The PinK Study - Methodology of the Follow-up Survey of a Cohort Study of Couples Undergoing Fertility Treatment

The paper describes the follow-up survey of the PinK study 'Paare in Kinderwunschbehandlung' (couples undergoing fertility treatment). This interdisciplinary study aims at a broader and better understanding of the situation of couples with an unfulfilled desire to have a child. The focus in the follow-up survey is on the situation of the couples one year after their first visit to a fertility clinic in Rhineland-Palatinate or in the capital of Hesse, Wiesbaden. Approximately one year after the baseline survey, self-administered questionnaires were sent to respondents who had signed a written agreement to remain in the study. The field period lasted from June 2013 to August 2014. The final sample consists of 140 women and 93 men. In 89 couples both partners participated. The longitudinal data set includes 224 respondents. The share of baseline survey participants who also participated in the follow-up is 39.6 %. This report describes the study design and materials for the follow-up as well as the sample and analyses the selectivity of dropouts from the baseline sample

Fine tuning Exo2, a small molecule inhibitor of secretion and retrograde trafficking pathways in mammalian cells

The small molecule 4-hydroxy-3-methoxybenzaldehyde (5,6,7,8-tetrahydro[1]benzothieno[2,3- d]pyrimidin-4-yl)hydrazone (Exo2) stimulates morphological changes at the mammalian Golgi and trans-Golgi network that are virtually indistinguishable from those induced by brefeldin A. Both brefeldin A and Exo2 protect cells from intoxication by Shiga(-like) toxins by acting on other targets that operate at the early endosome, but do so at the cost of high toxicity to target cells. The advantage of Exo2 is that it is much more amenable to chemical modification and here we report a range of Exo2 analogues produced by modifying the tetrahydrobenzothienopyrimidine core, the vanillin moiety and the hydrazone bond that links these two. These compounds were examined for the morphological changes they stimulated at the Golgi stack, the trans Golgi network and the transferrin receptor-positive early endosomes and this activity correlated with their inherent toxicity towards the protein manufacturing ability of the cell and their protective effect against toxin challenge. We have developed derivatives that can separate organelle morphology, target specificity, innate toxicity and toxin protection. Our results provide unique compounds with low toxicity and enhanced specificity to unpick the complexity of membrane trafficking networks

Non-professional phagocytosis: a general feature of normal tissue cells

Non-professional phagocytosis by cancer cells has been described for decades. Recently, non-professional phagocytosis by normal tissue cells has been reported, which prompted us to take a closer look at this phenomenon. Non-professional phagocytosis was studied by staining cultured cells with live-cell staining dyes or by staining paraffin-embedded tissues by immunohistochemistry. Here, we report that each of 21 normal tissue cell lines from seven different organs was capable of phagocytosis, including ex vivo cell cultures examined before the 3rd passage as well as the primary and virus-transformed cell lines. We extended our analysis to an in vivo setting, and we found the occurrence of non-professional phagocytosis in healthy skin biopsies immediately after resection. Using dystrophin immunohistochemistry for membrane staining, human post-infarction myocardial tissue was assessed. We found prominent signs of non-professional phagocytosis at the transition zone of healthy and infarcted myocardia. Taken together, our findings suggest that non-professional phagocytosis is a general feature of normal tissue cells

Graphene modification for preparation of stable nanofluids

International audienceCarbon-based nanomaterials, such as carbon nanotubes or graphene, are recognized to be excellentcandidates for high performance materials. Graphene which is a layer of sp2 hybridized carbon atomswith a thickness of only one atom possesses various magnificent properties that are not shared byother materials [1]. Their excellent intrinsic thermal properties have, in particular, led a stronginterest for heat transfer applications [2]. However, dispersion of such material in water to preparestable nanofluids is highly difficult. And the dispersion issue is pointed out to be the main reason forthe reported disappointing and contradictory results in term of performance of such nanofluids [3].Indeed carbon nanoparticles are usually strongly hydrophobic and tend to separate from the liquidmedium, aggregate and sediment. Graphene being a new material, its efficient and controlled surfacemodification is still challenging. Our paper proposes different ways to chemically modify theproperties of graphenic materials in order to increase their hydrophilic character improving that waytheir dispersion. Chemical reactivity of graphene upon the applied treatments was deeply analyzedbased on the carried out multi-scale characterization of the modified graphene. We will discussgraphene reactivity in comparison with other nanostructured carbon materials. Rheologicalproperties of the prepared graphene dispersions will be presented and discussed regarding thepractical use of such dispersions under flowing conditions for heat transfer applications

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

International audienceBACKGROUND Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.OBJECTIVES This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.METHODS In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.RESULTS Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 +/- 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across alt patients, mean z-scores for T1 and T2 values were 2.9 +/- 1.9 (p < 0.001) and 2.2 +/- 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1(1,079.0 +/- 55.5 ms vs. 1,000.3 +/- 221 ms; p < 0.001) and 12 (56.2 +/- 4.9 ms vs. 49.8 +/- 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91(95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.CONCLUSIONS The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients&nbsp;With&nbsp;Immune Checkpoint Inhibitor-Associated Myocarditis.

Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction&nbsp;&lt;55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p&nbsp;&lt;&nbsp;0.001) and 2.2 ± 2.1 (p&nbsp;&lt;&nbsp;0.001), respectively. On Siemens 1.5-T scanner (n&nbsp;=&nbsp;67), native T1 (1,079.0 ± 55.5&nbsp;ms vs. 1,000.3 ± 22.1&nbsp;ms; p&nbsp;&lt;&nbsp;0.001) and T2 (56.2 ± 4.9&nbsp;ms vs. 49.8 ± 2.2&nbsp;ms; p&nbsp;&lt;&nbsp;0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p&nbsp;=&nbsp;0.004) but not T2 values were independently associated with subsequent MACE.The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis

Effect of a tree mixture and water availability on soil nutrients and extracellular enzyme activities along the soil profile in an experimental forest

An increasing number of studies demonstrate that tree species biodiversity can affect primary productivity and nutrient cycling in forests due to several factors, such as complementarity, facilitation or selection effects. For instance, resource partitioning in soils has been found to allow a more optimized nutrient uptake in mixed species plots compared with monocultures. However, how these effects will be modified by climate change – such as water availability – is not as well understood, especially in deep soil layers. Therefore, we specifically asked how water availability may influence the effect of tree mixtures on soil microorganism activity by measuring extracellular enzyme activities (EEAs) and available nutrients along the soil profile (down to 90 cm) in a 10-year-old plantation in southwestern France, which manipulates tree species composition (Pinus pinaster and Betula pendula, in monocultures and in mixed plots) and irrigation. Our results showed that EEAs directly depend on tree species composition and water conditions in interaction with soil depth; we found a positive effect of mixing birch and pine on carbon and nitrogen-related EEAs at an intermediate soil depth (15–30 cm soil layer), while the effect of increasing water availability increased phosphorus-related EEAs mostly in the upper soil layers (0–30 cm). However, we found no significant interactive effect between tree diversity and water availability on EEAs, underlying that the negative effect of lower water availability cannot be offset by the positive effect of mixing tree species. Differences in EEAs and available nutrients along the soil profile highlight the importance to look at different soil depths to better understand how nutrient cycling may be affected by increasing tree diversity and changes in water availability.Diversité et Productivité des forêTs impactées par le Changement Climatiqu

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients&nbsp;With&nbsp;Immune Checkpoint Inhibitor-Associated Myocarditis.

Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction&nbsp;&lt;55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p&nbsp;&lt;&nbsp;0.001) and 2.2 ± 2.1 (p&nbsp;&lt;&nbsp;0.001), respectively. On Siemens 1.5-T scanner (n&nbsp;=&nbsp;67), native T1 (1,079.0 ± 55.5&nbsp;ms vs. 1,000.3 ± 22.1&nbsp;ms; p&nbsp;&lt;&nbsp;0.001) and T2 (56.2 ± 4.9&nbsp;ms vs. 49.8 ± 2.2&nbsp;ms; p&nbsp;&lt;&nbsp;0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p&nbsp;=&nbsp;0.004) but not T2 values were independently associated with subsequent MACE.The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis