Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome-related myeloid disorders is poorly understood, except for GATA1 mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single GATA1 mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%), CTCF (20%), and EZH2, KANSL1 and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases, MPL, SH2B3 (LNK) and multiple RAS pathway genes (47%).

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BackgroundTo examine the effects of a multicomponent exercise program on the cognitive function of older adults with amnestic mild cognitive impairment (aMCI).MethodsDesign: Twelve months, randomized controlled trial; Setting: Community center in Japan; Participants: Fifty older adults (27 men) with aMCI ranging in age from 65 to 93 years (mean age, 75 years); Intervention: Subjects were randomized into either a multicomponent exercise (n = 25) or an education control group (n = 25). Subjects in the multicomponent exercise group exercised under the supervision of physiotherapists for 90 min/d, 2 d/wk, for a total of 80 times over 12 months. The exercises included aerobic exercises, muscle strength training, and postural balance retraining, and were conducted using multiple conditions to stimulate cognitive functions. Subjects in the control group attended three education classes regarding health during the 12-month period. Measurements were administered before, after the 6-month, and after the 12-month intervention period; Measurements: The performance measures included the mini-mental state examination, logical memory subtest of the Wechsler memory scale-revised, digit symbol coding test, letter and categorical verbal fluency test, and the Stroop color word test.ResultsThe mean adherence to the exercise program was 79.2%. Improvements of cognitive function following multicomponent exercise were superior at treatment end (group × time interactions for the mini-mental state examination (P = 0.04), logical memory of immediate recall (P = 0.03), and letter verbal fluency test (P = 0.02)). The logical memory of delayed recall, digit symbol coding, and Stroop color word test showed main effects of time, although there were no group × time interactions.ConclusionsThis study indicates that exercise improves or supports, at least partly, cognitive performance in older adults with aMCI.

We found that the NCGG-FAT using a tablet PC was reliable in a sample of community-dwelling older adults. The NCGG-FAT might be useful for cognitive screening in population-based samples and outcomes, enabling assessment of the effects of intervention on multidimensional cognitive function among older adults.

Seasonal changes in ambient temperature and day length are thought to modify habitual physical activity. However, relationships between such environmental factors and the daily physical activity of older populations remain unclear. The present study thus examined associations between meteorological variables and the number of steps taken per day by elderly Japanese. Continuous pedometer counts over a 450-day period were collected from 41 healthy subjects (age 71+/-4 years), none of whom engaged in any specific occupational activity or exercise programs. An electronic physical activity monitor was attached to a belt worn on the left side of the body throughout the day. Daily values for mean ambient temperature, duration of bright sunshine, mean wind speed, mean relative humidity, and precipitation were obtained from local meteorological stations. The day length was calculated from times of sunrise and sunset. Based on the entire group of 41 subjects (ensemble average), a subject's step count per day decreased exponentially with increasing precipitation (r2=0.19, P<0.05). On days when precipitation was <1 mm, the step count increased with the mean ambient temperature over the range of -2 to 17 degrees C, but decreased over the range 17-29 degrees C. The daily step count also tended to increase with day length, but the regression coefficient of determination attributable to step count and mean ambient temperature (r2=0.32, P<0.05) exceeded that linking the step count and day length (r2=0.13, P<0.05). The influence of other meteorological factors was small (r2

Our findings indicate that DTW is associated with prefrontal activation among older adults with mild cognitive impairment. The brain activation during DTW was correlated with executive function. Additional studies are necessary to elucidate the effects of cognitive impairment on the association between prefrontal activity and walking under various conditions.

Objective: The clinical relationship between brain-derived neurotrophic factor (BDNF) and cognitive function or mild cognitive impairment (MCI) is not well-understood. The purpose of this study was to identify the relationship between serum BDNF and cognitive function and MCI, and determine whether serum BDNF level might be a useful biomarker for assessing risk for MCI in older people.Materials and Methods: A total of 4463 individuals aged 65 years or older (mean age 72 years) participating in the study. We measured performance in a battery of neuropsychological and cognitive function tests; serum BDNF concentration.Results: Eight hundred twenty-seven participants (18.8%) had MCI. After adjustment for sex, age, education level, diabetes, and current smoking, serum BDNF was associated with poorer performance in the story memory, and digit symbol substitution task scores. Serum BDNF was marginally associated with the presence of MCI (odds ratio, 95% confidence interval: 1.41, 1.00–1.99) when BDNF was 1.5 SD lower than the mean value standardized for sex and age, education level, diabetes, and current smoking.Conclusion: Low serum BDNF was associated with lower cognitive test scores and MCI. Future prospective studies should establish the discriminative value of serum BDNF for the risk of MCI.

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