Effects of concomitant use of prasugrel with edoxaban on bleeding time, pharmacodynamics, and pharmacokinetics of edoxaban in healthy elderly Japanese male subjects: a clinical pharmacology study.

BACKGROUND: Dual therapy with a direct oral anticoagulant (DOAC) plus a P2Y12 receptor inhibitor is recommended in patients with nonvalvular atrial fibrillation who undergo percutaneous coronary intervention. Thus, we evaluated the effects of DOAC edoxaban plus P2Y12 receptor inhibitor prasugrel on bleeding time (BT), and pharmacodynamics (PD) and pharmacokinetics (PK) of edoxaban in healthy elderly Japanese male subjects. METHODS: A single-center, clinical pharmacology study with randomized, open-label, repeated dosing enrolled 24 participants in two groups of 12 receiving 30 mg edoxaban once daily for 3 days; then 30 mg edoxaban plus 2.5 mg prasugrel (Group 1) or 30 mg edoxaban plus 3.75 mg prasugrel (Group 2) once daily for 5 days. Primary endpoint was BT by the Ivy method. Secondary endpoints were the PD parameters of prothrombin time (PT), activated partial thromboplastin time (aPTT), prothrombin fragment F1 + 2 (F1 + 2), and P2Y12 reaction units (PRU), and PK profiles of edoxaban alone and in combination with prasugrel. RESULTS: Geometric least squares mean of BT ratios (vs. baseline) for 3-day edoxaban treatment were 1.097 (90% confidence interval (CI) 0.911-1.321) in Group 1 and 1.327 (90% CI 1.035-1.703) in Group 2; for 5-day edoxaban plus 2.5 mg and 3.75 mg prasugrel, they were 1.581 (90% CI 1.197-2.087) and 1.996 (90% CI 1.482-2.690), respectively. Contributions of prasugrel to the effects (edoxaban + prasugrel/edoxaban) were 1.442 (90% CI 1.096-1.897) in Group 1 and 1.504 (90% CI 1.172-1.930) in Group 2. Edoxaban prolonged PT and aPTT and decreased F1 + 2. Adding on prasugrel did not appreciably change PT, aPTT, or F1 + 2. Prasugrel reduced PRU, whereas edoxaban had no effect on PRU. We recorded 26 adverse events; 23 were treatment-emergent (positive fecal occult blood test). All participants with adverse events recovered during follow-up. CONCLUSIONS: Coadministration of 2.5 mg and 3.75 mg prasugrel with 30 mg edoxaban prolonged BT in healthy elderly Japanese male subjects. The effect was dependent on the dose of prasugrel. Prasugrel did not affect PD or PK profiles of edoxaban. Edoxaban had no effect on PD of prasugrel. TRIAL REGISTRATION: Japan Registry of Clinical Trials No. jRCTs071190006; registration date, 26-April-2019.

Short-Term, Combined Fasting and Exercise Improves Body Composition in Healthy Males.

Fasting enhances the beneficial metabolic outcomes of exercise; however, it is unknown whether body composition is favorably modified on the short term. A baseline-follow-up study was carried out to assess the effect of an established protocol involving short-term combined exercise with fasting on body composition. One hundred seven recreationally exercising males underwent a 10-day intervention across 15 fitness centers in the Netherlands involving a 3-day gradual decrease of food intake, a 3-day period with extremely low caloric intake, and a gradual 4-day increase to initial caloric intake, with daily 30-min submaximal cycling. Using dual-energy X-ray absorptiometry analysis, all subjects substantially lost total body mass (-3.9 ± 1.9 kg; p < .001) and fat mass (-3.3 ± 1.3 kg; p < .001). Average lean mass was lost (-0.6 ± 1.5 kg; p < .001), but lean mass as a percentage of total body mass was not reduced. The authors observed a loss of -3.9 ± 1.9% android fat over total fat mass (p < .001), a loss of -2.2 ± 1.9% gynoid over total fat mass (p < .001), and reduced android/gynoid ratios (-0.05 ± 0.1; p < .001). Analyzing 15 preselected single-nucleotide polymorphisms in 13 metabolism-related genes revealed trending associations for thyroid state-related single-nucleotide polymorphisms rs225014 (deiodinase 2) and rs35767 (insulin-like growth factor1), and rs1053049 (PPARD). In conclusion, a short period of combined fasting and exercise leads to a substantial loss of body and fat mass without a loss of lean mass as a percentage of total mass.

Influence of oral nutritional agents rich in soluble dietary fiber on intestinal flora of elderly men with malnutrition.

OBJECTIVE: Observe the influence of oral nutritional agents rich in soluble dietary (enteral nutritional suspension [TPF-DM]) on intestinal flora of elderly male subjects with malnutrition. METHOD: Seventy-eight subjects with good nutrition were considered as the healthy control group. Twenty-eight male subjects who had malnutrition and were older than 70 years were included and randomly divided into the short-term (3 months) intervention group (n = 20) and the long-term (12 months) group (n = 8). They were provided with enteral nutritional suspension (TPF-DM) 500 mL/day or maximum tolerance dose, so as to observe the changes in nutrition-related indexes and intestinal flora after the elderly take enteral nutritional suspension (TPF-DM). RESULTS: (1) For elderly male subjects with malnutrition, their body weight, body mass index, hemoglobin, total protein, and albumin were significantly lower than the control group with favorable nutrition. (2) There were obvious differences in intestinal flora between healthy elderly male subjects and those with malnutrition. After the treatment of enteral nutritional suspension (TPF-DM), intestinal flora of the malnourished elderly subjects showed recovery toward the healthy elderly subjects. The obvious gradient changes of the flora were mainly in the bacteroidetes, firmicutes, and proteobacteria phyla, and the relative abundance of CAG2 clusters in the malnourished group was higher than that in the healthy control group, and the relative abundance decreased after long-term treatment, and the change approached the healthy control group. The relative abundance of CAG3 and CAG6 clusters in the malnourished group was lower than that in the healthy control group, and the relative abundance increased after long-term treatment, and the change approached the healthy control group. CONCLUSION: Malnutrition has obvious impact on intestinal flora of the elderly. Enteral nutritional suspension (TPF-DM) not only prevents the further decline in the state of nutrition but also helps the recovery in intestinal flora of the elderly. Long-term application can produce better effects.

Do nutritional behaviors depend on biological sex and cultural gender?

Conventional knowledge, resulting from observations and experience, maintains the conviction that there are gender differences in the acquisition, preparation and consumption of food. This review shows differences between the sexes in eating behavior, food choice and nutritional strategy which were conditioned by evolution and by intra-individual (biological or psychological) and extra-individual (socioeconomic and cultural) factors. Women manifest a more pronounced trust in healthy nutrition, greater engagement in controlling body weight, a higher tendency to eat in a group and in stressful situations, and they frequently experience frustration due to their own nutritional behaviors, which reflects higher social pressure and their attempts to reduce eating-related pleasure. On the other hand, men prefer fatty meals with a strong taste, and are directed mainly by the pleasure of consumption; they more frequently furtively eat sweet foods while watching television, use more dietary supplements and more frequently visit fast food restaurants. Nutritional behavior, styles of nutrition, dietary profiles, approach to nourishment, approach to the place of meal consumption, and the sources of nutritional knowledge all demonstrate associations with gender. Reciprocal interactions between gender and diet are conditioned by physiological, psychological and sociocultural factors. This system of reciprocal interactions includes feedback: biological sex and cultural gender shape one's diet and, reciprocally, one's diet affects the deepening or flattening of gender differences. The analysis of reciprocally interacting factors entangled in the formation of a nutritional model may also represent an important element of pro-health prophylaxis and should be used in medical and dietary practice. Males in particular should be informed and educated about health-promoting diets.

Levocetirizine Oral Disintegrating Tablet: A Randomized Open-Label Crossover Bioequivalence Study in Healthy Japanese Volunteers.

Levocetirizine is classified as a second-generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate-release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study.

Variation of Tpeak-end, corrected Tpeak-end, QT, and corrected QT intervals, Tpeak-end/QT, Tpeak-end/corrected QT ratios and heart rate variability according to decades in the healthy male subjects aged between 30 and 79 years.

BACKGROUND: Heart rate variability (HRV) is a predictor of cardiac autonomic functions. Ventricular repolarization markers can indicate ventricular arrhythmias. We aimed to evaluate variations of HRV and these repolarization markers in five healthy male groups between age 30 and 79 years according to decades. MATERIALS AND METHODS: The study group consisted of 500 healthy male subjects between October 2018 and May 2019. The male subjects were divided into five categories according to their ages. Then, electrocardiograms (ECG), transthoracic echocardiograms (TTE), and treadmill exercise test (TET) were performed. T-wave peak-end (Tp-e) interval was defined as the time between the peak point and end of T-wave. Tp-e, corrected Tp-e (cTp-e), QT, and corrected QT (QTc) were measured from the resting ECGs and HRV temporal parameters (SDNN, SDNN Index, SDANN Index, RMSSD, sNN50, and pNN50), and HRV frequency parameters (VLF, LF, HF, and LF/HF) were obtained from 24-hour Holter monitorization recordings. One-way ANOVA test was used for the differences between the groups. Pearson correlation test was used to determine the correlations between the values of all groups. RESULTS: Considering the repolarization parameters, there are significant differences in five groups in terms of Tp-e interval, but not Tp-e/QT and Tp-e/QTc ratios. Considering the HRV parameters, there were statistically significant differences between the five male healthy groups in terms of HRV temporal parameters and there are no significant differences in terms of HRV frequency parameters. CONCLUSION: As the age increases, basal Tp-e interval increases and HRV temporal parameters decrease significantly in the male subjects aged between 30 and 79 years, but HRV frequency parameters do not change.

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra-performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N-glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N-glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms.

Standard values of the upper body posture in male adults.

BACKGROUND: Interactions within the musculoskeletal system have been investigated and confirmed in numerous studies. OBJECTIVES: Since there are no standard values for the posture of healthy persons, this study attempts to define reference values for the upper body posture in healthy men. MATERIAL AND METHODS: A 3-dimensional back scan was performed to quantify the upper back posture while habitually standing. Tolerance regions for habitual posture were calculated, including the upper and lower limit for 95% of all values. Furthermore, the left and right limit of the confidence interval (CI) was carried out. Group differences were tested by using the t-test or the Wilcoxon-Mann-Whitney U test. RESULTS: Height, weight and body mass index (BMI) of the participants were comparable to those of the average young German males. The spinal column was marginally twisted to the right. The spinal curves, defined by the thoracic or lumbar flexion angle, and the kyphosis and lordosis angle, indicated that the angle in the thoracic spine area was larger than that in the lumbar region. Consequently, a more kyphotic posture was observed in the sagittal plane. The habitual posture was slightly scoliotic, with a rotational component (scapular depression left, right scapula marginally located more dorsally, high state of pelvic left, iliac left further rotated posteriorly and simultaneously tilted further ventrally). No significant difference between right and left-handed persons could be proven. CONCLUSIONS: Video raster stereography is a suitable method to measure the 3-dimensional back surface. Using this method for healthy young men, we observed that they had an almost ideally balanced posture with minimal ventral body inclination and a marginal scoliotic deviation. The normal values allow a better comparison of data between different studies of body posture.