Same brain, different look? The impact of scanner, sequence and preprocessing on diffusion imaging outcome parameters

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from, e.g., diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19–54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyrafit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps, obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability

Social isolation is linked to declining grey matter structure and cognitive functions in the LIFE-Adult panel study

Social isolation has been suggested to increase the risk to develop cognitive decline. However, our knowledge on causality and neurobiological underpinnings is still limited. In this preregistered analysis, we tested the impact of social isolation on central features of brain and cognitive aging using a longitudinal population-based magnetic resonance imaging (MRI) study. Assaying 1335 cognitively healthy participants (50-80 years old, 659 women) at baseline and 895 participants after ∼6 years follow-up, we found baseline social isolation and change in social isolation to be associated with smaller volumes of the hippocampus, reduced cortical thickness and poorer cognitive functions. Combining advanced neuroimaging outcomes with prevalent lifestyle characteristics from a well-characterized population of middle- to older aged adults, we provide evidence that social isolation contributes to human brain atrophy and cognitive decline. Within-subject effects of social isolation were similar to between-subject effects, indicating an opportunity to reduce dementia risk by promoting social networks

What builds resilience? Sociodemographic and social correlates in the population-based LIFE-adult-study

Resilience is closely related to mental health and well-being. Identifying risk groups with lower resilience and the variables associated with resilience informs preventive approaches. Previous research on resilience patterns in the general population is heterogeneous, and comprehensive large-scale studies are needed. The aim of our study is to examine sociodemographic and social correlates of resilience in a large population-based sample. We examined 4795 participants from the LIFE-Adult-Study. Assessments included resilience (RS-11), social support (ESSI), and social network (LSNS), as well as the sociodemographic variables age, gender, marital status, education, and occupation. The association of resilience with sociodemographic and social correlates was examined using linear regression analyses. Higher resilience was associated with female gender, married marital status, high education, and full-time occupation. Social support and social network were positively associated with resilience. Our results implicate that resilience is related to various sociodemographic variables. Social variables seem to be particularly important for resilience. We identified risk groups with lower resilience, which should be given special attention by public health policies, especially in times of crisis. Reducing loneliness and promoting social connectedness may be promising ways to build resilience in the general population

Reading cognition from the eyes: Association of retinal nerve fiber layer thickness with cognitive performance in a population-based study

With the eye as a window to the brain, non-invasive fast screening of retinal nerve fibre layer thickness poses the opportunity for early detection of cognitive decline leading to dementia. Our objective is to determine whether performance in various neurocognitive tests has an association with itemized retinal nerve fibre layer thickness. Detailed investigation of associations factored in sex and eye-side. The large population-based LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was conducted at Leipzig University, Germany from 2011 to 2014. Randomly selected participants (N = 10 000) were drawn from population registry in an age- and gender-stratified manner, focusing on 40-80 years. Cognitive function was examined with the CERAD-NP Plus test-battery (Consortium to Establish a Registry for Alzheimer's Disease), Stroop-Test, Reading the Mind in the Eyes-Test and Multiple-Choice Vocabulary Intelligence Test. Circumpapillary retinal nerve fibre layer thickness was measured with Optical Coherence Tomography. Subjects with reliable measurements (≥50 B-scan repetitions, signal-to-noise-ratio ≥20 dB, ≤5% missing A-scans) and without clinical eye pathology (sample A) and additional exclusion due to conditions of the central nervous system (sample B) were evaluated. The relationship between cognitive function and retinal nerve fibre layer thickness was investigated for six segments: temporal, temporal-superior, temporal-inferior, nasal, nasal-superior and nasal-inferior. For comparison with other studies, global mean is given. Brain-side projection analysis links results to the corresponding brain hemisphere. We analysed 11 124 eyes of 6471 subjects [55.5 years of age (19.1-79.8 years), 46.9% male]. Low cognitive performance was predominantly associated with thinner retinal nerve fibre layer thickness. Correlation analysis indicated emphasis on global and temporally located effects. Multivariable regression analysis with adjustments (age, sex and scan radius) presented individual results for each test, differentiating between sex and eye-side. For instance, verbal fluency tests and Trail Making Test-B show stronger association in females; Trail Making Test-A shows right-eye dominance. Findings in Trail-Making-Test-A projected to left brain hemisphere, and the ratio incongruent to neutral in the Stroop test projected to right brain-hemisphere. Separate assessment for sex and eye-side is presented for the first time in a population-based study. Location-specific sectorial retinal nerve fibre layer thickness was found to be an indicator for cognitive performance, giving an option for early detection of cognitive decline and the potential of early treatment. The eye as a window to the brain was studied with optical coherence tomography and connected to cognition. Girbardt et al. report that thinner retinal nerve fibre layer thickness was found to be a meaningful index for poorer cognitive performance which presents the potential for prediction of future cognitive decline

Anxiety and food addiction in men and women: Results from the longitudinal LIFE-adult-study

Background: Anxiety is a widespread phenomenon, and it is connected to disordered eating and obesity. We want to analyze the connection between anxiety and food addiction (FA) over two points in time to better understand the directionality of the association. Since there are gender differences with regard to anxiety and eating, we are also interested in differences between men and women. Methods: We used data from the population-based LIFE-Adult-Study (N = 1,474) at time 1 (baseline) and time 2 (first follow-up) to analyze the connections between anxiety (GAD-7) and FA (YFAS) using a multiple group latent cross-lagged panel model with female and male participants as groups. We controlled for age, marital status, socioeconomic status and social support. Results: Anxiety (women: β = 0.50, p ≤ 0.001; men: β = 0.59, p ≤ 0.001) as well as FA (women: β = 0.37, p ≤ 0.001; men: β = 0.58, p ≤ 0.001) exhibited stability over time for both genders. We found a significant association between anxiety at time 1 and FA at time 2 for women (β = 0.25, p ≤ 0.001) but not for men (β = 0.04, p = 0.10), and significant associations between FA at time 1 and anxiety at time 2 for women (β = 0.23, p ≤ 0.001) as well as men (β = 0.21, p ≤ 0.001). Conclusion: Food addiction longitudinally affects anxiety, independent of gender and other sociodemographic variables. In addition, anxiety affects subsequent FA as well, but only in women. Interventions that address FA could reduce anxiety in men and women, while interventions that mitigate anxiety could help prevent FA in women

Photopatterned antibodies for selective cell attachment

We present a phototriggerable system that allows for the spatiotemporal controlled attachment of selected cell types to a biomaterial using immobilized antibodies that specifically target individual cell phenotypes.o-Nitrobenzyl caged biotin was used to functionalize chitosan membranes and mediate site-specific coupling of streptavidin and biotinylated antibodies after light activation. The ability of this system to capture and immobilize specific cells on a surface was tested using endothelial-specific biotinylated antibodies and nonspecific ones as controls. Homogeneous patterned monolayers of human umbilical vein endothelial cells were obtained on CD31-functionalized surfaces. This is a simple and generic approach that is applicable to other ligands, materials, and cell types and shows the flexibility of caged ligands to trigger and control the interaction between cells and biomaterials.We thank Martina Knecht (MPIP) for help with the synthesis of caged biotin and Dr. Ron Unger and Prof. C. J. Kirkpatrick (University Clinic Mainz, RepairLab) for providing HUVECs. C.A.C. acknowledges funding support from the Portuguese Foundation for Science and Technology (FCT) (fellowship SFRH/BD/61390/2009) and from the International Max-Planck Research School in Mainz. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. REGPOT-CT2012-316331-POLARIS

Functional Polymorphism of the CK2α Intronless Gene Plays Oncogenic Roles in Lung Cancer

Protein kinase CK2 is frequently up-regulated in human cancers, although the mechanism of CK2 activation in cancer remains unknown. In this study, we investigated the role of the CK2α intronless gene (CSNK2A1P, a presumed CK2α pseudogene) in the pathogenesis of human cancers. We found evidence of amplification and over-expression of the CSNK2A1P gene in non- small cell lung cancer and leukemia cell lines and 25% of the lung cancer tissues studied. The mRNA expression levels correlated with the copy numbers of the CSNK2A1P gene. We also identified a novel polymorphic variant (398T/C, I133T) of the CSNK2A1P gene and showed that the 398T allele is selectively amplified over the 398C allele in 101 non-small cell lung cancer tissue samples compared to those in 48 normal controls (p = 0.013<0.05). We show for the first time CSNK2A1P protein expression in transfected human embryonic kidney 293T and mouse embryonic fibroblast NIH-3T3 cell lines. Both alleles are transforming in these cell lines, and the 398T allele appears to be more transforming than the 398C allele. Moreover, the 398T allele degrades PML tumor suppressor protein more efficiently than the 398C allele and shows a relatively stronger binding to PML. Knockdown of the CSNK2A1P gene expression with specific siRNA increased the PML protein level in lung cancer cells. We report, for the first time, that the CSNK2A1P gene is a functional proto-oncogene in human cancers and its functional polymorphism appears to degrade PML differentially in cancer cells. These results are consistent with an important role for the 398T allele of the CSNK2A1P in human lung cancer susceptibility

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

Cerebellar astrocytes co-express several ADP receptors. Presence of functional P2Y13-like receptors

Astrocytes exhibit a form of excitability based on variations of intracellular Ca2+ concentration in response to various stimuli, including ADP, ATP, UTP and dinucleotides. Here, we investigate the presence of the recently cloned ADP-sensitive receptors, P2Y12 and P2Y13 subtypes, which are negatively coupled to adenylate cyclase, in cerebellar astrocytes. We checked the effect of specific agonists, 2-methylthioadenosine diphosphate (2MeSADP) and ADP, on adenylate cyclase stimulation induced by isoproterenol. Both agonists significantly reduced the cAMP accumulation induced by isoproterenol. The inhibitory effect was concentration-dependent with IC50 values of 46 ± 13 and 23 ± 14 nM for 2MeSADP and ADP, respectively. The experiments were carried out in the presence of MRS-2179, a specific antagonist of P2Y1 receptor, to avoid any contribution of this receptor. Using fura-2 microfluorimetry we also proved that astrocytes responded to 2MeSADP stimulations with calcium responses in the absence and also in the presence of MRS-2179. Both effects, inhibition of adenylate cyclase and intracellular calcium mobilization, were not modified by 2MeSAMP, an antagonist of P2Y12 receptor, suggesting that were mediated by P2Y13-like receptors

Association of Systemic Medication Use with Glaucoma and Intraocular Pressure:The European Eye Epidemiology Consortium

Purpose: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Design: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. Participants: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. Methods: We examined associations of 4 categories of systemic medications—antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications—with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. Main Outcome Measures: Glaucoma prevalence and IOP. Results: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, −0.33 mmHg; 95% CI, −0.57 to −0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, −0.45 mmHg; 95% CI −0.74 to −0.16 mmHg) and nonselective systemic β-blockers (β coefficient, −0.54 mmHg; 95% CI, −0.94 to −0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, −0.30 mmHg; 95% CI, −0.47 to −0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. Conclusions: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p