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Next-generation sequencing of AML has identified specific genetic mutations in AML patients. Hematologic Malignancies (HM)-SCREEN-Japan 01 is a multicenter study to detect actionable mutations using paraffin-embedded bone marrow (BM) clot specimens rather than BM fluid in AML patients for whom standard treatment has not been established. The purpose of this study is to evaluate the presence of potentially therapeutic target gene mutations in patients with newly diagnosed unfit AML and relapsed/refractory AML (R/R-AML) using BM clot specimens. In this study, 188 patients were enrolled and targeted sequencing was undertaken on DNA from 437 genes and RNA from 265 genes. High-quality DNA and RNA were obtained using BM clot specimens, with genetic alterations successfully detected in 177 patients (97.3%), and fusion transcripts in 41 patients (23.2%). The median turnaround time was 13 days. In the detection of fusion genes, not only common fusion products such as RUNX1-RUX1T1 and KMT2A rearrangements, but also NUP98 rearrangements and rare fusion genes were observed. Among 177 patients (72 with unfit AML, 105 with R/R-AML), mutations in KIT and WT1 were independent factors for overall survival (hazard ratio = 12.6 and 8.88, respectively), and patients with high variant allele frequency (≥40%) of TP53 mutations had a poor prognosis. As for the detection of actionable mutations, 38% (n = 69) of patients had useful genetic mutation (FLT3-ITD/TKD, IDH1/2, and DNMT3A R822 ) for treatment selection. Comprehensive genomic profiling using paraffin-embedded BM clot specimens successfully identified leukemic-associated genes that can be used as therapeutic targets., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We previously reported that low-intensity [50% of one repetition maximum (1RM)] resistance training with slow movement and tonic force generation (LST) causes muscle hypertrophy and strength gain in older participants. The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity (30%1RM) increases muscle size and strength in older adults. Eighteen participants (60-77 years) were randomly assigned to two groups. One group performed very low-intensity (30% 1RM) knee extension exercise with continuous muscle contraction (LST: 3-s eccentric, 3-s concentric, and 1-s isometric actions with no rest between each repetition) twice a week for 12 weeks. The other group underwent intermitted muscle contraction (CON: 1-s concentric and 1-s eccentric actions with 1-s rest between each repetition) for the same time period. The 1RM, isometric and isokinetic strengths, and cross-sectional image of the mid-thigh obtained by magnetic resonance imaging were examined before and after the intervention. LST significantly increased the cross-sectional area of the quadriceps muscle (5.0%, P<0.001) and isometric and isokinetic knee extension strengths (P<0.05). CON failed to increase muscle size (1.1%, P = 0.12), but significantly improved its strength (P<0.05). These results indicate that even if the intensity is as low as 30% 1RM, LST can increase muscle size and strength in healthy older adults. The large total contraction time may be related to muscle hypertrophy and strength gain. LST would be useful for preventing sarcopenia in older individuals., (© 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

To compare the effects of a periodic resistance training (PTR) program with those of a continuous resistance training (CTR) program on muscle size and function, 14 young men were randomly divided into a CTR group and a PTR group. Both groups performed high-intensity bench press exercise training [75 % of one repetition maximum (1-RM); 3 sets of 10 reps] for 3 days per week. The CTR group trained continuously over a 24-week period, whereas the PTR group performed three cycles of 6-week training (or retraining), with 3-week detraining periods between training cycles. After an initial 6 weeks of training, increases in cross-sectional area (CSA) of the triceps brachii and pectoralis major muscles and maximum isometric voluntary contraction of the elbow extensors and 1-RM were similar between the two groups. In the CTR group, muscle CSA and strength gradually increased during the initial 6 weeks of training. However, the rate of increase in muscle CSA and 1-RM decreased gradually after that. In the PTR group, increase in muscle CSA and strength during the first 3-week detraining/6-week retraining cycle were similar to that in the CTR group during the corresponding period. However, increase in muscle CSA and strength during the second 3-week detraining/6-week retraining cycle were significantly higher in the PTR group than in the CTR group. Thus, overall improvements in muscle CSA and strength were similar between the groups. The results indicate that 3-week detraining/6-week retraining cycles result in muscle hypertrophy similar to that occurring with continuous resistance training after 24 weeks.

Single-joint resistance training with blood flow restriction (BFR) results in significant increases in arm or leg muscle size and single-joint strength. However, the effect of multijoint BFR training on both blood flow restricted limb and non-restricted trunk muscles remain poorly understood. To examine the impact of BFR bench press training on hypertrophic response to non-restricted (chest) and restricted (upper-arm) muscles and multi-joint strength, 10 young men were randomly divided into either BFR training (BFR-T) or non-BFR training (CON-T) groups. They performed 30% of one repetition maximal (1-RM) bench press exercise (four sets, total 75 reps) twice daily, 6 days week(-1) for 2 weeks. During the exercise session, subjects in the BFR-T group placed elastic cuffs proximally on both arms, with incremental increases in external compression starting at 100 mmHg and ending at 160 mmHg. Before and after the training, triceps brachii and pectoralis major muscle thickness (MTH), bench press 1-RM and serum anabolic hormones were measured. Two weeks of training led to a significant increase (P<0.05) in 1-RM bench press strength in BFR-T (6%) but not in CON-T (-2%). Triceps and pectoralis major MTH increased 8% and 16% (P<0.01), respectively, in BFR-T, but not in CON-T (-1% and 2%, respectively). There were no changes in baseline concentrations of anabolic hormones in either group. These results suggest that BFR bench press training leads to significant increases in muscle size for upper arm and chest muscles and 1-RM strength.

Three novel furoquinoline alkaloid oxogeranyl ethers (1-3) and one known furoquinoline alkaloid (4) were isolated from the leaves of Boninia glabra, an endemic plant of the Bonin Islands. Their structures were elucidated on the basis of spectroscopic analysis.

The Yamato-791198 and Murchison carbonaceous chondrites were analyzed for dipeptides and diketopiperazines as well as amino acids and hydantoins by gas chromatography combined with mass spectrometry. Glycylglycine (gly-gly) and cyclo(gly-gly) were detected at the concentrations of 11 and 18 pmol g-1, respectively, in Yamato-791198, and 4 and 23 pmol g-1, respectively, in Murchison. No other dipeptide and diketopiperazine were detected. Five hydantoins were detected at 8 to 65 pmol g-1 in Yamato-791198 and seven in Murchison at 6 to 104 pmol g-1. Total concentration of the glycine (gly) dimers is approximately four orders of magnitude less than the concentration of free gly in Yamato-791198, and three orders of magnitude less than that in Murchison. The absence of L- and LL-stereoisomers of dipeptides consisting of protein amino acids indicates that gly-gly and cyclo(gly-gly) detected are native to the chondries and not from terrestrial contaminants. A possibility was discussed that the gly dimers might have been formed by condensation of gly monomers but not formed through N-carboxyanhydrides of gly.