Synthesis of 3-Functionalized 4-Quinolones from Readily Available Anthranilic Acids.

We report herein an efficient synthesis of 3-functionalized 4-quinolones, a class of privileged pharmacophores found in numerous biologically and pharmaceutically active compounds. Our synthetic strategy features a telescoped two-step sequence starting from readily available anthranilic acids and functionalized methane derivatives bearing an electron-withdrawing group, such as methyl sulfones, methyl ketones, and acetonitrile. The method delivers good to excellent yields for a variety of structurally diverse substrates, showing good functional group tolerability. We believe that the disclosed method offers a highly efficient and practical entry to functionalized 4-quinolones under mild conditions that is amenable to preparative-scale synthesis.

Deep learning algorithms to detect diabetic kidney disease from retinal photographs in multiethnic populations with diabetes.

OBJECTIVE: To develop a deep learning algorithm (DLA) to detect diabetic kideny disease (DKD) from retinal photographs of patients with diabetes, and evaluate performance in multiethnic populations. MATERIALS AND METHODS: We trained 3 models: (1) image-only; (2) risk factor (RF)-only multivariable logistic regression (LR) model adjusted for age, sex, ethnicity, diabetes duration, HbA1c, systolic blood pressure; (3) hybrid multivariable LR model combining RF data and standardized z-scores from image-only model. Data from Singapore Integrated Diabetic Retinopathy Program (SiDRP) were used to develop (6066 participants with diabetes, primary-care-based) and internally validate (5-fold cross-validation) the models. External testing on 2 independent datasets: (1) Singapore Epidemiology of Eye Diseases (SEED) study (1885 participants with diabetes, population-based); (2) Singapore Macroangiopathy and Microvascular Reactivity in Type 2 Diabetes (SMART2D) (439 participants with diabetes, cross-sectional) in Singapore. Supplementary external testing on 2 Caucasian cohorts: (3) Australian Eye and Heart Study (AHES) (460 participants with diabetes, cross-sectional) and (4) Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) (265 participants with diabetes, cross-sectional). RESULTS: In SiDRP validation, area under the curve (AUC) was 0.826(95% CI 0.818-0.833) for image-only, 0.847(0.840-0.854) for RF-only, and 0.866(0.859-0.872) for hybrid. Estimates with SEED were 0.764(0.743-0.785) for image-only, 0.802(0.783-0.822) for RF-only, and 0.828(0.810-0.846) for hybrid. In SMART2D, AUC was 0.726(0.686-0.765) for image-only, 0.701(0.660-0.741) in RF-only, 0.761(0.724-0.797) for hybrid. DISCUSSION AND CONCLUSION: There is potential for DLA using retinal images as a screening adjunct for DKD among individuals with diabetes. This can value-add to existing DLA systems which diagnose diabetic retinopathy from retinal images, facilitating primary screening for DKD.

Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): health assessment protocol, participant profile and patterns of participation.

BACKGROUND: The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) is a prospective, longitudinal study of a representative cohort of older adults living in Northern Ireland, United Kingdom. Its aim is to explore the social, behavioural, economic and biological factors of ageing and how these factors change as people age. The study has been designed to maximize comparability with other international studies of ageing thereby facilitating cross-country comparisons. This paper provides an overview of the design and methodology of the health assessment which was carried out as part of Wave 1. METHODS: Three thousand, six hundred and fifty five community dwelling adults, aged 50 years and over participated in the health assessment as part of Wave 1 of NICOLA. The health assessment included a battery of measurements across various domains that addressed key indicators of ageing namely: physical function, vision and hearing, cognitive function, and cardiovascular health. This manuscript describes the scientific rationale for the choice of assessments, provides an overview of the core objective measures carried out in the health assessment and describes the differences in characteristics of participants who took part in the health assessment compared to those who did not take part. RESULTS: The manuscript highlights the importance of incorporating objective measures of health in population based studies as a means of complementing subjective measures and as a way to advance our understanding of the ageing process. The findings contextualize NICOLA as a data resource within Dementias Platform UK (DPUK), the Gateway to Global Ageing (G2G) and other existing networks of population based longitudinal studies of ageing. CONCLUSION: This manuscript can help inform design considerations for other population based studies of ageing and facilitate cross-country comparative analysis of key life-course factors affecting healthy ageing such as educational attainment, diet, the accumulation of chronic conditions (including Alzheimer's disease, dementia and cardiovascular disease) as well as welfare and retirement policies.

A peer support dietary change intervention for encouraging adoption and maintenance of the Mediterranean diet in a non-Mediterranean population (TEAM-MED): lessons learned and suggested improvements.

Peer support interventions for dietary change may offer cost-effective alternatives to interventions led by health professionals. This process evaluation of a trial to encourage the adoption and maintenance of a Mediterranean diet in a Northern European population at high CVD risk (TEAM-MED) aimed to investigate the feasibility of implementing a group-based peer support intervention for dietary change, positive elements of the intervention and aspects that could be improved. Data on training and support for the peer supporters; intervention fidelity and acceptability; acceptability of data collection processes for the trial and reasons for withdrawal from the trial were considered. Data were collected from observations, questionnaires and interviews, with both peer supporters and trial participants. Peer supporters were recruited and trained to result in successful implementation of the intervention; all intended sessions were run, with the majority of elements included. Peer supporters were complimentary of the training, and positive comments from participants centred around the peer supporters, the intervention materials and the supportive nature of the group sessions. Attendance at the group sessions, however, waned over the intervention, with suggested effects on intervention engagement, enthusiasm and group cohesion. Reduced attendance was reportedly a result of meeting (in)frequency and organisational concerns, but increased social activities and group-based activities may also increase engagement, group cohesion and attendance. The peer support intervention was successfully implemented and tested, but improvements can be suggested and may enhance the successful nature of these types of interventions. Some consideration of personal preferences may also improve outcomes.

Overcoming challenges regarding reference materials and regulations that influence global standardization of medical laboratory testing results.

BACKGROUND: Standardized results for laboratory tests are particularly important when their interpretation depends on fixed medical practice guidelines or common reference intervals. The medical laboratory community has developed a roadmap for an infrastructure to achieve standardized test results described in the International Organization for Standardization standard 17511:2020 In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples. Among the challenges to implementing metrological traceability are the availability of fit-for-purpose matrix-based certified reference materials (CRMs) and requirements for regulatory review that differ among countries. A workshop in December 2021 focused on these two challenges and developed recommendations for improved practices. DISCUSSION: The participants agreed that prioritization of measurands for standardization should be based on their impact on medical decisions in a clinical pathway. Ensuring that matrix-based CRMs are globally available for more measurands will enable fit-for-purpose calibration hierarchies for more laboratory tests. Regulation of laboratory tests is important to ensure safety and effectiveness for the populations served. Because regulations are country or region specific, manufacturers must submit recalibration changes intended to standardize results for regulatory review to all areas in which a measuring system is marketed. RECOMMENDATIONS: A standardization initiative requires collaboration and planning among all interested stakeholders. Global collaboration should be further developed for prioritization of measurands for standardization, and for coordinating the production and supply of CRMs worldwide. More uniform regulatory submission requirements are desirable when recalibration is implemented to achieve internationally standardized results.

Prevalence and risk factors for age-related macular degeneration in a population-based cohort study of older adults in Northern Ireland using multimodal imaging: NICOLA Study.

PURPOSE: To report prevalence and risk factor associations for age-related macular degeneration (AMD) and AMD features from multimodal retinal grading in a multidisciplinary longitudinal population-based study of aging in Northern Ireland. STUDY DESIGN: Population-based longitudinal cohort study. METHODS: Retinal imaging at the Norther Ireland Cohort for the Longitudinal Aging Study health assessment included stereo Colour Fundus Photography (CFP) (Canon CX-1, Tokyo, Japan) and Spectral-Domain Optical Coherence Tomography (SD-OCT) ((Heidelberg Retinal Angopgraph (HRA)+OCT; Heidelberg Engineering, Heidelberg, Germany). Medical history and demographic information was obtained during a home interview. Descriptive statistics were used to describe the prevalence of AMD and individual AMD features. Multiple imputation followed by multiple regression modelling was used to explore risk factor associations including relationships with AMD genetic risk score. RESULTS: Retinal images from 3386 participants were available for analysis. Mean age of the sample was 63.4 (SD 9.01, range: 36-99). Population weighted prevalence of AMD using colour grading in those over 55 years was: no drusen: 6 0.4%; drusen <63 µm: 15.9%; drusen 63-125 µm: 13.7%; drusen >125 µm or pigmentary changes: 8.3%; late AMD: 1.6%. Prevalence of AMD features in those over 55 years was: OCT drusen 27.5%, complete outer retinal pigment epithelium and outer retinal atrophy (cRORA) on OCT was 4.3%, reticular drusen 3.2% and subretinal drusenoid deposits 25.7%. The genetic risk score was significantly associated with drusen and cRORA but less so for SDD alone and non-significant for hyperpigmentation or vitelliform lesions. CONCLUSIONS: Multimodal imaging-based classification has provided evidence of some divergence of genetic risk associations between classical drusen and SDD. Our findings support an urgent review of current AMD severity classification systems.

A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events.

BACKGROUND: Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the 'next-generation' epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2. RESULTS: Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant). CONCLUSIONS: We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures.

Culturally adapting the Mediterranean Diet pattern - a way of promoting more 'sustainable' dietary change?

Average diet quality is low in the UK and is socioeconomically patterned, contributing to the risk of non-communicable disease and poor health. Achieving meaningful dietary change in the long term is challenging, with intervention required on a number of different levels which reflect the multiple determinants of dietary choice. Dietary patterns have been identified which contribute positively to health outcomes; one of these is the Mediterranean diet (MD) which has been demonstrated to be associated with reduced non-communicable disease risk. Most research exploring the health benefits of the MD has been conducted in Mediterranean regions but, increasingly, research is also being conducted in non-Mediterranean regions. The MD is a dietary pattern that could have positive impacts on both health and environmental outcomes, while being palatable, appetising and acceptable. In this review, we consider the studies that have explored transferability of the MD. To achieve long-term dietary change towards a MD, it is likely that the dietary pattern will have to be culturally adapted, yet preserving the core health-promoting elements and nutritional composition, while considering the food system transition required to support changes at population level. Population-specific barriers need to be identified and ways sought to overcome these barriers, for example, key food availability and cost. This should follow a formal cultural adaptation framework. Such an approach is likely to enhance the extent of adherence in the longer term, thus having an impact on population health.

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Lower carbohydrate diets for adults with type 2 diabetes.

In May 2021, the Scientific Advisory Committee on Nutrition (SACN) published a risk assessment on lower carbohydrate diets for adults with type 2 diabetes (T2D)(). The purpose of the report was to review the evidence on 'low'-carbohydrate diets compared with the current UK government advice on carbohydrate intake for adults with T2D. However, since there is no agreed and widely utilised definition of a 'low'-carbohydrate diet, comparisons in the report were between lower and higher carbohydrate diets. SACN's remit is to assess the risks and benefits of nutrients, dietary patterns, food or food components for health by evaluating scientific evidence and to make dietary recommendations for the UK based on its assessment(). SACN has a public health focus and only considers evidence in healthy populations unless specifically requested to do otherwise. Since the Committee does not usually make recommendations relating to clinical conditions, a joint working group (WG) was established in 2017 to consider this issue. The WG comprised members of SACN and members nominated by Diabetes UK, the British Dietetic Association, Royal College of Physicians and Royal College of General Practitioners. Representatives from NHS England and NHS Health Improvement, the National Institute for Health and Care Excellence and devolved health departments were also invited to observe the WG. The WG was jointly chaired by SACN and Diabetes UK.

The feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet in established community groups at increased CVD risk: the TEAM-MED EXTEND study: a pilot cluster randomised controlled trial.

This study aimed to evaluate the feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet (MD) in established community groups where existing social support may assist the behaviour change process. Four established community groups with members at increased Cardiovascular Disease (CVD) risk and homogenous in gender were recruited and randomised to receive either a 12-month Peer Support (PS) intervention (PSG) (n 2) or a Minimal Support intervention (educational materials only) (MSG) (n 2). The feasibility of the intervention was assessed using recruitment and retention rates, assessing the variability of outcome measures (primary outcome: adoption of an MD at 6 months (using a Mediterranean Diet Score (MDS)) and process evaluation measures including qualitative interviews. Recruitment rates for community groups (n 4/8), participants (n 31/51) and peer supporters (n 6/14) were 50 %, 61 % and 43 %, respectively. The recruitment strategy faced several challenges with recruitment and retention of participants, leading to a smaller sample than intended. At 12 months, a 65 % and 76·5 % retention rate for PSG and MSG participants was observed, respectively. A > 2-point increase in MDS was observed in both the PSG and the MSG at 6 months, maintained at 12 months. An increase in MD adherence was evident in both groups during follow-up; however, the challenges faced in recruitment and retention suggest a definitive study of the peer support intervention using current methods is not feasible and refinement based on the current feasibility study should be incorporated. Lessons learned during the implementation of this intervention will help inform future interventions in this area.

Trial to Encourage Adoption and Maintenance of a MEditerranean Diet (TEAM-MED): a randomised pilot trial of a peer support intervention for dietary behaviour change in adults from a Northern European population at high CVD risk.

Adhering to a Mediterranean diet (MD) is associated with reduced CVD risk. This study aimed to explore methods of increasing MD adoption in a non-Mediterranean population at high risk of CVD, including assessing the feasibility of a developed peer support intervention. The Trial to Encourage Adoption and Maintenance of a MEditerranean Diet was a 12-month pilot parallel group RCT involving individuals aged ≥ 40 year, with low MD adherence, who were overweight, and had an estimated CVD risk ≥ 20 % over ten years. It explored three interventions, a peer support group, a dietician-led support group and a minimal support group to encourage dietary behaviour change and monitored variability in Mediterranean Diet Score (MDS) over time and between the intervention groups, alongside measurement of markers of nutritional status and cardiovascular risk. 118 individuals were assessed for eligibility, and 75 (64 %) were eligible. After 12 months, there was a retention rate of 69 % (peer support group 59 %; DSG 88 %; MSG 63 %). For all participants, increases in MDS were observed over 12 months (P < 0·001), both in original MDS data and when imputed data were used. Improvements in BMI, HbA1c levels, systolic and diastolic blood pressure in the population as a whole. This pilot study has demonstrated that a non-Mediterranean adult population at high CVD risk can make dietary behaviour change over a 12-month period towards an MD. The study also highlights the feasibility of a peer support intervention to encourage MD behaviour change amongst this population group and will inform a definitive trial.

Implementation of the new EU IVD regulation - urgent initiatives are needed to avert impending crisis.

Laboratory medicine in the European Union is at the dawn of a regulatory revolution as it reaches the end of the transition from IVDD 98/79/EC (https://eur-lex.eur-opa.eu/legal-content/EN/TXT/?uri=CELEX%3A31998L0079&qid=1628781352814) to IVDR 2017/746 https://eur-lex.europa.eu/eli/reg/2017/746. Without amendments and contingency plans, implementation of the IVDR in May 2022 will lead the healthcare sector into uncharted waters due to unpreparedness of the EU regulatory infrastructure. Prospective risk analyses were not made by the European Commission, and if nothing happens it can be anticipated that the consequences will impact all stakeholders of the medical test pipeline, may seriously harm patients and may prevent caregivers from making appropriate clinical decisions due to non-availability of medical tests. Finally, it also may discourage manufacturers and academia from developing specialty tests, thereby hampering innovation in medical diagnostic care. We hereby inform laboratory professionals about the imminent diagnostic collapse using testimonies from representative stakeholders of the diagnostic supply chain and from academia developing innovative in-house tests in domains of unmet clinical needs. Steps taken by the EFLM Task Force on European Regulatory Affairs, under the umbrella of the Biomedical Alliance in Europe, will be highlighted, as well as the search for solutions through dialogue with the European Commission. Although we recognize that the IVDR promotes positive goals such as increased clinical evidence, surveillance, and transparency, we need to ensure that the capabilities of the diagnostic sector are not damaged by infrastructural unpreparedness, while at the same time being forced to submit to a growing bureaucratic and unsupportive structure that will not support its "droit d'exister".

FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis.

Association of renal impairment with cognitive dysfunction in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).

INTRODUCTION: Chronic kidney disease (CKD) is a recognized risk factor for cognitive impairment. Identification of those at greatest risk of cognitive impairment may facilitate earlier therapeutic intervention. This study evaluated associations between estimated glomerular filtration rate (eGFR) and cognitive function in the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: Data were available for 3412 participants ≥50 years of age living in non-institutionalized settings who attended a health assessment between February 2014 and March 2016. Measures of serum creatinine (SCr) and cystatin C (cys-C) were used for eGFR. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). RESULTS: Following adjustment for potential confounders, a single unit decrease in eGFR was significantly associated with reduced cognitive function defined by an MMSE ≤24/30 {eGFR calculated using serum cys-C [eGFRcys]: ß = -0.01 [95% confidence interval (CI) -0.001 to -0.01], P = 0.01} and MoCA <26/30 [ß = -0.01 (95% CI -0.002 to -0.02), P = 0.02]. Similarly, CKD Stages 3-5 were also associated with a moderate increase in the odds of cognitive impairment (MMSE ≤24) following adjustment for confounders [eGFRcys: odds ratio 2.73 (95% CI 1.38-5.42), P = 0.004]. CONCLUSIONS: Decreased eGFRcys was associated with a significantly increased risk of cognitive impairment in a population-based cohort of older adults. However, there was no evidence of an association between cognitive impairment and the more commonly used eGFR calculated using SCr. eGFRcys may offer improved sensitivity over eGFRcr in the determination of renal function and associated risk of cognitive impairment.

Dietary patterns associated with renal impairment in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).

BACKGROUND: Dietary-based primary prevention guidelines for chronic kidney disease (CKD) treatment are lacking due to limited evidence. Single nutrient intake studies do not account for complex dietary interactions. We assessed associations between dietary patterns and renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA). DESIGN: A cross-sectional observational study used NICOLA baseline dietary data collected between February 2014 and March 2016 via a food frequency questionnaire for 2590 participants aged ≥ 50 years. Principal component analysis identified a posteriori dietary patterns. Renal function was characterised by estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin-C. Associations were assessed according to quintiles of dietary pattern adherence and multivariable regression analysis examined associations with eGFR. RESULTS: Variation in three dietary patterns was significantly associated with eGFR. After adjustment for potential confounders, participants with least adherence to the 'healthy' dietary pattern 1 had a mean eGFR 3.4 ml/min/1.73m2 (95% confidence interval, [CI] - 5.0, - 1.7, p < 0.001) lower than the most adherent. Those with lowest adherence to the 'unhealthy' dietary pattern 2 had a mean eGFR 1.9 ml/min/1.73m2 (CI 0.2, 3.5, p = 0.03) higher than those with highest adherence. Participants with lowest adherence to dietary pattern 3, characterised by a high consumption of alcohol and coffee, had a mean eGFR 1.8 ml/min/1.73m2 (- 3.5, - 0.01, p = 0.05) lower than those with greatest adherence. CONCLUSIONS: Our findings identify independent associations between dietary patterns and eGFR. These findings can inform the development of diet-related primary prevention advice for CKD.

Evidence for Structural and Functional Damage of the Inner Retina in Diabetes With No Diabetic Retinopathy.

Purpose: To provide structural and functional evidence of inner retinal loss in diabetes prior to vascular changes and interpret the structure-function relationship in the context of an established neural model. Methods: Data from one eye of 505 participants (134 with diabetes and no clinically evident vascular alterations of the retina) were included in this analysis. The data were collected as part of a large population-based study. Functional tests included best-corrected visual acuity, Pelli-Robson contrast sensitivity, mesopic microperimetry, and frequency doubling technology perimetry (FDT). Macular optical coherence tomography volume scans were collected for all participants. To interpret the structure-function relationship in the context of a neural model, ganglion cell layer (GCL) thickness was converted to local ganglion cell (GC) counts. Results: The GCL and inner plexiform layer were significantly thinner in participants with diabetes (P < 0.05), with no significant differences in the macular retinal nerve fiber layer or the outer retina. All functional tests except microperimetry showed a significant loss in diabetic patients (P < 0.05). Both FDT and microperimetry showed a significant relationship with the GC count (P < 0.05), consistent with predictions from a neural model for partial summation conditions. However, the FDT captured additional significant damage (P = 0.03) unexplained by the structural loss. Conclusions: Functional and structural measurements support early neuronal loss in diabetes. The structure-function relationship follows the predictions from an established neural model. Functional tests could be improved to operate in total summation conditions in the macula, becoming more sensitive to early loss.