Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.     

Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer—results from the GeparQuattro study (GBG 40)

Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline?Ctaxane?Ctrastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana^? automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P?=?0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2?C0.9), P?=?0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r?=?0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r?=?0.892) and after treatment (r?=?0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P?=?0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.     

Analysis of volatile organic compounds (VOCs) in the headspace of NCI-H1666 lung cancer cells

Analysis of volatile organic compounds (VOCs) provides an elegant approach for cancer screening and disease monitoring, whose use is currently limited by a lack of validated cancer-derived metabolites, which may serve as biomarkers. The aim of the experiments presented here was to investigate the release and consumption of VOCs from the non small cell lung cancer cell line NCI-H1666, which was originally derived from a bronchoalveolar carcinoma.Following detachment by trypsinization suspended cells were incubated in a sealed fermenter for 21 hours. 200 ml of headspace from the cell culture were sampled, diluted with dry, highly purified air and preconcentrated by adsorption on three different solid sorbents with increasing adsorption strength. VOC-analysis was performed by thermodesorption-gas chromatography mass spectrometry (TD-GC-MS). In contrast to our previous studies experiments with NCI-H1666 cells only confirmed the consumption of several aldehydes, n-butyl acetate and the ethers methyl tert-butyl ether and ethyl tert-butyl ether, but no unequivocal release of VOCs was observed. Together with our previously published work these data indicate that the consumption of certain VOCs is commonly observed while their release shows cell line-restricted patterns, whose underlying causes are unknown.     

Alcohol consumption and hepatic fibrosis affect the fatty acid composition of red blood cells and their susceptibility to lipid peroxidation

Erythrocytes from alcoholics with and without liver cirrhosis and from rats treated either with ethanol or thioacetamide, the latter treatment resulting in hepatic fibrosis, were analysed for their membrane fatty acid composition and their susceptibility to lipid peroxidation. Red cells containing less arachidonic acid than controls, as found in alcoholics with liver cirrhosis, were less susceptible to lipid peroxidation than controls. This observation was confirmed by experiments with rat erythrocytes obtained from animals with hepatic fibrosis. However, red cells containing less linoleic acid than controls, as found in alcoholics without liver cirrhosis, exhibited a normal degree of lipid peroxidation upon oxidant stress induced by hydrogen peroxide. The results demonstrated that in red cells only fatty acids with four double bonds seem to be involved in membrane peroxidation reactions under the condition chosen. This observation might be of relevance for in vivo aging of red cells.Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday     

Estimating human mobility in Holocene Western Eurasia with large-scale ancient genomic data

The recent increase in openly available ancient human DNA samples allows for large-scale meta-analysis applications. Trans-generational past human mobility is one of the key aspects that ancient genomics can contribute to since changes in genetic ancestry—unlike cultural changes seen in the archaeological record—necessarily reflect movements of people. Here, we present an algorithm for spatiotemporal mapping of genetic profiles, which allow for direct estimates of past human mobility from large ancient genomic datasets. The key idea of the method is to derive a spatial probability surface of genetic similarity for each individual in its respective past. This is achieved by first creating an interpolated ancestry field through space and time based on multivariate statistics and Gaussian process regression and then using this field to map the ancient individuals into space according to their genetic profile. We apply this algorithm to a dataset of 3138 aDNA samples with genome-wide data from Western Eurasia in the last 10,000 y. Finally, we condense this sample-wise record with a simple summary statistic into a diachronic measure of mobility for subregions in Western, Central, and Southern Europe. For regions and periods with sufficient data coverage, our similarity surfaces and mobility estimates show general concordance with previous results and provide a meta-perspective of genetic changes and human mobility.

All human behavior is spatial behavior, and spatial perception and interaction are deeply rooted in the human mind. Understanding movements in space—mobility—on different orders of magnitude is therefore a major component for understanding human behavior throughout history (1), from the Iceman’s quest through the Ötztal Alps, to the Viking expansion even beyond Medieval Europe, and maybe eventually humankind’s journey to the stars.Anthropological theory provides different concepts and categories to classify mobility. Mobility can be permanent or cyclical, a group property or individual behavior, and finally motivated by economic, social, or cultural incentives. It has complex implications for the formation, perception, and interaction of identity (2–4). Migration is an especially challenging and controversial topic (5, 6) as it is notoriously difficult to prove and to uncover its causes among the interdependencies of microprocesses and macroprocesses (7). Narratives of migration are particularly vulnerable to political instrumentalization (8).The field of archaeogenetics now provides a perspective on mobility, which is at its very core influenced by population genetics theory. The emergence, change, and distribution of human ancestry components—mediated by the mobility of their hosts—are in fact some of its most important research questions (e.g., refs. 9–11), causing fruitful and corrective friction with the humanities (12–14). While so far much archaeogenetic research focuses on particular cultural–historical contexts, the recent growth of published ancient DNA samples from all around the world enables a unique category of quantitative meta-analysis.Large, explicitly spatiotemporal datasets have been part of population genetics research for a long time already (15), sometimes even with a focus on mobility quantification (16–19). But to our knowledge, only few attempts have been made to systematically derive a continuous, large-scale and diachronic measure of human mobility with ancient genetic data. These are most notably a pioneering publication by Loog et al. (20) and another approach by Racimo et al. (21). Loog et al. measure mobility in prehistoric Europe by comparing the distance matrix correlation among spatial, temporal, and genetic distance for aDNA samples in moving 4,000-y windows. As a result, they generate an unscaled mobility proxy curve that indicates elevated levels of mobility correlating with the Neolithic expansion, the Steppe migration, and, finally, the European Iron Age. Racimo et al., on the other hand, employ admixture analysis to model the dynamics of specific ancestry components through time: Mesolithic hunter-gatherers, Neolithic farmers with ancestry originating in the Near East, and Yamnaya steppe herders, arriving in Europe during the third millennium BC. They derive mobility as a wave front speed of surpassed ancestry component thresholds. To overcome sample sparsity and to correlate the arrival of certain ancestry components with biogeographic metrics, they use Gaussian process regression for the interpolation of relative ancestry component occurrence—an idea we also took as a starting point for our proposed mobility estimation method.In this paper, we present an algorithm to estimate past human mobility on the individual level. For each individual, we determine a probability distribution in space, which yields locations of likely genetic similarity to the sample in question. We call this the similarity probability surface, which, as we show, is generally informative on where an individual’s ancestors might have lived. The distance between the location where an individual was buried and a point of maximum likelihood in the similarity surface serves us as a simplified proxy for personal mobility in an individual’s (or their ancestors’) lifetime. We apply this algorithm to several thousand previously published ancient genomes from Western Eurasia dating from between 8000 BC and 2000 AD (excluding modern genomes) taken from the Allen Ancient DNA Resource (AADR) (22). And, we show that, while the average results largely match expectations including known and large-scale movements at the beginning and end of the Neolithic, these large-scale patterns are accompanied by considerable individual-level heterogeneity.     

Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD

Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na⁺ homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α₂-isoform of Na⁺/K⁺-ATPase (α₂NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α₂NaKA. Thus, α₂NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α₂NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α₂NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke.     

Soiled saris: a vector of disease transmission?

We examined the relationship between uses of the sari that are potential health hazards and episodes of diarrhoea in children younger than 6 years in 247 families living in 51 slums in Dhaka, Bangladesh. These misuses appeared to be common (median of three per observation period) and were largely unrecognized by the women as possible sources of disease transmission. There appeared to be a positive correlation between the number of misuses of the sari and episodes of childhood diarrhoea.     

Arabinoxylan-Based Microcapsules Being Loaded with Bee Products as Bioactive Food Components Are Able to Modulate the Cell Migration and Inflammatory Response—In Vitro Study

The aim of the research was to use bioactive heteropolysaccharides isolated from rye bran to obtain innovative systems for the controlled release of bioactive compounds. The core of the obtained encapsulates was honey and royal jelly. It was shown for the first time that preparations effectively ameliorated inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, decreasing the secretion of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and nitric oxide (NO). The in vitro digestion process revealed that bee products’ encapsulates were stronger oxidative stress reducers and had sustained ability to reduction in inflammation state mediators. The lack of inhibitory effect on migration rate of human microvascular endothelial cells (HMEC-1) endothelial cells and mouse embryonic fibroblasts (NIH-3T3), both cell models involved in wound healing process, additionally identified these preparations as agents potentially used in the management of inflammatory response. In the process of a simulated digestion in vitro, the innovative microcapsules showed 85% higher biostability and two to ten times better bioavailability, compared to natural bee products.     

Die Praxis der Blutübertragung mit Technischen und Therapeutischen Verbesserungen Durch Vetren und den Infusor D.R.P.

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