Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial.

BACKGROUND: In the HD14 trial, 2×BEACOPPescalated+2×ABVD (2+2) has improved the primary outcome. Compared with 4×ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility. PATIENTS AND METHODS: Women≤45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated. RESULTS: Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A=ABVD: 137, B=2+2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (≤12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P=0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio=12.87, P=0.001). Severe menopausal symptoms were frequent in women≥30 years (A: 21%, B: 25%). CONCLUSIONS: Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.

Rain, winds and haze during the Huygens probe's descent to Titan's surface.

The irreversible conversion of methane into higher hydrocarbons in Titan's stratosphere implies a surface or subsurface methane reservoir. Recent measurements from the cameras aboard the Cassini orbiter fail to see a global reservoir, but the methane and smog in Titan's atmosphere impedes the search for hydrocarbons on the surface. Here we report spectra and high-resolution images obtained by the Huygens Probe Descent Imager/Spectral Radiometer instrument in Titan's atmosphere. Although these images do not show liquid hydrocarbon pools on the surface, they do reveal the traces of once flowing liquid. Surprisingly like Earth, the brighter highland regions show complex systems draining into flat, dark lowlands. Images taken after landing are of a dry riverbed. The infrared reflectance spectrum measured for the surface is unlike any other in the Solar System; there is a red slope in the optical range that is consistent with an organic material such as tholins, and absorption from water ice is seen. However, a blue slope in the near-infrared suggests another, unknown constituent. The number density of haze particles increases by a factor of just a few from an altitude of 150 km to the surface, with no clear space below the tropopause. The methane relative humidity near the surface is 50 per cent.

Cell-free DNA release under psychosocial and physical stress conditions.

The understanding of mechanisms linking psychological stress to disease risk depend on reliable stress biomarkers. Circulating cell-free DNA (cfDNA) has emerged as a potential biomarker of cellular stress, aging, inflammatory processes, and cell death. Recent studies indicated that psychosocial stress and physical exercise might also influence its release. We compared the effects of acute psychosocial and physical exercise stress on cfDNA release by exposing 20 young, healthy men to both an acute psychosocial laboratory stressor and an acute physical exercise stressor. Venous blood and saliva samples were collected before and after stress exposure. Cell-free DNA was extracted from plasma and quantified by qPCR. Furthermore, cfDNA fragment length was analyzed and cfDNA methylation patterns were assayed across time. In addition, release of stress hormones and subjective stress responses were measured. Results showed a twofold increase of cfDNA after TSST and fivefold increase after exhaustive treadmill exercise, with an overabundance of shorter cfDNA fragments after physical exhaustion. Interestingly, cell-free mitochondrial DNA showed similar increase after both stress paradigms. Furthermore, cfDNA methylation signatures-used here as a marker for diverse cellular origin-were significantly different post stress tests. While DNA methylation decreased immediately after psychosocial stress, it increased after physical stress, suggesting different cellular sources of active DNA release. In summary, our results suggest stimulus and cell-specific regulation of cfDNA release. Whereas the functional role of stress-associated cfDNA release remains elusive, it might serve as a valuable biomarker in molecular stress research as a part of the psychophysiological stress response.