Cross Sectional Associations between Socio-Demographic Factors and Cognitive Performance in an Older British Population: The European Investigation of Cancer in Norfolk (EPIC-Norfolk) Study

$\textbf{BACKGROUND}$: Cognition covers a range of abilities, such as memory, response time and language, with tests assessing either specific or generic aspects. However differences between measures may be observed within the same individuals. $\textbf{OBJECTIVE}$: To investigate the cross-sectional association of cognitive performance and socio-demographic factors using different assessment tools across a range of abilities in a British cohort study. $\textbf{METHODS}$: Participants of the European Prospective Investigation of Cancer (EPIC) in Norfolk Study, aged 48-92 years, underwent a cognitive assessment between 2006 and 2011 (piloted between 2004 and 2006) and were investigated over a different domains using a range of cognitive tests. $\textbf{RESULTS}$: Cognitive measures were available on 8584 men and women. Though age, sex, education and social class were all independently associated with cognitive performance in multivariable analysis, different associations were observed for different cognitive tests. Increasing age was associated with increased risk of a poor performance score in all of the tests, except for the National Adult Reading Test (NART), an assessment of crystallized intelligence. Compared to women, men were more likely to have had poor performance for verbal episodic memory, Odds Ratio, OR = 1.99 (95% Confidence Interval, 95% CI 1.72, 2.31), attention OR = 1.62, (95% CI 1.39, 1.88) and prospective memory OR = 1.46, (95% CI 1.29, 1.64); however, no sex difference was observed for global cognition, OR = 1.07 (95%CI 0.93, 1.24). The association with education was strongest for NART, and weakest for processing speed. $\textbf{CONCLUSION}$: Age, sex, education and social class were all independently associated with performance on cognitive tests assessing a range of different domains. However, the magnitude of associations of these factors with different cognitive tests differed. The varying relationships seen across different tests may help explain discrepancies in results reported in the current literature, and provides insights into influences on cognitive performance in later life.The infrastructure for this study was supported by the Medical Research Council, UK http://www.mrc.ac.uk/ (Ref: G0401527) and Cancer Research UK http://www.cancerresearchuk.org/ (CRUK, Ref: C864/A8257). The clinic for EPIC-Norfolk 3 was funded by Research into Ageing, now known as Age UK http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/A2883). KK received the above funding. FEM Is supported by MRC (Ref: U105292687)

Cross Sectional Associations between Socio-Demographic Factors and Cognitive Performance in an Older British Population: The European Investigation of Cancer in Norfolk (EPIC-Norfolk) Study.

BACKGROUND: Cognition covers a range of abilities, such as memory, response time and language, with tests assessing either specific or generic aspects. However differences between measures may be observed within the same individuals. OBJECTIVE: To investigate the cross-sectional association of cognitive performance and socio-demographic factors using different assessment tools across a range of abilities in a British cohort study. METHODS: Participants of the European Prospective Investigation of Cancer (EPIC) in Norfolk Study, aged 48-92 years, underwent a cognitive assessment between 2006 and 2011 (piloted between 2004 and 2006) and were investigated over a different domains using a range of cognitive tests. RESULTS: Cognitive measures were available on 8584 men and women. Though age, sex, education and social class were all independently associated with cognitive performance in multivariable analysis, different associations were observed for different cognitive tests. Increasing age was associated with increased risk of a poor performance score in all of the tests, except for the National Adult Reading Test (NART), an assessment of crystallized intelligence. Compared to women, men were more likely to have had poor performance for verbal episodic memory, Odds Ratio, OR = 1.99 (95% Confidence Interval, 95% CI 1.72, 2.31), attention OR = 1.62, (95% CI 1.39, 1.88) and prospective memory OR = 1.46, (95% CI 1.29, 1.64); however, no sex difference was observed for global cognition, OR = 1.07 (95%CI 0.93, 1.24). The association with education was strongest for NART, and weakest for processing speed. CONCLUSION: Age, sex, education and social class were all independently associated with performance on cognitive tests assessing a range of different domains. However, the magnitude of associations of these factors with different cognitive tests differed. The varying relationships seen across different tests may help explain discrepancies in results reported in the current literature, and provides insights into influences on cognitive performance in later life.The infrastructure for this study was supported by the Medical Research Council, UK http://www.mrc.ac.uk/ (Ref: G0401527) and Cancer Research UK http://www.cancerresearchuk.org/ (CRUK, Ref: C864/A8257). The clinic for EPIC-Norfolk 3 was funded by Research into Ageing, now known as Age UK http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/A2883). KK received the above funding. FEM Is supported by MRC (Ref: U105292687)

Binary systems and their nuclear explosions

Peer ReviewedPreprin

Biophysical mechanisms of single-cell interactions with microtopographical cues

Biophysical cues encoded in the extracellular matrix (ECM) are increasingly being explored to control cell behavior in tissue engineering applications. Recently, we showed that cell adhesion to microtopographical structures (“micropegs”) can suppress proliferation in a manner that may be blunted by inhibiting cellular contractility, suggesting that this effect is related to altered cell-scaffold mechanotransduction. We now directly investigate this possibility at the microscale through a combination of live-cell imaging, single-cell mechanics methods, and analysis of gene expression. Using time-lapse imaging, we show that when cells break adhesive contacts with micropegs, they form F-actin-filled tethers that extend and then rupture at a maximum, critical length that is greater than trailing-edge tethers observed on topographically flat substrates. This critical tether length depends on myosin activation, with inhibition of Rho-associated kinase abolishing topography-dependent differences in tether length. Using cellular de-adhesion and atomic force microscopy indentation measurements, we show that the micropegs enhance cell-scaffold adhesive interactions without changing whole-cell elasticity. Moreover, micropeg adhesion increases expression of specific mechanotransductive genes, including RhoA GTPase and myosin heavy chain II, and, in myoblasts, the functional marker connexin 43. Together, our data support a model in which microtopographical cues alter the local mechanical microenvironment of cells by modulating adhesion and adhesion-dependent mechanotransductive signaling

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

What can health inequalities researchers learn from an intersectionality perspective?:Understanding social dynamics with an inter-categorical approach

The concept of intersectionality was developed by social scientists seeking to analyse the multiple interacting influences of social location, identity and historical oppression. Despite broad take-up elsewhere, its application in public health remains underdeveloped. We consider how health inequalities research in the United Kingdom has predominantly taken class and later socioeconomic position as its key axis in a manner that tends to overlook other crucial dimensions. We especially focus on international research on ethnicity, gender and caste to argue that an intersectional perspective is relevant for health inequalities research because it compels researchers to move beyond (but not ignore) class and socioeconomic position in analysing the structural determinants of health. Drawing on these theoretical developments, we argue for an inter-categorical conceptualisation of social location that recognises differentiation without reifying social groupings – thus encouraging researchers to focus on social dynamics rather than social categories, recognising that experiences of advantage and disadvantage reflect the exercise of power across social institutions. Such an understanding may help address the historic tendency of health inequalities research to privilege methodological issues and consider different axes of inequality in isolation from one another, encouraging researchers to move beyond micro-level behaviours to consider the structural drivers of inequalities

Increased Abundance of M cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility

Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases

Diversity of Hepatitis B genotypes in Nepal and updated Phylogenetic Tree: a Pilot Survey in 2012

Introduction: Hepatitis B virus is a current global health problem. HBV genotypes influence the treatment and long term outcome of HBV infected patients. Moreover, HBV genotypes differ in various region of the world. Such data was reported haphazardly but yet to be comprehensive for Nepal. This study attempted to find out the diverse hepatitis B genotypes in Nepal. Methods: A convenient serum sample of 58 HBsAg positive patients from different parts of the country mainly from Nepalgunj, Palpa and Kathmandu were screened for hepatitis B genotype. Sequencing was done and Phylogenetic tree was created. Results: Among 58 samples, 23 were genotype D, 17were genotype A and B wereC/D recombinant. Phylogenetic trees were created by distance-matrix and neighbor-joining analyses after bootstrapping to 1000 replicates. Discussion: HBV genotypes A and D are the most common genotype in Nepal. Horizontal transmission is common in these genotypes. C/D recombinant genotype may be transmitted from Tibetan people living in Kathmandu. Prophylactic major controlling, horizontal and cross border transmission could be effective. Conclusions: Three major genotypes of HBV in Nepal were found to be A, C and D. Despite being a low prevalence area, Nepal has a diversity of hepatitis B genotypes.  Keywords: genotypes; HBV; nepal