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We investigated the influence of the menstrual cycle (MC) on leukocyte response after exercise-induced muscle damage (EIMD). During the early follicular (E-FP, n = 12) or mid-luteal phase (M-LP, n = 12), 24 untrained females with eumenorrhea performed 60 eccentric exercises using nondominant arms. Blood samples were collected at pre- and 4, 48, and 96 h postexercise to analyze estradiol and progesterone concentrations, leukocyte count and fractionation, and creatine kinase (CK) activity. We also assessed the maximal voluntary isometric contraction torque of elbow flexion, range of motion in the elbow joint, upper-arm circumference, and muscle soreness as indirect muscle damage markers at pre-; immediately post-; and 4, 48, and 96 h postexercise. The percent change in neutrophil counts from pre- to 4 h postexercise was lower in M-LP than in E-FP (E-FP, 30.7% [15.9–65.7%] vs. M-LP, 10.3% [−2.3–30.0%]; median [interquartile range: 25–75%]; p = 0.068). Progesterone concentration at pre-exercise was significantly negatively correlated with the percent change in neutrophil counts from pre- to 4 h postexercise in M-LP (r = −0.650, p = 0.022). MC did not affect CK activity or other muscle damage markers. Thus, progesterone concentration rather than MC may be related to neutrophil response following EIMD.

Endothelin-1 (ET-1), produced by vascular endothelial cells, plays a pivotal role in the regulation of vascular tone. Isomaltulose, a naturally occurring sweetener and structural isomer of sucrose, reduces postprandial hyperglycemia, but its effect on arteriosclerosis due to hyperglycemia is unknown. The effects of 12 weeks of isomaltulose administration on ET-1 levels, a peptide that regulates arterial stiffness, blood pressure, and vascular tone, were tested before and after an oral glucose tolerance test. Fifty-four healthy middle-aged and older adults (30 men and 24 women) were divided into two groups: (1) a 25 g isomaltulose jelly drink intake group (Group I, 27 participants, mean age 55 ± 1 years) and (2) a sucrose jelly drink intake group (Group S, 27 participants, mean age 55 ± 1 years), each consuming isomaltulose or sucrose daily for 12 weeks, and a randomized, controlled study was conducted. Participants visited the laboratory before the intervention and 4, 8, and 12 weeks after the intervention to measure carotid–femoral (cf) and brachial–ankle (ba) pulse wave velocity (PWV), systolic blood pressure (BP), plasma glucose (PG), insulin, and ET-1 levels before and 60 and 120 min after a 75-g OGTT. baPWV, and ET-1 levels before intervention were significantly increased after 75-g OGTT compared to before 75-g OGTT in both groups ( p  < 0.05). The post-intervention baPWV, and ET-1 levels were significantly increased after 75-g OGTT in Group S compared to before 75-g OGTT ( p  < 0.05), whereas no significant changes were observed in Group I. These results suggest that consumption of isomaltulose, which has a lower GI than sucrose, is more effective in preventing the increases in systemic arterial stiffness associated with postprandial hyperglycemia in healthy middle-aged and older adults.

In women, fat oxidation during exercise changes with the menstrual cycle. This study aimed to investigate the effect of green tea extract (GTE) ingestion on fat oxidation during exercise depending on the menstrual cycle phase. Ten women with regular menstrual cycles participated in this randomized, double-blind, crossover study. GTE or placebo was administered during the menstrual cycle’s follicular phase (FP) and luteal phase (LP). Participants cycled for 30 min at 50% maximal workload, and a respiratory gas analysis was performed. Serum estradiol, progesterone, free fatty acid, plasma noradrenaline, blood glucose, and lactate concentrations were assessed before, during, and after the exercise. Fat oxidation, carbohydrate oxidation, and the respiratory exchange ratio (RER) were calculated using respiratory gas. Fat oxidation during the exercise was significantly higher in the FP than in the LP with the placebo (p < 0.05) but did not differ between the phases with GTE. Carbohydrate oxidation, serum-free fatty acid, plasma noradrenaline, blood glucose, and lactate concentrations were not significantly different between the phases in either trial. Our results suggest that GTE ingestion improves the decrease in fat oxidation in the LP.

This study aimed to assess the effects of co-ingestion of carbohydrate with milk (MILK) and isocaloric carbohydrate beverage (CHO) on post-exercise recovery and subsequent exercise capacity, considering the menstrual cycle. This study included 12 women with regular menstrual cycles who completed four test days, which started with glycogen-depleting exercise using a cycle ergometer in the early follicular phase (EF) and late follicular phase (LF), followed by 240 min of recovery from the ingestion of 200 mL of CHO or MILK every 30 min immediately after the exercise (POST0) until 210 min post-exercise. After 240 min, participants performed an exercise capacity test. Blood samples and breathing gas samples were collected before the exercise (PRE), POST0, and 120 (POST120) and 240 min after the end of exercise (POST240) to determine the concentrations of estradiol, progesterone, blood glucose, blood lactate, free fatty acid (FFA), and insulin and the respiratory exchange ratio, fat oxidation, and carbohydrate oxidation. The exercise time at exercise capacity test was not significantly different in terms of menstrual cycle phases and recovery beverages ingested. However, there was a significant positive correlation between the exercise capacity test and area under the curve (AUC) of FFA concentrations from POST0 to POST240 in each group (EF + CHO, p < 0.05; LF + CHO, p < 0.05; EF + MILK, p < 0.01; and LF + MILK, p < 0.05). The AUC of FFA from POST120 to POST240 showed no difference between EF (CHO and MILK) and LF (CHO and MILK). However, the AUC of FFA concentrations from POST120 to POST240 was significantly greater in MILK (EF and LF) than that in CHO (EF and LF) (p < 0.05). In active women, circulating substrates and hormone concentrations during short recovery post-exercise are not affected by the menstrual cycle. However, MILK may affect circulating substrates during recovery and the exercise capacity after recovery.

This study aimed to assess the effects of co-ingestion of carbohydrate with milk (MILK) and isocaloric carbohydrate beverage (CHO) on post-exercise recovery and subsequent exercise capacity, considering the menstrual cycle. This study included 12 women with regular menstrual cycles who completed four test days, which started with glycogen-depleting exercise using a cycle ergometer in the early follicular phase (EF) and late follicular phase (LF), followed by 240 min of recovery from the ingestion of 200 mL of CHO or MILK every 30 min immediately after the exercise (POST0) until 210 min post-exercise. After 240 min, participants performed an exercise capacity test. Blood samples and breathing gas samples were collected before the exercise (PRE), POST0, and 120 (POST120) and 240 min after the end of exercise (POST240) to determine the concentrations of estradiol, progesterone, blood glucose, blood lactate, free fatty acid (FFA), and insulin and the respiratory exchange ratio, fat oxidation, and carbohydrate oxidation. The exercise time at exercise capacity test was not significantly different in terms of menstrual cycle phases and recovery beverages ingested. However, there was a significant positive correlation between the exercise capacity test and area under the curve (AUC) of FFA concentrations from POST0 to POST240 in each group (EF + CHO, p < 0.05; LF + CHO, p < 0.05; EF + MILK, p < 0.01; and LF + MILK, p < 0.05). The AUC of FFA from POST120 to POST240 showed no difference between EF (CHO and MILK) and LF (CHO and MILK). However, the AUC of FFA concentrations from POST120 to POST240 was significantly greater in MILK (EF and LF) than that in CHO (EF and LF) (p < 0.05). In active women, circulating substrates and hormone concentrations during short recovery post-exercise are not affected by the menstrual cycle. However, MILK may affect circulating substrates during recovery and the exercise capacity after recovery.

The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014–2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan. Here, Kodama et al. describe the discovery, isolation and characterization of a novel tick-borne orthonairovirus, designated Yezo virus (YEZV), from patients with an acute febrile illness in Japan. Serological testing of wildlife and molecular screening of ticks suggest an endemic circulation of YEZV in Japan.

PurposeIn drug discovery, rats are widely used for pharmacological and toxicological studies. We previously reported that a mechanism-based oral absorption model, the gastrointestinal unified theoretical framework (GUT framework), can appropriately predict the fraction of a dose absorbed (Fa) in humans and dogs. However, there are large species differences between humans and rats. The purpose of the present study was to evaluate the predictability of the GUT framework for rat Fa.MethodThe Fa values of 20 model drugs (a total of 39 Fa data) were predicted in a bottom-up manner. Based on the literature survey, the bile acid concentration (Cbile) and the intestinal fluid volume were set to 15 mM and 4 mL/kg, respectively, five and two times higher than in humans. LogP, pKa, molecular weight, intrinsic solubility, bile micelle partition coefficients, and Caco-2 permeability were used as input data.ResultsThe Fa values were appropriately predicted for highly soluble drugs (absolute average fold error (AAFE) = 1.65, 18 Fa data) and poorly soluble drugs (AAFE = 1.57, 21 Fa data). When the species difference in Cbile was ignored, Fa was over- and under-predicted for permeability and solubility limited cases, respectively. High Cbile in rats reduces the free fraction of drug molecules available for epithelial membrane permeation while increasing the solubility of poorly soluble drugs.ConclusionThe Fa values in rats were appropriately predicted by the GUT framework. This result would be of great help for a better understanding of species differences and model-informed preclinical formulation development.

Cancer immunotherapy, including immune checkpoint inhibitors, exerts beneficial effects in cancer patients. However, immune checkpoint inhibitors are only advantageous for a limited population of cancer patients. Therefore, companion diagnostics are needed in order to identify patients for whom these therapies are effective. In the present study, we evaluated detailed immunological aspects in clinical specimens from non-small cell lung cancer (NSCLC) patients. We analyzed the immune profiles, T cell cytotoxicity, and TCR repertoire of peripheral blood, normal lung tissue, and tumor tissue from NSCLC patients. By using bispecific T-cell engager technology to assess the cytotoxicity of T cells, we found that the cytotoxicity of tumor-infiltrated T cells closely correlated with that of peripheral T cells. This correlation was supported by the immune profiles, cytokine production, and results of the TCR repertoire analysis from these specimens. We also found that the cytotoxicity of peripheral T cells has potential as a predictor of the effects of nivolumab in the tumor microenvironment. These results imply further applications to blood-based immune monitoring systems and predictive biomarkers for cancer immunotherapy.

Background and objectives: The aim of this study was to determine the associations of dietary diversity with prevalences of allergic diseases. Methods and study design: The participants were 1,317 men and women aged 20 to 63 years who were living in tokushima prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics and current medical histories of allergic diseases using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the quantitative index for dietary diversity (quantidd). The ors and 95% cis for each of the allergic diseases with a 1 standard deviation (sd) increase in the quantidd score were estimated, controlling for age, family history of allergic diseases, education, smoking, drinking, physical activity, energy intake and bmi. Results: Higher dietary diversity showed significant inverse dose-response relationships with allergic diseases and allergic rhinitis in women. Multivariate-adjusted ors (95% ci) for allergic diseases and allergic rhinitis with 1 sd increase in the quantidd score were 0.77 (95% ci: 0.60-0.98, 'p'=0.037) and 0.69 (95% ci: 0.53-0.90, 'p'=0.007), respectively, in women. There were no significant associations between dietary diversity and allergic diseases in men. Conclusions: The results indicate that there is an inverse association between higher dietary diversity and allergic rhinitis in Japanese female workers.