Predicting neurodegeneration from sleep related biofluid changes

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances are considered as evidence of an underlying neurodegenerative process. Levels of hormonal sleep-related biomarkers such as melatonin, cortisol and orexin are often abnormal in patients with clinical neurodegenerative diseases, but their relationships with the more standard neurodegenerative biomarkers remain unclear. Similarly, it is unclear whether other chronobiological/circadian biomarkers, such as disrupted clock gene expression, are causal factors or a consequence of neurodegeneration. Current data would suggest that a combination of fluid biomarkers may identify sleep-wake disturbances that are most predictive for the risk of developing neurodegenerative disease with more optimal sensitivity and specificity

The Social Psychology of Religion and Wellbeing: Is a Belief in a God, Good for one’s Wellbeing? An Empirical Inquiry

Objectives: The correlations between religion, age, education, ethnicity, social class, and subjective psychological wellbeing (SWB) of Jamaicans were examined and the predictability of those selected predisposing conditions on SWB were determined.Method: Analysis of the data was by bivariate and multivariate analyses, taken from a nationally representative survey of 1,338 Jamaican adults ≥18 years. The survey was conducted between July and August 2006 by the Centre of Leadership and Governance (CLG), Department of Government, the University of the West Indies, Mona-Jamaica.Findings: The findings indicated that religiosity was positively correlated with SWB as well as ethnicity, education and social class, and that gender was negatively related to SWB. It can be generalized, using multiple regressions, that religiosity, race, gender, education and social class can explain 7.7% of the variance in SWB of Jamaicans. Religiosity was found to be a weak predictor of subjective wellbeing (SWB), (1%), with race contributing 0.4% and gender at 0.3% been among the least suppliers to the model. However, self-reported social class made the most significant contribution to SWB - (3.9%) - along with years of schooling which contributed 2.2%.Conclusion: The study showed that religion provides for a different psychological state for its practitioners as well as influences the general state of wellbeing

Volumetric CT-based segmentation of NSCLC using 3D-Slicer

Accurate volumetric assessment in non-small cell lung cancer (NSCLC) is critical for adequately informing treatments. In this study we assessed the clinical relevance of a semiautomatic computed tomography (CT)-based segmentation method using the competitive region-growing based algorithm, implemented in the free and public available 3D-Slicer software platform. We compared the 3D-Slicer segmented volumes by three independent observers, who segmented the primary tumour of 20 NSCLC patients twice, to manual slice-by-slice delineations of five physicians. Furthermore, we compared all tumour contours to the macroscopic diameter of the tumour in pathology, considered as the “gold standard”. The 3D-Slicer segmented volumes demonstrated high agreement (overlap fractions > 0.90), lower volume variability (p = 0.0003) and smaller uncertainty areas (p = 0.0002), compared to manual slice-by-slice delineations. Furthermore, 3D-Slicer segmentations showed a strong correlation to pathology (r = 0.89, 95%CI, 0.81–0.94). Our results show that semiautomatic 3D-Slicer segmentations can be used for accurate contouring and are more stable than manual delineations. Therefore, 3D-Slicer can be employed as a starting point for treatment decisions or for high-throughput data mining research, such as Radiomics, where manual delineating often represent a time-consuming bottleneck

The modern pollen-vegetation relationship of a tropical forest-savannah mosaic landscape, Ghana, West Africa

Transitions between forest and savannah vegetation types in fossil pollen records are often poorly understood due to over-production by taxa such as Poaceae and a lack of modern pollen-vegetation studies. Here, modern pollen assemblages from within a forest-savannah transition in West Africa are presented and compared, their characteristic taxa discussed, and implications for the fossil record considered. Fifteen artificial pollen traps were deployed for 1 year, to collect pollen rain from three vegetation plots within the forest-savannah transition in Ghana. High percentages of Poaceae and Melastomataceae/Combretaceae were recorded in all three plots. Erythrophleum suaveolens characterised the forest plot, Manilkara obovata the transition plot and Terminalia the savannah plot. The results indicate that Poaceae pollen influx rates provide the best representation of the forest-savannah gradient, and that a Poaceae abundance of >40% should be considered as indicative of savannah-type vegetation in the fossil record

δ18O-inferred salinity from Littorina littorea (L.) gastropods in a Danish shell midden at the Mesolithic–Neolithic transition

Norsminde Fjord has received extensive geoarchaeological investigation, hosting one of the classic Stone Age shell midden sites in Denmark, and one of the best examples of the widespread oyster decline at the Mesolithic–Neolithic transition. Here, intra-shell δ18O (and δ13C) analyses from the common periwinkle Littorina littorea (L.) are used to infer inter-annual environmental changes at the Mesolithic–Neolithic transition (four from each period). This study utilises a modern δ18O L. littorea-salinity training set previously developed for the Limfjord, Denmark to quantify winter salinity. δ18O values range between +1.6% and +4.0% in the late Mesolithic and ‒6.3% to +2.0% in the early Neolithic. Using maximum δ18O values, winter salinity at the known temperature of growth cessation in L. littorea (i.e. +3.7 ± 1°C) for the first annual cycle of each shell ranges between 25.5 and 26.8 psu (standard deviation (SD): 0.56) for the late Mesolithic, with an average salinity of 26.1 psu. Early-Neolithic shells range between 19.4 and 28.2 psu (SD: 4.59) with an average salinity of 23.7 psu. No statistically significant change in salinity occurs between the late Mesolithic and early Neolithic. This result supports recent diatom/mollusc-based inferences that salinity was not the sole cause of the oyster decline, although some evidence is presented here for more variable seasonal salinity conditions in the early Neolithic, which (along sedimentary change and temperature deterioration) might have increased stress on oyster populations in some years. It is recommended here that for robust palaeoenvironmental inferences, where possible, multiple specimens should be used from the same time period in conjunction with multiproxy data

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

The Transcription Factor GLI1 Mediates TGFb1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism

The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-b1 (TGFb1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGFb1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC.National Institutes of Health Grants CA100882 and CA128633 (to LRR) and CA165076; the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567) (to MEFZ); the Mayo Clinic Cancer Center (CA15083), the Mayo Clinic Center for Translational Science Activities (NIH/NCRR CTSA Grant Number KL2 RR024151), and an American Gastroenterological Association Foundation for Digestive Health and Nutrition Bridging Grant (to LRR)