Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581]

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m(2 )and 10.72 nmol/L, respectively

New understandings of the genetic basis of isolated idiopathic central hypogonadism

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network

Extracellular Superoxide Dismutase Protects Histoplasma Yeast Cells from Host-Derived Oxidative Stress

In order to establish infections within the mammalian host, pathogens must protect themselves against toxic reactive oxygen species produced by phagocytes of the immune system. The fungal pathogen Histoplasma capsulatum infects both neutrophils and macrophages but the mechanisms enabling Histoplasma yeasts to survive in these phagocytes have not been fully elucidated. We show that Histoplasma yeasts produce a superoxide dismutase (Sod3) and direct it to the extracellular environment via N-terminal and C-terminal signals which promote its secretion and association with the yeast cell surface. This localization permits Sod3 to protect yeasts specifically from exogenous superoxide whereas amelioration of endogenous reactive oxygen depends on intracellular dismutases such as Sod1. While infection of resting macrophages by Histoplasma does not stimulate the phagocyte oxidative burst, interaction with polymorphonuclear leukocytes (PMNs) and cytokine-activated macrophages triggers production of reactive oxygen species (ROS). Histoplasma yeasts producing Sod3 survive co-incubation with these phagocytes but yeasts lacking Sod3 are rapidly eliminated through oxidative killing similar to the effect of phagocytes on Candida albicans yeasts. The protection provided by Sod3 against host-derived ROS extends in vivo. Without Sod3, Histoplasma yeasts are attenuated in their ability to establish respiratory infections and are rapidly cleared with the onset of adaptive immunity. The virulence of Sod3-deficient yeasts is restored in murine hosts unable to produce superoxide due to loss of the NADPH-oxidase function. These results demonstrate that phagocyte-produced ROS contributes to the immune response to Histoplasma and that Sod3 facilitates Histoplasma pathogenesis by detoxifying host-derived reactive oxygen thereby enabling Histoplasma survival

Stressed out symbiotes:hypotheses for the influence of abiotic stress on arbuscular mycorrhizal fungi

Abiotic stress is a widespread threat to both plant and soil communities. Arbuscular mycorrhizal (AM) fungi can alleviate effects of abiotic stress by improving host plant stress tolerance, but the direct effects of abiotic stress on AM fungi are less well understood. We propose two hypotheses predicting how AM fungi will respond to abiotic stress. The stress exclusion hypothesis predicts that AM fungal abundance and diversity will decrease with persistent abiotic stress. The mycorrhizal stress adaptation hypothesis predicts that AM fungi will evolve in response to abiotic stress to maintain their fitness. We conclude that abiotic stress can have effects on AM fungi independent of the effects on the host plant. AM fungal communities will change in composition in response to abiotic stress, which may mean the loss of important individual species. This could alter feedbacks to the plant community and beyond. AM fungi will adapt to abiotic stress independent of their host plant. The adaptation of AM fungi to abiotic stress should allow the maintenance of the plant-AM fungal mutualism in the face of changing climates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00442-016-3673-7) contains supplementary material, which is available to authorized users

Measurement of the mass difference m(D-s(+))-m(D+) at CDF II

We present a measurement of the mass difference m(D-s(+))-m(D+), where both the D-s(+) and D+ are reconstructed in the phipi(+) decay channel. This measurement uses 11.6 pb(-1) of data collected by CDF II using the new displaced-track trigger. The mass difference is found to be m(D-s(+))-m(D+)=99.41+/-0.38(stat)+/-0.21(syst) MeV/c(2)

Myoelectric Fatigue Profiles of Three Knee Extensor Muscles

Aims of the present study were to: 1) investigate the differences between the myoelectric fatigue profiles of the vasti muscles of the quadriceps during electrically evoked contractions; 2) compare the myoelectric fatigue profiles of the vasti muscles between sedentary subjects and rowers; 3) analyze motor unit activation order during stimulation of the vasti muscles. In nine sedentary subjects and nine rowers surface EMG signals were detected during electrically elicited contractions of the following three muscles: vastus medialis obliquus (VMO), vastus lateralis (VL), and vastus medialis longus (VML). M-waves were recorded as the muscles were stimulated with both variable (increasing-decreasing) and constant stimulation intensities. Changes in M-wave conduction velocity (CV) during trains with non-constant current were adopted for the study of the motor unit recruitment order. Rates of change of myoelectric signal variables were adopted to assess myoelectric manifestations of fatigue during stimulation trains with constant current. We found that: 1) VL muscle was more fatigable than vastus medialis muscles; 2) VL and VML muscles of rowers resulted less fatigable than sedentary subjects; and 3) in the three muscles, motor units tended to be recruited in order of increasing CV and derecruited in order of decreasing CV with increasing/decreasing stimulation current

Effects of Short-Term Dexamethasone Administration on Corticospinal Excitability

Purpose: The short-term administration of glucocorticoids increases maximal voluntary force in healthy humans, but the underlying mechanisms remain poorly understood. The present study investigated the glucocorticoid effects on spinal and corticospinal pathways and on electromechanical properties of the tibialis anterior muscle in response to nerve stimulation. METHODS: Twelve healthy men participated in a single-blind randomized study to receive either dexamethasone (8 mg · d(-1), n = 8 subjects) or placebo (n = 4 subjects) for 7 d. Group Ia afferent and corticospinal pathways were assessed, respectively, by recording the amplitude of the Hoffmann (H) reflex and motor-evoked potential (MEP) by transcranial magnetic stimulation. The ankle dorsiflexor torque and EMG activity during a maximal voluntary contraction (MVC) and muscle twitch evoked by electrical stimulation were also assessed before and after the intervention. RESULTS: The MVC torque (+14%) and the associated tibialis anterior EMG (+16%) increased after glucocorticoid treatment (P < 0.05), whereas muscle twitch parameters did not change (P > 0.05). The H-reflex amplitude did not change (P = 0.58), but the MEP threshold was significantly (P = 0.008) reduced after treatment. Moreover, the slope of the MEP input-output relation and the silent period/MEP ratio increased (P = 0.049) and decreased (P = 0.029), respectively, after treatment. The amount of change in MEP amplitude and MVC torque were positively associated (r(2) = 0.59) for the dexamethasone group. CONCLUSION: This is the first study indicating that short-term glucocorticoid administration in healthy subjects increased corticospinal excitability that contributed to enhance MVC torqu