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Investigation of a practical assessment index to capture the clinical presentation of cachexia in patients with lung cancer.
Katsushima, U, Hase, K, Fukushima, T, Kubo, T, Nakano, J, Ogushi, N, Okuno, Y, Kamisako, K, Nakanishi, K, Okazaki, Y, et al
Japanese journal of clinical oncology. 2024;(3):305-311
Abstract
OBJECTIVE Cancer cachexia constitutes a poor prognostic factor in patients with lung cancer. However, the factors associated with cancer cachexia remain unclear. This study aimed to identify factors that influence cancer cachexia in patients with lung cancer. METHODS In this retrospective observational study conducted at the Kansai Medical University, 76 patients with lung cancer were evaluated for physical function, nutritional status (Mini Nutritional Assessment-Short Form) and physical activity (International Physical Activity Questionnaire-Short Form) at the first visit to the rehabilitation outpatient clinic. The patients were divided into cachexia and noncachexia groups. The log-rank tests and Cox proportional hazards model were used to investigate the relationship between cachexia and prognosis. To examine the factors that influence cachexia, multivariate regression analysis with significant (P < 0.05) variables in the univariate logistic regression analysis was performed. Spearman's correlation analysis was performed to investigate the association between International Physical Activity Questionnaire-Short Form and performance status. RESULTS Overall, 42 patients (55.2%) had cachexia associated with survival time since their first visit to the outpatient rehabilitation clinic, even after confounders adjustment (hazard ratio: 3.24, 95% confidence interval: 1.12-9.45, P = 0.031). In the multivariate analysis, Mini Nutritional Assessment-Short Form (odds ratio: 20.34, 95% confidence interval: 4.18-99.02, P < 0.001) and International Physical Activity Questionnaire-Short Form (odds ratio: 4.63, 95% confidence interval: 1.20-17.89, P = 0.026) were identified as independent factors for cachexia. There was no correlation between International Physical Activity Questionnaire-Short Form and performance status (r = 0.155, P = 0.181). CONCLUSION Malnutrition and low physical activity were associated with cachexia in patients with lung cancer. The International Physical Activity Questionnaire-Short Form may be a useful indicator of physical activity in cachexia. Regularly assessing these factors and identifying suitable interventions for cachexia remain challenges to be addressed in the future.
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Effects of Lactococcus lactis subsp. cremoris YRC3780 daily intake on the HPA axis response to acute psychological stress in healthy Japanese men.
Matsuura, N, Motoshima, H, Uchida, K, Yamanaka, Y
European journal of clinical nutrition. 2022;76(4):574-580
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Plain language summary
The hypothalamic-pituitary-adrenal (HPA) axis is involved in the stress response and is linked to the microbiome through a number of possible mechanisms, including immune-related ones. Lactococcus lactis subsp. cremoris YRC3780 (YRC3780), a probiotic isolated from kefir, has been shown to have beneficial immune-modulatory properties. The aim of this double-blind, placebo-controlled trial, which included 27 healthy young men, was to assess sleep quality, mental health, HPA axis activity (salivary cortisol) and response to an acute stress test during/after 8 weeks of supplementation with YRC3780. At 8 weeks, salivary morning cortisol levels were significantly reduced in the probiotic compared to the placebo group. The effect on the stress test depended on whether or not participants were considered “cortisol-responders” or not. Improvements in sleep quality were seen at 6 weeks (but not at any other time points) in 1 out of 2 sleep questionnaires in the YRC3780 group, whilst no significant differences were observed in actigraphy-measured sleep efficiency. There were no differences in mood between groups, but significant improvements in general health in the probiotic group. Interestingly, no changes in the microbiome of the probiotic group were seen, suggesting that the observed effects may be mediated via the immune system.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Research indicates a bidirectional interaction between the gut microbiome and the central nervous system, affecting the functions of the brain and spinal cord.
- This clinical trial suggests that daily intake of Lactococcus lactis subsp. cremoris (YRC3780) may enhance the HPA axis response to acute psychological stress, potentially linked to a reduction in morning cortisol levels.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomized, placebo-controlled, double-blind clinical trial was conducted to investigate the influence of Lactococcus lactis subsp. cremoris (YRC3780), isolated from kefir, on stress response, sleep quality, and mental health.
Method
Twenty-seven healthy young men, with an average age of 23.5 years, and mean body mass index of 21.5 kg/m2 , were randomly assigned to either the YRC3780 group or the placebo group. Participants were administered YRC3780 or a placebo daily for 8 weeks.
Throughout the study, participants completed assessments, including the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ-28), and the Profile of Mood States 2nd Edition-Adult Short, Total Mood Disturbance subscale (POMS 2 TMD), every 2 weeks. Additionally, diurnal rhythms of HPA axis activity were assessed every 2 weeks through saliva samples collected at 2-hour intervals during the day. At the end of the 8-week supplementation period, participants underwent the Trier Social Stress Test (TSST) to evaluate the effects of daily YRC3780 intake on the HPA axis stress response. In addition, three fecal samples were collected to analyse the gut microbiome (on the last day of baseline, and at 4 and 8 weeks).
A total of 27 out of 33 subjects (81%) completed the study, with six participants withdrawing without providing explanations.
Results
The primary findings of this study were as follows:
- At week 6 of YRC3780 supplementation, salivary cortisol levels at 2 hours and 6 hours after waking were significantly lower in the YRC3780 group compared to the placebo group (p=0.05).
- Salivary cortisol concentrations at 40 minutes after the TSST were significantly lower in the YRC3780 group (4.2 ± 4.4 nmol/L, mean ± SD) than in the placebo group (7.6 ± 4.7 nmol/L) (p=0.043).
- AIS scores at 6 weeks and GHQ-28 scores at 8 weeks were significantly lower in the YRC3780 group compared to the placebo group (AIS, p=0.031; GHQ-28, p=0.038) indicating better sleep quality and a better mental state.
Conclusion:
Oral supplementation with YRC3780 may have beneficial effects on the HPA axis response to acute psychological stress, potentially associated with a decrease in morning cortisol levels. Additionally, the study suggests that the lower basal activity and stress reactivity of the HPA axis may lead to improvements in subjective sleep quality and mental health.
Clinical practice applications:
- The precise mechanisms underlying the correlation between the gut microbiota and the gut-brain axis remain incompletely understood, emphasising the need for further research.
- This clinical trial demonstrated that daily intake of YRC3780 decreased morning salivary cortisol levels at 6 and 8 weeks and reduced the salivary cortisol response to acute psychological stress.
Considerations for future research:
- Larger, adequately powered clinical trials are required to provide deeper insights into the mechanisms responsible for the stress-reducing and sleep-improving effects of Lactococcus lactis subsp. cremoris.
- Furthermore, investigations into optimal dosage and duration of probiotic supplementation are warranted for a more comprehensive understanding, particularly in diverse demographic groups.
- Comparative research is needed to explore the effects of various probiotic strains on objective stress responses.
Abstract
BACKGROUND Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. METHODS Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. RESULTS The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. CONCLUSIONS Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.
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Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin.
Oda, K, Nomura, T, Nakane, T, Yamashita, K, Inoue, K, Ito, S, Vierock, J, Hirata, K, Maturana, AD, Katayama, K, et al
eLife. 2021
Abstract
Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore.
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Basic concepts and unique features of human circadian rhythms: implications for human health.
Yamanaka, Y
Nutrition reviews. 2020;(12 Suppl 2):91-96
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Abstract
Most physiological functions and behaviors exhibit a robust approximately 24-hour rhythmicity (circadian rhythm) in the real world. These rhythms persist under constant conditions, but the period is slightly longer than 24 hours, suggesting that circadian rhythms are endogenously driven by an internal, self-sustained oscillator. In mammals, including humans, the central circadian pacemaker is located in the hypothalamic suprachiasmatic nucleus. The primary zeitgeber for this pacemaker is bright sunlight, but nonphotic time cues also affect circadian rhythms. The human circadian system uniquely exhibits spontaneous internal desynchronization between the sleep-wake cycle and core body temperature rhythm under constant conditions and partial entrainment of the sleep-wake cycle in response to nonphotic time cues. Experimental and clinical studies of human circadian rhythms must take into account these unique features. This review covers the basic concepts and unique features of the human circadian system, the mechanisms underlying phase adjustment of the circadian rhythms by light and nonphotic time cues (eg, physical exercise), and the effects of eating behavior (eg, chewing frequency) on the circadian rhythm of glucose metabolism.
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Malnutrition at Admission Predicts In-Hospital Falls in Hospitalized Older Adults.
Ishida, Y, Maeda, K, Nonogaki, T, Shimizu, A, Yamanaka, Y, Matsuyama, R, Kato, R, Mori, N
Nutrients. 2020;(2)
Abstract
Malnutrition leads to poor prognoses, including a predisposition to falls. Few studies have investigated the relationship between malnutrition and falls during hospitalization. This study aimed to determine malnutrition's association with falls during hospitalization. A retrospective observational study was conducted. Patients aged ≥65 years that were admitted to and discharged from a university hospital between April 2018 and March 2019 were examined. Patients with independent basic activities of daily living were included. Diagnosis of malnutrition was based on the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria at admission. Disease information such as the Charlson Comorbidity Index (CCI) and reasons for hospitalization were reviewed. Kaplan-Meier curve and multivariate Cox regression analyses were performed. Data from 6081 patients (mean age: 74.4 ± 6.1 years; males: 58.1%) were analyzed. The mean CCI was 2.3 ± 2.8 points. Malnutrition was detected in 668 (11.0%) and falls occurred in 55 (0.9%) patients. Malnourished patients experienced a higher fall rate than those without malnutrition (2.4% vs. 0.7%, log-rank test p < 0.001). In multivariate analysis, malnutrition had the highest hazard ratio for falls among covariates (hazard ratio 2.78, 95% confidence interval 1.51-5.00, p = 0.001). In conclusion, malnutrition at the time of admission to hospital predicts in-hospital falls.
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Morning Mastication Enhances Postprandial Glucose Metabolism in Healthy Young Subjects.
Sato, A, Ohtsuka, Y, Yamanaka, Y
The Tohoku journal of experimental medicine. 2019;(3):193-201
Abstract
Postprandial glucose concentration is dependent on the time of day and its concentration in the morning is lower than in the evening. However, whether it is dependent on mastication at different times of the day has not been studied before. We hypothesized that mastication affects insulin-mediated glucose metabolism differently in the morning and evening in healthy individuals. Firstly, nine healthy male volunteers (22.0 ± 0.7 SEM years, body mass index 22.0 ± 1.0 kg/m2) performed a 75-g oral glucose tolerance test (OGTT). One week after the OGTT, they participated in a high-carbohydrate food (rice) consumption test with 10 or 40 chews per mouthful. Each experiment was conducted in the morning (0800 h) and evening (2000 h) on the same day. Blood samples were collected before and at 30-min intervals for 120 min after glucose or rice consumption. The incremental area under the curve (iAUC) for glucose in the OGTT was significantly lower in the morning than in the evening, whereas the iAUC for insulin was similar at both times. In participants who chewed 40 times, the iAUC for glucose after rice consumption was significantly lower in the morning than in the evening but was similar at both times in individuals who chewed 10 times. Chewing 40 times in the morning (but not the evening) significantly increased insulin secretion at 30 min. This suggests that morning mastication improves early-phase insulin secretion after rice consumption. This novel finding may aid in reducing the incidence of obesity and type 2 diabetes mellitus.
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Pharmacokinetics, safety, and efficacy of FOLFIRI plus bevacizumab in Japanese colorectal cancer patients with UGT1A1 gene polymorphisms.
Suenaga, M, Fuse, N, Yamaguchi, T, Yamanaka, Y, Motomura, S, Matsumoto, H, Hamamoto, Y, Mizunuma, N, Doi, T, Hatake, K, et al
Journal of clinical pharmacology. 2014;(5):495-502
Abstract
Previous reports of the influence of UGT1A1 gene polymorphisms on the pharmacokinetics of irinotecan metabolism have not assessed Asian patients treated with FOLFIRI plus bevacizumab for advanced and recurrent colorectal cancer. Twenty-one Japanese colorectal cancer patients received intravenous FOLFIRI (bolus irinotecan, folinic acid, and fluorouracil followed by 46-hour fluorouracil infusion) followed by bevacizumab (5 mg/kg) in Cycle 1. In Cycle 2, patients received bevacizumab followed by FOLFIRI. The regimen was in 2-week cycles. The area under-the-curves ratio (AUC0-last) (Cycle 2/Cycle 1) was determined from plasma concentrations of irinotecan and metabolites (SN-38, SN-38G). Safety, efficacy, and drug-drug interactions were analyzed. Median observation period was 7.8 months; median number of cycles 15. Drug-drug interactions were evaluated in eight patients without irinotecan dose reduction. Mean AUC0-last ratios (with/without bevacizumab) of irinotecan, SN-38, and SN-38G were 0.959, 0.927, and 0.931 respectively. Response rate was 65%; median progression-free survival 16.4 months. Response occurred in four patients with, and nine without, UGT1A1 polymorphism. No significant differences occurred between efficacy, safety, or polymorphism status. This cohort showed no differences in safety or efficacy compared to previous reports. Bevacizumab did not affect the pharmacokinetics of irinotecan and its metabolites, irrespective of UGT1A1 polymorphism status.
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Improvement in endothelial function by lifestyle modification focused on exercise training is associated with insulin resistance in obese patients.
Kurose, S, Tsutsumi, H, Yamanaka, Y, Shinno, H, Miyauchi, T, Tamanoi, A, Imai, M, Masuda, I, Kimura, Y
Obesity research & clinical practice. 2014;(1):e106-114
Abstract
A new method to evaluate endothelial function, namely, reactive hyperemia peripheral arterial tonometry (RH-PAT), has been developed. RH-PAT is an index of endothelial function, indicating initial atherosclerotic lesions. The present study aimed to investigate the effect of lifestyle modification with a focus on exercise training on RH-PAT in obese patients. We studied 43 obese patients (body mass index ≥ 30). RH-PAT was measured, and the RH-PAT index was calculated as a ratio of the digital pulse volume during reactive hyperemia divided by that at baseline. Further, we assessed body composition, arterial stiffness, insulin resistance, adipocytokine levels, and exercise tolerance. The exercise program consisted of 30 min on a cycle ergometer or treadmill, 3 times per week for 6 months. Training intensity was adjusted to the anaerobic threshold. Significant improvements were observed in the RH-PAT index following exercise training. We noted a significant reduction in weight, body fat percentage, and leptin values, and a significant increase in adiponectin levels and exercise tolerance. An abnormal baseline RH-PAT index was observed in 24 patients (55.8%); however, the improvement rate was higher in these patients than in patients with normal RH-PAT index values. Stepwise multiple regression analysis revealed that changes in insulin resistance (ΔHOMA-IR) were independently correlated with changes in the RH-PAT index. Our results indicate that lifestyle modification with a focus on exercise training improved the RH-PAT index in obese patients. Patients with abnormal RH-PAT index values before lifestyle modification with exercise training demonstrated a high rate of improvement following exercise. Further, our results suggest that insulin resistance was the only independent factor influencing improvement in endothelial function.
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[Modified FOLFOX6(mFOLFOX6)in metastatic colorectal carcinoma patients with poor performance status].
Nishi, T, Hamamoto, Y, Uemoto, J, Onodera, K, Warita, E, Yamanaka, Y
Gan to kagaku ryoho. Cancer & chemotherapy. 2012;(13):2557-60
Abstract
Because mFOLFOX6 has few contraindications, it is useful for poor performance status(PS)cases. However, in Japan, there are some reports that the dose is reduced easily. We retrospectively examined the safety/usefulness of the full dose mFOLFOX6(first-line)for advanced colon cancer patients with poor PS. Four of five cases had improved PS. The response rate was 60%. Grade 3/4 adverse events were infection, leukopenia, and neutropenia. Treatment-related deaths within 60 days of starting treatment were absent. Full-dose mFOLFOX6 for poor PS may be beneficial. However, we must consider the increased risk of adverse events.
