We have previously reported that high-temperature (42°C) culture inhibited the proliferation of human umbilical endothelial cells (HUVECs). We described how the proliferative capacity and telomere length (TL)-related parameters of HUVECs, one of somatic cells, change with culture temperature. It was speculated that a combination of cytostatic manipulations, such as anticancer treatments, and high-temperature conditions would more effectively suppress the growth of somatic cells. Therefore, we hypothesized that increasing the core body temperature (BT) as a pretreatment for cancer treatment enhances the effectiveness of cancer treatment. In the present study, various cells (HUVECs, Jurkat cells, and SLVL) were cultured under different temperature conditions (35°C, 37°C or 39°C) combined with anticancer manipulations (X-ray irradiation or addition of 1-β-D-Arabinofuranosylcytosine [Ara-C]), which resulted in changes in the proliferation rate and TL. The degree of cell proliferation inhibitory effect depended on the combination of cell type, anticancer procedure, and temperature condition. Therefore, the best therapeutic condition might be selected in advance by checking the proliferation rate of biopsied cancer cells being cultured under combinations of anticancer manipulations at altered temperature conditions.

  In 2018, we reported an epidemiological study on disease-preventive effects of habitual hot spa-bathing in the elderly in Beppu city, which has the highest number of hot spring sources in the world. In this analysis, women with diabetes mellitus were observed more often as hot spa-bathers than non-spa-bathers [odds ratio (OR): 1.238, confidence interval (CI): 1.011-1.517]. To see whether there is an apparent harmful effect of spa-bathing, complicated background diseases of women with diabetes mellitus were investigated in this study. We compared background diseases of women complicated with diabetes mellitus in spa-bathers and non-spa-bathers. Compared with non-spa-bathers, female spa-bathers with diabetes mellitus revealed a higher occurrence of cancer history (OR: 2.626, CI 1.517-4.545). The occurrence of diabetes mellitus in women with no cancer history was not significantly different between habitual spa-bathers and non-spa-bathers (OR:1.041, CI 0.837-1.293). The observed odds ratios suggest that spa-bathing associated cancer surviving promotion leads to an increasing number of diabetic women with a past history of cancer and contributes to more women with diabetes mellitus in spa-bathers rather than habitual spa-bathing promoting the pathogenesis of diabetes mellitus.

  In 2018, we reported an epidemiological study on disease-preventive effects of habitual hot spa-bathing in the elderly in Beppu city, which has the highest number of hot spring sources in the world. In this analysis, women with diabetes mellitus were observed more often as hot spa-bathers than non-spa-bathers [odds ratio (OR): 1.238, confidence interval (CI): 1.011-1.517]. To see whether there is an apparent harmful effect of spa-bathing, complicated background diseases of women with diabetes mellitus were investigated in this study. We compared background diseases of women complicated with diabetes mellitus in spa-bathers and non-spa-bathers. Compared with non-spa-bathers, female spa-bathers with diabetes mellitus revealed a higher occurrence of cancer history (OR: 2.626, CI 1.517-4.545). The occurrence of diabetes mellitus in women with no cancer history was not significantly different between habitual spa-bathers and non-spa-bathers (OR:1.041, CI 0.837-1.293). The observed odds ratios suggest that spa-bathing associated cancer surviving promotion leads to an increasing number of diabetic women with a past history of cancer and contributes to more women with diabetes mellitus in spa-bathers rather than habitual spa-bathing promoting the pathogenesis of diabetes mellitus.

  We have previously reported that high-temperature (42°C) culture inhibited the proliferation of human umbilical endothelial cells (HUVECs). We described how the proliferative capacity and telomere length (TL)-related parameters of HUVECs, one of somatic cells, change with culture temperature. It was speculated that a combination of cytostatic manipulations, such as anticancer treatments, and high-temperature conditions would more effectively suppress the growth of somatic cells. Therefore, we hypothesized that increasing the core body temperature (BT) as a pretreatment for cancer treatment enhances the effectiveness of cancer treatment. In the present study, various cells (HUVECs, Jurkat cells, and SLVL) were cultured under different temperature conditions (35°C, 37°C or 39°C) combined with anticancer manipulations (X-ray irradiation or addition of 1-β-D-Arabinofuranosylcytosine [Ara-C]), which resulted in changes in the proliferation rate and TL. The degree of cell proliferation inhibitory effect depended on the combination of cell type, anticancer procedure, and temperature condition. Therefore, the best therapeutic condition might be selected in advance by checking the proliferation rate of biopsied cancer cells being cultured under combinations of anticancer manipulations at altered temperature conditions.

Endocytoscopy (EC) is a contact-type optical endoscope that allows in vivo cellular observation during gastrointestinal endoscopy and is now commercially available not only in Japan but also in Asian, European Union, and Middle Eastern countries. EC helps conduct a highly accurate pathological prediction without biopsy. Initially, EC was reported to be effective for esophageal diseases. Subsequently, its efficacy for stomach and colorectal diseases has been reported. In this narrative review, we searched for clinical studies that investigated the efficacy of EC. EC seems to accurately diagnose gastrointestinal diseases without biopsy. Most of the studies aimed to clarify the relationship between endocytoscopic findings of gastrointestinal neoplasia and pathological diagnosis. Some studies have investigated non-epithelial lesions or diseases, such as inflammatory bowel disease or infectious diseases. However, there are few high-level pieces of evidence, such as randomized trials; thus, further studies are needed.

Endocytoscopy (EC) is a contact-type optical endoscope that allows in vivo cellular observation during gastrointestinal endoscopy and is now commercially available not only in Japan but also in Asian, European Union, and Middle Eastern countries. EC helps conduct a highly accurate pathological prediction without biopsy. Initially, EC was reported to be effective for esophageal diseases. Subsequently, its efficacy for stomach and colorectal diseases has been reported. In this narrative review, we searched for clinical studies that investigated the efficacy of EC. EC seems to accurately diagnose gastrointestinal diseases without biopsy. Most of the studies aimed to clarify the relationship between endocytoscopic findings of gastrointestinal neoplasia and pathological diagnosis. Some studies have investigated non-epithelial lesions or diseases, such as inflammatory bowel disease or infectious diseases. However, there are few high-level pieces of evidence, such as randomized trials; thus, further studies are needed.

  Although body-warming with hot spa-bathing has been proposed to exert medical therapeutic effects on certain diseases, whether body-warming has preventive and promotive effects remains unknown. To clarify this issue, an epidemiological questionnaire study regarding personal hot spa-bathing habits and disease history was carried out in Japan, where individuals engage in daily warm water bathing. Questionnaires regarding hot spa-bathing habits and disease history were randomly sent to 20,000 residents aged ≥65 years living in Beppu, a city in Japan that has the highest concentration of hot spa sources in the world. The results showed that habitual hot spa-bathing exerts preventive or promotive effects on the occurrence of certain diseases, such as hypertension (preventive) and collagen disease (promotive) in women, and cardiovascular diseases (preventive) in men. These findings suggest that habitual body warming is an effective and economical method with beneficial preventive and promotive effects on various diseases.

  Objective: Beppu city is a world-famous resort. Spa bathing has been reported to yield psychophysiological relaxation. Beppu city office planned a health-promoting tour including spa-bathing activities in Beppu for the aging population, which is growing rapidly in Japan. This tour provided spa-bathing experiences, walks through urban districts where old townscapes remain, yoga, mountain hikes and shrine visits. We investigated whether such a short tour brought about a detectable medical effect toward health promotion for the elderly.  Methods: Twenty applicants (mean age: 67.7±3.5 years; male, n＝9 [mean age, 68.9±2.9 years]; female, n＝11 [mean age, 66.7±3.7 years]), joined the tour. These voluntary participants, who were over 60 years of age, participated in a five-day-tour in Oita prefecture. Health checks were conducted on the first and last days of the tour. This tour was conducted in areas containing a gulf, mountain areas, lakeside areas, forests and shrines. Participants visited these areas during the tour.  Outcome Measures: The following parameters of the participants were measured at the beginning and end of tour: stress score, blood pressure, salivary amylase level, serum C-reactive protein level, and serum cortisol level. The results were compared and analyzed by a paired t-test and a simple regression analysis.  Results: The mean values of the following parameters (pre-intervention and post-intervention) showed significant changes after the program: stress score (43.7±8.05 and 39.4±6.57; p-value＝0.005); systolic blood pressure (131±17.8 mmHg and 125±16.2 mmHg; p＝0.018); diastolic blood pressure (73±7.3 mmHg and 70±6.6 mmHg; p＝0.016); serum cortisol (7.7±3.16 µg/dL and 6.1±1.82 µg/dL; p＝0.027). Moreover, the participants’ cortisol levels tended to converge into a normal range.   Conclusion: Tourism in a spa resort can relieve mental and physical stress, reducing blood pressure and correcting the adrenocortical function.

Purpose: The aim of present study was to investigate the endothelial function of immersion of patients with diabetes in carbon dioxide (CO2)-enriched water Methods: Sixteen diabetic patients with minor complications were immersed in CO2-enriched water for 4 weeks, and 8 patients were immersed in normal spa water for the same duration. To assess endothelial function, forearm flow-mediated dilation (FMD) was measured in those patients, and %FMD at pre-immersion was compared to that at post-immersion in CO2-enriched water. The pulse wave velocity (PWV) was also measured to determine whether vascular stiffness was affected in those patients. The percent coefficient of variation of R-R intervals was examined as CVR-R (%). All patients were medicated with antidiabetic drugs, which were not changed during the study. Results: %FMD showed no significant difference in any patients between pre- and post-CO2-enriched water bathing. However, %FMD was significantly increased in patients under 8.0% of HbA1c after CO2-enriched water bathing (p<0.05), but it was not significantly increased in patients over 8.0 of HbA1c. PWV and CVR-R (%) were significantly reduced in all patients after CO2-enriched water bathing. Conclusion: CO2-enriched water immersion had a positive effect on endothelial function, and reduced arterial wall stiffness in patients with diabetes. These findings suggest that CO2-enriched water bathing may improve microcirculation, as well as subjective symptoms, in patients with controlled diabetes.

Objective: It has been believed that hot spring bathing has therapeutic effect for certain life style-associated diseases. In addition, medical preventive effect of hot spring bathing to diseases has not been well known. In order to investigate preventive effect for life style associated diseases, we performed an epidemiological study about the relationship between personal habits of hot spring bathing and past history of diseases of aged population over 64 years old in Beppu city, which has the most hot spring fountainheads in the world. Beppu city also bear 10 kinds of spa of all except radioactivity hot spring. Materials and Methods: There are about 35,000 Beppu citizens over 64 years old. We sent the questionnaires to randomly chosen 20,000 people among them, asking the personal history of hot-spring-bathing and disease-history in Nov 2012. We received 11,146 replies filled in Jan 2013. Results: We received filled-out questionnaires from 4,706 men and 6,352 women. Forty-eight percent of the replying participants take a hot spring bath daily. The age distribution of the respondents was comparable admittably to that of all Beppu citizens registered over 64 years old. Age adjusted, hot spring user showed less rate of some diseases. The results showed that daily hot spring bathing was associated with past history of less diseases of some, such as ischemic heart disease, apoplexy, hypertension, bronchial asthma, diabetes mellitus, chronic renal disease, and depression. As for this tendency, the difference was seen among men and women (Figure 1). Moreover, the medical effect of the hot spring had the higher one where a hot spring use period is longer. Conclusion: This observation suggests that daily hot spring bathing contributes to lessen the susceptibility of some of life style associated diseases.