Background Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. Methods We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials - the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. Results Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. Conclusions In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617 .).
The morphological change of silicon macropore arrays formed by metal-assisted chemical etching using shape-controlled Au thin film arrays was investigated during anisotropic chemical etching in tetramethylammonium hydroxide (TMAH) aqueous solution. After the deposition of Au as the etching catalyst on (111) silicon through a honeycomb mask prepared by sphere lithography, the specimens were etched in a mixed solution of HF and H2O2 at room temperature, resulting in the formation of ordered macropores in silicon along the  direction, which is not achievable by conventional chemical etching without a catalyst. In the anisotropic etching in TMAH, the macropores changed from being circular to being hexagonal and finally to being triangular, owing to the difference in etching rate between the crystal planes.
Carotenoids are protective pigments present in many aquatic organisms that reduce the photooxidative stress induced by short-wavelenght solar radiation, yet increase their susceptibility to predators. Arctodiaptomus spinosus, a calanoid copepod typically found in many fishless shallow soda lakes, shows large between-lake differences in pigmentation. Here, we attribute these differences to the environmental state of these ecosystems, namely, ‘dark water’ lakes with submersed vegetation and turbid ‘white’ lakes lacking macrophytes. Copepod carotenoid concentration in the turbid ‘white’ lakes was significantly (about 20-fold) higher than in the ‘dark water’ ones, although the latter systems were characterized by higher transparency. In addition, males had on a dry weight basis around three times higher carotenoid concentrations than females. Mycosporine-like amino acids (direct UV screening substances) were found in all cases, but in low concentration. The environmental conditions in these ecosystems were largely shaped by the presence/absence of submersed macrophytes Thus, in the turbid lakes, the strong wind-driven mixis allows for copepods to be brought to the surface and being exposed to solar radiation, whereas in ‘dark water’ ones, macrophytes reduce water turbulence and additionally provide shelter. Our results explain the counter-intuitive notion of strong red pigmentation in copepods from a turbid ecosystem and suggest that factors other than high UV transparency favor carotenoid accumulation in zooplankton.
To date, gold nanoparticles (AuNPs) have been investigated for diverse bioapplications. Generally, AuNPs are engineered to possess surface coating with organic/inorganic shells to increase colloidal stability in biological solutions and to facilitate chemical conjugation. In the present study, we developed a strategy to prepare dextran-coated AuNPs with control over its size by simply boiling an aqueous solution of Au salt and dextran, in which dextran serves as both reducing agent for AuNP (Au(0)) formation from Au(III) and AuNP surface coating material. The prepared dextran-coated AuNPs (dAuNPs) maintained its colloidal stability under high temperature, high salt concentration, and extreme pH. Importantly, the dAuNP remarkably improved efficacy of an anti-cancer agent, doxorubicin (Dox), when harnessed as a Dox delivery carrier. The half-maximal inhibitory concentration (EC50) of Dox-conjugated dAuNP with diameter of 170 nm was ∼9 pM in HeLa cells, which was 1.1 × 10(5) times lower than that of free Dox and lower than any previously reported values of Dox-nanoparticle complex. Interestingly, smaller AuNPs with 30 and 70 nm showed about 10 times higher EC50 than 170 nm AuNPs when treated to HeLa cells after conjugation with Dox. To achieve high cytotoxicity as cancer therapeutics, Dox should be delivered into nucleus to intercalate with DNA double helix. We show here that Dox-AuNPs was far more efficient as an anti-cancer drug than free Dox by releasing from AuNPs through spontaneous degradation of dextran, allowing free diffusion and nuclear uptake of Dox. We also revealed that larger AuNPs with lower degree of dextran crosslinking promoted faster degradation of dextran shells.
A study was undertaken to determine activity concentrations for (134)Caesium, (137)Caesium and (210)Polonium in New Zealand seafood, and establish if activity concentrations varied with respect to species/ecological niche and coastal region. Thirty seafood samples were obtained from six fishing regions of New Zealand along with a further six samples of two commercially important species (hoki and arrow squid) with well-defined fisheries. (134)Caesium was not detected in any sample. (137)Caesium was detected in 47% of samples, predominantly in pelagic fish species, with most activities at a trace level. Detections of (137)Caesium were evenly distributed across all regions. Activity concentrations were consistent with those expected from the oceanic inventory representing residual fallout from global nuclear testing. (210)Polonium was detected above the minimum detectable concentration in 33 (92%) of the analysed samples. Molluscs displayed significantly elevated activity concentrations relative to all other species groups. No significant regional variation in activity concentrations were determined. Two dose assessment models for high seafood consumers were undertaken. Dose contribution from (137)Caesium was minimal and far below the dose exemption limit of 1 mSv/year. Exposure to (210)Polonium was significant in high seafood consumers at 0.44-0.77 mSv/year (5th-95th percentile). (137)Caesium is concluded to be a valuable sentinel radionuclide for monitoring anthropogenic releases, such as global fallout and reactor releases, in the marine environment. (210)Polonium is of importance as a natural radionuclide sentinel due to its high contribution to dietary committed dose in seafood consumers.
This study is dedicated to the environmental monitoring of radionuclides released in the course of the Fukushima nuclear accident. The activity concentrations of β(-) -emitting (90)Sr and β(-)/γ-emitting (134)Cs and (137)Cs from several hot spots in Japan were determined in soil and vegetation samples. The (90)Sr contamination levels of the samples were relatively low and did not exceed the Bq⋅g(-1) range. They were up four orders of magnitude lower than the respective (137)Cs levels. This study, therefore, experimentally confirms previous predictions indicating a low release of (90)Sr from the Fukushima reactors, due to its low volatility. The radiocesium contamination could be clearly attributed to the Fukushima nuclear accident via its activity ratio fingerprint ((134)Cs/(137)Cs). Although the correlation between (90)Sr and (137)Cs is relatively weak, the data set suggests an intrinsic coexistence of both radionuclides in the contaminations caused by the Fukushima nuclear accident. This observation is of great importance not only for remediation campaigns but also for the current food monitoring campaigns, which currently rely on the assumption that the activity concentrations of β(-)-emitting (90)Sr (which is relatively laborious to determine) is not higher than 10% of the level of γ-emitting (137)Cs (which can be measured quickly). This assumption could be confirmed for the samples investigated herein.
THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.
Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment.
We describe spatial patterns in environmental injustice and inequality for residential outdoor nitrogen dioxide (NO2) concentrations in the contiguous United States. Our approach employs Census demographic data and a recently published high-resolution dataset of outdoor NO2 concentrations. Nationally, population-weighted mean NO2 concentrations are 4.6 ppb (38%, p<0.01) higher for nonwhites than for whites. The environmental health implications of that concentration disparity are compelling. For example, we estimate that reducing nonwhites' NO2 concentrations to levels experienced by whites would reduce Ischemic Heart Disease (IHD) mortality by ∼7,000 deaths per year, which is equivalent to 16 million people increasing their physical activity level from inactive (0 hours/week of physical activity) to sufficiently active (>2.5 hours/week of physical activity). Inequality for NO2 concentration is greater than inequality for income (Atkinson Index: 0.11 versus 0.08). Low-income nonwhite young children and elderly people are disproportionately exposed to residential outdoor NO2. Our findings establish a national context for previous work that has documented air pollution environmental injustice and inequality within individual US metropolitan areas and regions. Results given here can aid policy-makers in identifying locations with high environmental injustice and inequality. For example, states with both high injustice and high inequality (top quintile) for outdoor residential NO2 include New York, Michigan, and Wisconsin.
The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4-8 mM). ACh is extremely well conserved in royal jelly or brood food because of the acidic pH of 4.0. This condition protects ACh from degradation thus ensuring delivery of intact ACh to larvae. Raising the pH to ≥5.5 and applying cholinesterase reduced the content of ACh substantially (by 75-90%) in larval food. When this manipulated brood was tested in artificial larval breeding experiments, the survival rate was higher with food supplemented by 100% with ACh (6 mM) than with food not supplemented with ACh. ACh release from the hypopharyngeal gland and its content in brood food declined by 80%, when honeybee colonies were exposed for 4 weeks to high concentrations of the neonicotinoids clothianidin (100 parts per billion [ppb]) or thiacloprid (8,800 ppb). Under these conditions the secretory cells of the gland were markedly damaged and brood development was severely compromised. Even field-relevant low concentrations of thiacloprid (200 ppb) or clothianidin (1 and 10 ppb) reduced ACh level in the brood food and showed initial adverse effects on brood development. Our findings indicate a hitherto unknown target of neonicotinoids to induce adverse effects on non-neuronal ACh which should be considered when re-assessing the environmental risks of these compounds. To our knowledge this is a new biological mechanism, and we suggest that, in addition to their well documented neurotoxic effects, neonicotinoids may contribute to honeybee colony losses consecutive to a reduction of the ACh content in the brood food.