Background and Objectives Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups. Methods A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 different studies in different patient populations. Steady-state exposure was simulated and compared across patient subgroups for two US Food and Drug Administration/European Medicines Agency-approved drug labels and optimised doses were derived. Results The final model uses postmenstrual age, weight and serum creatinine as covariates. A 35-year-old, 70-kg patient with a serum creatinine level of 0.83 mg dL −1 (73.4 µmol L −1) has a V 1 , V 2 , CL and Q 2 of 42.9 L, 41.7 L, 4.10 L h −1 and 3.22 L h −1. Clearance matures with age, reaching 50% of the maximal value (5.31 L h −1 70 kg −1) at 46.4 weeks postmenstrual age then declines with age to 50% at 61.6 years. Current dosing guidelines failed to achieve satisfactory steady-state exposure across patient subgroups. After optimisation, increased doses for the Food and Drug Administration label achieve consistent target attainment with minimal (± 20%) risk of under-and over-dosing across patient subgroups. Conclusions A population model was developed that is useful for further development of age and kidney function-stratified dosing regimens of vancomycin and for individualisation of treatment through therapeutic drug monitoring and Bayesian forecasting.

This study examined acute hormone and recovery responses to resistance exercise with slow movements. Six men performed three types of exercise regimens (five sets of knee extension exercise): (1) high-intensity resistance exercise with normal movement (HN; 1 s for lifting action, 1 s for lowering action), (2) low-intensity resistance exercise with slow movement (LS; 3 s for lifting action, 3 s for lowering action), and (3) low-intensity resistance exercise with normal movement (LN; 1 s for lifting action, 1 s for lowering action). The intensity in the first set was set at approximately 80% of 1RM for HN and 40% of 1RM for LS and LN. In the HN and LS, the subjects performed each exercise set until exhaustion. In the LN, both intensity and number of repetitions were matched with those for LS. The total work volume in the HN showed approximately double the value of LS and LN (P < 0.05). Electromyography (EMG) data indicated that LS showed sustained EMG signals throughout the exercise. During the exercise, the HN and LS showed lower muscle oxygenation levels. After the exercise, LS caused significantly greater norepinephrine and free testosterone responses (delta value) than in the HN and LN (P < 0.05). However, no significant difference was observed in the recovery of maximal isometric strength, isokinetic strength, and jump performance between the HN and LS. These results indicate that slow movements during the resistance exercise are important for the enhancement of hormonal responses, especially catecholamine and free testosterone, but they do not affect muscle strength recovery. [5,6]. Although muscle growth can occur in the absence of elevations of circulating anabolic hormones [7], muscular hypertrophy and strength gain after prolonged training might be related, at least in part, to exercise-induced increases in anabolic hormones [1].In general, a training intensity of greater than 65% of one repetition maximum (1RM) is considered the minimum intensity to induce muscular hypertrophy and strength gain [8]. However, resistance exercise at high intensity would not be appropriate for some individuals, including sedentary, frail, and elderly people. Therefore it is necessary to develop effective regimens with reduced mechanical loads. Evidence from several studies indicates that low-intensity (20%-50% 1RM) exercise with moderate vascular occlusion markedly increases acute GH secretion [9-11] and considerable muscular hypertrophy [12]. However, resistance exercises with vascular occlusion require special equipment and careful monitoring of blood flow and occlusive pressure. Alternatively, a lowintensity resistance exercise (~50% 1RM) with slow lift and tonic force generation has been shown to enhance GH secretion [13], and muscular hypertrophy, and strength gains [14]. Moreover, a low-intensity (~50% 1RM) exercise with combined slow movements and a short interset rest has been reported to increase muscular size and strength in middle-aged women [15]. The mechanisms of slow-movement exercise for inducing ...

AimsCancer is a leading cause of morbidity and mortality worldwide; therefore, effective measures for cancer prevention and treatment are in constant demand. The extracts of Inonotus obliquus (Chaga mushroom) demonstrate potent anti-tumor activities and have been used to treat cancer in several countries; however, the actual effect and underlying mechanisms are still unclear. In the present study, we aimed to investigate the effects of continuous intake of aqueous extract from I. obliquus on tumor suppression.Main methodsAnticancer activity of the I. obliquus extract was examined in mouse models of Lewis lung carcinoma growth and spontaneous metastasis after 3 weeks of continuous extract intake at the dose of 6 mg/kg/day, which corresponded to that ingested daily with Chaga infusion in Japan.Key findingsThe extract of I. obliquus caused significant tumor suppressive effects in both models. Thus, in tumor-bearing mice, 60% tumor reduction was observed, while in metastatic mice, the number of nodules decreased by 25% compared to the control group. Moreover, I. obliquus extract-treated mice demonstrated the increase in tumor agglomeration and inhibition of vascularization. Interestingly, I. obliquus intake decreased body weight in middle-aged mice and increased body temperature in response to light-dark switching in mature adult mice. Furthermore, I. obliquus prevented temperature drop in mice after tumor implantation.SignificanceOur findings suggest that the I. obliquus extract could be used as a natural remedy for cancer suppression by promoting energy metabolism.

Ultrasound guidance for puncturing and tip positioning is a promising option for the placement of peripherally inserted central catheters. Ultrasound guidance could dispense with radiation exposure and the transfer of patients to the X-ray department.

Recently, transradial angiography and intervention have been performed with high success rates and low rates of vascular complications. The incidence of compartment syndrome after the transradial approach seems to be very low. However, bleeding in the arm can occur and may lead to the devastating complication of compartment syndrome of the forearm, which if not treated early, can evolve into a disability of the arm. In fact, most cases of such complications are caused by guidewire- or catheter-induced damage to small arterial branches that are considerably proximal to the puncture site. However, we encountered a case of compartment syndrome that was not caused by bleeding or hematoma formation and required urgent fasciotomy for its treatment. The forearm wounds were left open to allow the edema to resolve and closed after 1 week. The patient recovered and was discharged, with full movement of his forearm and hand. We suspect that an arterial spasm induced by the radial sheath or catheter resulted in ischemia of the forearm muscles. To our knowledge, this is the first reported case in which acute compartment syndrome of the forearm occurred after transradial intervention and was not due to bleeding or hematoma formation.