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Abstract Background Fertile women may be encouraged to use contraception during clinical trials to avoid potential drug effects on fetuses. However, hormonal contraception interferes with pharmacokinetics and pharmacodynamics and modifies internal milieus. Macrophages depend on the milieu to which they are exposed. Therefore, we assessed whether macrophage function would be affected by the use of combined oral contraceptives (OCs) and if this influence depended on the androgenic or non-androgenic properties of progestin. Methods Healthy adult women were enrolled and stratified into two groups: women who did not use OCs (Fs) and women treated with OCs (FOCs). FOCs were further stratified as a function of androgenic (FOCA+) and non-androgenic (FOCA-) properties of progestins. Routine hematological, biochemical, inflammatory and endothelial dysfunction parameters were measured. Monocyte-derived macrophages (MDMs) were evaluated for the expression and activity of estrogen receptors and androgen receptors, and release of tumor necrosis factor α (TNFα) was measured from unstimulated and lipopolysaccharide-stimulated cells. Results As is already known, the use of OCs changed numerous parameters: the number of lymphocytes, iron levels, total iron-binding capacity of transferrin, triglycerides, high-density lipoprotein, total cholesterol, and C-reactive protein increased, while prothrombin time and alkaline phosphatase decreased. Hormonal levels also varied: cortisol was higher in FOCs, while luteinizing hormone, follicle-stimulating hormone, and testosterone were lower in FOCs. Asymmetric dimethylarginine, an index of endothelial function, was lower in FOC than in Fs, as were cysteine and bilirubin. The androgenic properties of progestins affected the activity of OCs: in particular, white blood cell count, hemoglobin, high-density lipoprotein and calcium were higher in FOCA- than in FOCA+, whereas percentage oxygen saturation and γ-glutamyl transpeptidase were lower in FOCA- than in FOCA+. Importantly, FOCs had a lower global DNA methylation, indicating that OC may have epigenetic effects on gene expression. OC did not modify the expression of androgen receptor but increased estrogen receptor α expression, more considerably in FOCA+, and decreased estrogen receptor β, more considerably in FOCA-. Importantly, the activation state of estrogen receptor β in FOCs was decreased, while estrogen receptor α was not active in either Fs or FOCs. Unstimulated MDMs obtained from FOCs showed higher release of TNFα in comparison with Fs. After lipopolysaccharide stimulation, the release of TNFα was significantly higher in Fs than in FOCs. Conclusions OC use induced many changes in hematological and plasmatic markers, modifying hormonal levels, endothelial function, inflammation index and some redox state parameters, producing a perturbation of the internal milieu that impacted macrophagic function. In fact, different levels of estrogen receptor expression and release of TNFα were observed in macrophages derived from OC users. Some of the above activities were linked to the androgenic properties of progestin. Even though it is not known whether these effects are reversible, the results indicate that to avoid potential skewing of results only a single type of OC should be used during a single clinical trial.

Tumour-induced osteomalacia is a paraneoplastic syndrome wherein bone is affected by a hormone from a tumour that causes renal phosphate wasting and hypophosphataemia. Here, we present the case of a 31-year-old man who has been suffering from generalised bone pains and a spine deformity that led to loss of height. Pertinent findings are low serum phosphorus, low vitamin D and decreased bone mineral density. These findings led to a diagnosis of osteomalacia. However, the finding of an oral mass raised some questions as to what role it plays in the patient's disease. It was suspected that the oral mass (fibroma) was producing a hormone that led to renal phosphate wasting, hypophosphataemia and then osteomalacia. This hypothesis was proven after surgical removal of the mass led to normalisation of the metabolic derangements and eventually led to a resolution of the bone pains., Competing Interests: Conflicts of Interest: None declared., (2017 BMJ Publishing Group Ltd.)

The effects of short- and long-term salinisation were studied by comparing tomato growth on a soil exposed to one-season salinisation (short term) vs growth on a soil exposed to >20 years salinisation (long term). Remarkable differences were associated to substantial modifications of the soil physical-chemical characteristics in the root zone, including deteriorated structure, reduced infiltration properties and increased pH. Fresh yield, fruit number and fruit weight were similarly affected by short- and long-term salinisation. In contrast, the marketable yield was significantly lower in the long-term salinised soil - a response that was also associated to nutritional imbalance (mainly referred to P and K). As reported for plants growing under oxygen deprivation stress, the antioxidant capacity of the water soluble fraction of salinised tomato fruits was enhanced by short-term salinisation, also. Overall, long-term salinisation may cause physiological imbalances and yield reductions that cannot be solely attributed to hyperosmotic stress and ionic toxicity. Therefore, the ability of plants to cope with nutritional deficiency and withstand high pH and anoxia may be important traits that should be considered to improve plant tolerance to long-term salinised soils.

A total of 9 participants with right-hemisphere stroke performed a new virtual reality (VR) wheelchair navigation test of lateralized spatial attention and neglect. The test consists of a virtual path along which participants navigate (or are navigated) as they name virtual objects encountered. There are 4 VR conditions, obtained by crossing the factors array complexity and driver. Participants performed the VR task, a real-life wheelchair navigation task, and a battery of attention and neglect tests. The VR test showed sensitivity to both array complexity and driver, exhibited strong correlations with the wheelchair navigation test, and detected lateralized attention deficits in mild patients. The VR task thus shows promise as a sensitive, efficient measure of real-life navigation.