12 years, 45 males and 14 females, 13 medical doctors and 46 acupuncturists, clinical experience of 21.1 ± 11.5 years. Most practitioners utilized ill ness-specific features of acupuncture points, de qi, and reactions they feel with their needling and pressing hands. Ten acupuncture points were used in 50% of patients in acupuncture treatment, and ST 36 and SP 6 were the most frequently used. On the other hand, no single acupuncture point was used in more than 50% of patients in moxibustion treatment. Thirteen acupuncture points were used in 30% of patients in moxibustion treatment, and BL 23, SP 6, and ST 36 were the most frequently used.[Conclusion] Our survey clarified the usage of acupuncture points in acupuncture and moxibustion treatment in Japan.

STUDY DESIGN: Prospective cohort imaging study. PURPOSE: This study aimed to evaluate lumbar sagittal alignment and range of motion (ROM) using radiographs in a large asymptomatic cohort and identify sex-based differences and age-related changes in the subjects. OVERVIEW OF LITERATURE: Several researchers have tried to establish normal alignment and kinematic behavior of the lumbar spine, using plain radiographs. Few studies have employed a large and sex-and age-balanced cohort. METHODS: Total 627 healthy volunteers (at least 50 males and 50 females in each age decade, from the 3rd to the 8th decade) underwent whole spine radiography in the standing position; lumbar spine radiography was performed for all subjects in the recumbent position. Lumbar lordosis (LL, T12–S1) and ROM during flexion and extension were measured using a computer digitizer. RESULTS: The mean LL was 36.8°±13.2° in the recumbent position and 49.8°±11.2° in the standing position. The LL was greater in the standing position than in the recumbent position; further, LL was higher in females as compared to that in males. Local lordosis at each disk level increased incrementally with distal progression through the lumbar spine in both the positions. Local lordosis at L4–S1 was 29.8°±8.0° in the recumbent position and 34.2°±8.3° in the standing position and occupied 85.1% and 70.8% of the total LL, respectively. However, local lordosis in the standing position decreased with age at L2–3, L3–4, and L4–5 levels. Total lumbar ROM (T12–S1) decreased with age. The ROM in females was higher than that in males. CONCLUSIONS: We established the standard value and age-related changes in the lumbar alignment and ROM in each age decade in asymptomatic subjects. These data will be useful and provide the normal values for comparison in clinical practice to identify sex-based differences and age-related changes.
Animals ; Cohort Studies ; Female ; Healthy Volunteers ; Humans ; Lordosis ; Male ; Posture ; Prospective Studies ; Radiography ; Range of Motion, Articular ; Reference Values ; Spine

Proteases play important roles in parasite development and host parasite interactions. The protease of Kudoa spp. has been recognized as a key factor of severe proteolysis of fish muscle post-mortem; however, there is little information available regarding the protease of Kudoa (K.) septempunctata, which was recently identified as a cause of food poisoning in humans. The present study was conducted to isolate and characterize proteases to elucidate the type of protease contained in the parasite and determine the optimal pH for protease activity. We confirmed the cysteine protease and metalloprotease produced by K. septempunctata. While the cysteine protease showed optimal activity at pH 5 that decreased rapidly with increasing pH, the optimal activity of metalloprotease was pH 7, and it remained stable from pH 6 to pH 8. These results indicate that the pH of cysteine protease is not proper for fish muscle postmortem, and that metalloprotease can act in human intestines. Overall, the present study provides important information that improves our understanding of the role of protease physiology and the subsequent food poisoning caused by K. septempunctata.
Cysteine Proteases ; Foodborne Diseases ; Host-Parasite Interactions ; Humans ; Hydrogen-Ion Concentration ; Intestines ; Parasites ; Peptide Hydrolases* ; Physiology ; Proteolysis

STUDY DESIGN: A retrospective study. PURPOSE: To examine the effectiveness of using an electrodiagnostic technique as a new approach in the clinical diagnosis of extraforaminal stenosis at L5-S1. OVERVIEW OF LITERATURE: We introduced a new effective approach to the diagnosis of extraforaminal stenosis at the lumbosacral junction using the existing electrophysiological evaluation technique. METHODS: A consecutive series of 124 patients with fifth lumbar radiculopathy were enrolled, comprising a group of 74 patients with spinal canal stenosis and a second group of 50 patients with extraforaminal stenosis at L5-S1. The technique involved inserting a pair of needle electrodes into the foraminal exit zone of the fifth lumbar spinal nerves, which were used to provide electrical stimulation. The compound muscle action potentials from each of the tibialis anterior muscles were recorded. RESULTS: The distal motor latency (DML) of the potentials ranged from 11.2 to 24.6 milliseconds in patients with extraforaminal stenosis. In contrast, the DML in patients with spinal canal stenosis ranged from 10.0 to 17.2 milliseconds. After comparing the DML of each of the 2 groups and at the same time comparing the differences in DML between the affected and unaffected side of each patient, we concluded there were statistically significant differences (p<0.01) between the 2 groups. Using receiver operating characteristic curve analysis, the cutoff values were calculated to be 15.2 milliseconds and 1.1 milliseconds, respectively. CONCLUSIONS: This approach using a means of DML measurement enables us to identify and localize lesions, which offers an advantage in diagnosing extraforaminal stenosis at L5-S1.
Action Potentials ; Constriction, Pathologic* ; Diagnosis* ; Diagnostic Techniques and Procedures ; Electric Stimulation ; Electrodes ; Humans ; Muscles ; Needles ; Radiculopathy ; Retrospective Studies ; ROC Curve ; Spinal Canal ; Spinal Nerves ; Spinal Stenosis

Objective: We examined the effects of ontokyu (warm tube moxibustion) medical treatment of GB33 and SP6 on young women with a chilly constitution (‘Hie’ symptoms). Methods: The subjects were 13 female university students (mean age: 20.7± 1.3years). They were assigned to either a GB33 group or an SP6 group in consideration of height for the determinate method by the discriminant analysis of Sakaguchi et al. After a one-week pre-observation period, 1 or 2 ontokyu treatments (Choan NEO, Yamasho) twice a week for four weeks were conducted. The follow-up period was two weeks. Effects of the therapy were evaluated using an original questionnaire (‘Hie’ diary), which consisted of six categorical scales of 14 symptoms and Visual Analogue Scale (VAS) of the severity of ‘Hie’. Results: Three subjects dropped out before 1st week therapy among the 13 subjects, so the number of subjects in both groups became five. There was no significant difference between the 2 groups in terms of age, height, weight, BMI, VAS, and total score for 14 symptoms at the baseline. There was no interaction between the groups for VAS or total score for the 14 symptoms. For both groups, no significant changes could be found in VAS during the intervention period and follow-up period compared with that during the pre-observation period. Although the total score for the 14 symptoms in both groups decreased gradually from the start of intervention for the GB33 group, it significantly decreased in after the 3rd and 4th weeks therapy compared with that in the pre-observation period. For the SP6 group, it significantly decreased in after the 4th week therapy and the 2nd week after finished therapy. For each item of the 14 symptoms, the GB33 group showed significant differences in stiff neck and shoulders and feeling thirsty when their scores between the pre-observation period and the intervention period were compared. In addition, the SP6 group showed a significant difference in stiff neck and shoulders, feeling thirsty, and nervousness when their scores between the pre-observation period and the intervention period were compared. Specifically, stiff neck and shoulders for the GB33 group was significantly reduced in the 1st and 2nd weeks after finished therapy, and feeling thirsty showed significant reduction in after the 3rd and 4th weeks therapy. On the other hand, for the SP6 group, stiff neck and shoulders significantly decreased in after the 2nd and 4th weeks therapy and the 1st and 2nd after finished therapy, as did feeling thirsty in the 4th week therapy and in the 2nd week after finished therapy, as well as becoming nervous in after the 1st, 2nd and 4th weeks therapy. Conclusion: It was suggested that ontokyu medical treatment to GB33 and SP6 for young women with a chilly constitution did not appear to exacerbate the severity of ‘Hie’ after reductions in air temperature, while improving the total score for 14 symptoms similarly.

Purpose: Escitalopram has been inadequately evaluated in cancer patients. Here, we report two patients with advanced cancer who benefited from escitalopram for depression. Case 1: A man aged in his 50s had postoperative recurrence of rectal cancer. He was diagnosed with a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). The score of the Hamilton Rating Scale for Depression (HAMD-17) was 20 points. He began treatment with 10 mg/day of escitalopram. His symptoms began to improve at about 14 days, and the HAMD-17 score was 4 points at 23 days, suggesting a marked improvement. Case 2: A woman aged in her 50s had cancer of the external auditory canal. She was diagnosed with a major depressive episode according to DSM-IV-TR. The score of HAMD-17 was 26 points. She began treatment with 10 mg/day of escitalopram. Her symptoms began to improve at 15 days, and the HAMD-17 score at 28 days was 13 points, suggesting a marked improvement. In both cases, serious side effects, clear exacerbation of depression, and withdrawal syndrome due to acute drug deprivation associated with worsening of the symptoms were not noted. Conclusion: Escitalopram is considered a useful drug for depression in patients with advanced cancer.

When patients hospitalized in a palliative care unit die, particularly when their deaths were not peaceful ones, we, as health professionals, feel distressed, senses of helplessness and defeat, and even regret. However, busy daily clinical practice usually does not allow us to express these feelings. After going through such an experience repeatedly, your self-efficacy may be reduced and you could feel burned out. In this study, through the experience of coping with the death of a liver cancer patient who died of necrotizing fasciitis resulted from bedsore, a death conference was organized for us, health professionals who had been directly concerned with the patient, to discuss questions, conflicts, and dilemmas that arose when we provided care and express feelings that had been repressed. And other participants in the conference, who had not been directly concerned with the patient, gave their affirmative views. The conferences served to: (1) promote mutual understanding, trustful relationships, and teamwork among us, (2) increase our awareness of palliative care, and (3) allow us to cope with stress and prevent us from feeling burned out. These effects are considered to help implement improved health care. In the former part of the conference remarks were divided into three categories, (1) regret, (2) questions, conflicts, and dilemmas, and (3) senses of helplessness and defeat, and in the latter part affirmative views were mainly stated.