The short-term effects of high-dose testosterone on sleep,breathing, and function in older men

Androgen therapy may precipitate obstructive sleep apnea in men. Despite increasing androgen use in older men, few studies have examined sleep and breathing. Randomized, double-blind, placebo-controlled studies examining effects of testosterone simultaneously on sleep, breathing, and function in older men are not available. Seventeen community-dwelling healthy men over the age of 60 yr were randomized to receive three injections of im testosterone esters at weekly intervals (500 mg, 250 mg, and 250 mg) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout. Polysomnography, anthropometry, and physical, mental, and metabolic function were assessed at baseline and after each treatment period. Testosterone treatment reduced total time slept ( approximately 1 h), increased the duration of hypoxemia ( approximately 5 min/night), and disrupted breathing during sleep (total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour) (all P < 0.05). Despite expected effects on body composition (increase in total and lean mass, reduction in fat mass, P < 0.05, bioimpedance method), upper airway dimensions did not change (acoustic reflectometry). Driving ability (computer simulation), physical activity (accelerometry, Physical Activity Scale in the Elderly), quality of life (SF36, Functional Outcomes of Sleep Questionnaire), mood (Profile of Mood States Questionnaire), sleepiness (Epworth, Stanford scales), and insulin resistance (homeostasis model) also were not changed by treatment. Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical, mental, or metabolic function. These changes did not appear to be due to upper airway narrowing. Further study of longer-term lower-dose androgen therapy on sleep and breathing is needed to evaluate its safety in older men.     

Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase

Aging is characterized by progressive loss of cognitive and memory functions as well as decrease in physical activities. In the present study, a human neural stem cell line (F3 NSC) over-expressing choline acetyltransferase (F3.ChAT), an enzyme responsible for acetylcholine synthesis, was generated and transplanted in the brain of 18-month-old male ICR mice. Four weeks post-transplantation, neurobehavioral functions, expression of ChAT enzyme, production of acetylcholine and neurotrophic factors, and expression of cholinergic nervous system markers in transplanted animals were investigated. F3.ChAT NSCs markedly improved both the cognitive function and physical activity of aging animals, in parallel with the elevation of brain acetylcholine level. Transplanted F3 and F3.ChAT cells were found to differentiate into neurons and astrocytes, and to produce ChAT proteins. Transplantation of the stem cells increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), enhanced expression of Trk B, and restored host microtubule-associated protein 2 and cholinergic nervous system. The results demonstrate that human NSCs over-expressing ChAT improve cognitive function and physical activity of aging mice, not only by producing ACh directly but also by restoring cholinergic neuronal integrity, which might be mediated by neurotrophins BDNF and NGF.     

Hypofractionated radiotherapy with Tomotherapy for patients with hepatic oligometastases: retrospective analysis of two institutions

To evaluate the efficacy and toxicity for patients with hepatic oligometastases, receiving hypofractionated radiotherapy with Tomotherapy to the liver. A total of 42 patients with 54 hepatic lesions, who had been treated from 2007 to 2011 at two institutions, were retrospectively reviewed for this study. All the patients received radical resections of the primary tumor, and had been presented with one to two hepatic lesions. The radiation dose of 40–75 Gy in 10–20 fractions (median, 50 Gy in 10 fractions) was delivered for the planning target volume. At a median follow-up time of 15 months, 1- and 2-year local control (LC) rates were 59.9 and 49.0 %, respectively. The 1- and 2-year overall survival (OS) rates were 60.0 and 44.0 %, respectively. Maximal tumor diameter of <3 cm and biologically effective dose (BED) of ≥100 Gy_α/β=10 were significantly associated with higher LC and OS. Primary colorectal cancer tended to be associated with higher LC (P = 0.075), and was significantly associated with higher OS (P = 0.037). 12 (28.6 %) of the 42 patients had grade 1–2 toxicities, and grade 3 or higher toxicity did not occur. Hypofractionated radiotherapy with Tomotherapy was safe for patients with hepatic oligometastases. The maximal tumor diameter of <3 cm and BED of ≥100 Gy_α/β=10 were significant prognostic factors for higher local control and survival, and primary colorectal cancer patients had statistically higher overall survival than the others.     

Epigenetic regulation by long noncoding RNAs in plants

Many eukaryotes, including plants, produce a large number of long noncoding RNAs (lncRNAs). Growing number of lncRNAs are being reported to have regulatory roles in various developmental processes. Emerging mechanisms underlying the function of lncRNAs indicate that lncRNAs are versatile regulatory molecules. They function as potent cis- and trans-regulators of gene expression, including the formation of modular scaffolds that recruit chromatin-modifying complexes to target chromatin. LncRNAs have also been reported in plants. Here, we describe our current understanding on potential roles of lncRNA in plants.