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Background and Aims: Chronic inflammation plays a key role in arterial stiffness pathogenesis. Dietary components can display anti- or pro-inflammatory properties. Nonetheless, the association between the diet's overall inflammatory potential and arterial stiffness is unclear. This study aimed to assess the association between the diet's overall inflammatory potential and arterial stiffness assessed by carotid-femoral pulse wave velocity (cfPWV)., Methods and Results: This cross-sectional study included 1307 participants from the STANISLAS family cohort study. Dietary data were collected using a validated food frequency questionnaire. The adapted dietary inflammatory index (ADII) score was calculated to assess the inflammatory potential of the participants' diet. The association of ADII score quartile with cfPWV was assessed using IPW-weighted linear mixed models with random family effect. The median (Q1-Q3) ADII score was 0.45 (-1.57, 2.04). Participants exhibiting higher ADII scores demonstrated elevated energy intake, dietary saturated fat, and ultra-processed foods. Conversely, individuals with lower ADII scores exhibited higher vitamins and omega intakes, and a higher diet quality, as assessed by the DASH score. Despite these observations from the descriptive analyses, ADII score quartiles were not significantly associated with cfPWV (β(95% CI) were 0.01 (-0.02,0.04) for Q2, 0.02 (-0.01,0.05) for Q3, and 0.02 (-0.01,0.05) for Q4 compared to Q1)., Conclusion: In this cross-sectional study, participants had a relatively modest consumption of pro-inflammatory foods, no substantial associations were observed between the diet inflammatory potential and arterial stiffness. Further longitudinal studies in larger cohorts are needed to better understand the link between inflammatory diet and arterial stiffness., Competing Interests: Declaration of competing interest NG received honoraria from AstraZeneca, Bayer, Boehringer, Echosens, Lilly, Roche diagnostics, Novartis. PR: reports consulting for Idorsia, G3P, honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, Cincor, CVRx, Fresenius, KBP biosciences, Novartis, NovoNordisk, Relypsa, Servier, and Vifor Fresenius Medical Care Renal Pharma; and travel grants from AstraZeneca, Bayer, CVRx, Novartis, and Vifor Fresenius Medical Care Renal Pharma; Cofounder: CardioRenal. The other co-authors have no conflicts of interest to disclose related to the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Environmental factors favoring myopia development are still being studied and there is accumulating evidence for a significant role of nearwork. Recently, reading standard black-on-white text was found to activate the retinal OFF pathway and induce choroidal thinning, which is associated with myopia onset. Contrarily, reading white-on-black text led to thicker choroids, being protective against myopia. Respective effects on retinal processing are yet unknown. Here, we exploratively assessed the impact of contrast polarity on the retinal activity and possible interactions with eccentricity and refractive error. We recorded pattern electroretinograms in myopic and emmetropic adults while presenting a dead leaves stimulus (DLS), overlaid by masks of different size in ring or circle shape, either filled with uniform gray or text of inverted or standard contrast. In myopes, retinal responses for DLS with standard and inverted contrast were larger when the perifovea was stimulated (6-12 deg), however, including the fovea resulted in smaller amplitudes for inverted contrast than in emmetropes. The retina of emmetropes was more sensitive to inverted contrast than to standard and gray within 12 deg, but most sensitive for gray in the perifovea. This demonstrates that the refractive error influences the sensitivity to text contrast polarity, with a special role of the peripheral retina, which is in line with previous studies about blur sensitivity. Defining whether the differences derive from retinal processing or anatomical features of a myopic eye requires further investigation. Our approach might be a first step to explain how nearwork promotes the eye's elongation., (© 2023. The Author(s).)

Transcorneal electrical stimulation (TES) is used as therapy for retinal diseases such as retinitis pigmentosa (RP) and was suggested for assessing retinal sensitivity by determining phosphene thresholds, subjective luminance impressions caused by retinal stimulation. Further applications concerned the accommodation process, revealing an improved accommodative amplitude in presbyopic eyes after TES treatment. The respective changes of the ciliary muscle (CM), the structure most important for near vision, during TES are yet unknown. In a pilot study, we aimed to assess whether monocular TES leads to morphological and functional CM changes and whether central accommodation control is affected. Ten healthy, near-emmetropic adults participated in the trial (4 females, age 26.3 ± 3.6 years). Using a wavefront and a stimulus generator, a biphasic square-wave stimulus (2 s positive and 6 s negative amplitude) of 0 μA average current was produced and transferred to the eye by means of a Dawson-Trick & Litzkow electrode. Prior to the stimulation, an individual determination of phosphene thresholds served to define individual TES current amplitudes, which ranged between 60 and 100 μA. Optical coherence tomography (OCT) imaging of the right eye's temporal ciliary muscle was performed before and during ipsi- as well as contralateral monocular TES in randomized order in the morning and afternoon of the same day. During imaging, subjects fixated a target at 4 m distance and refraction was simultaneously recorded via eccentric infrared photorefraction. OCT images were assessed using previously published custom-developed software, allowing the definition of selective CM thickness (CMT) readings, and plotting of continuous CMT profiles along the muscle border. CMT profiles revealed that both stimulations, on the ipsi- and contralateral eye, induced a thickening of the CM compared to the non-stimulated state. The selective CMT readings confirmed a significant increase with ipsi- (31 ± 30 μm; p = 0.010) and contralateral (25 ± 16 μm; p = 0.001) TES. However, refraction during far vision was not significantly affected by either stimulation (ipsilateral [n = 5]: median Δ w/-w/o  = 0 D; contralateral [n = 7]: Δ w/-w/o  = 0.13 D). Pupil size on average increased during TES, but without reaching significance (ipsilateral [n = 5] median Δ w/-w/o  = 0.23 mm, contralateral [n = 7] Δ w/-w/o  = 0.39 mm). Ipsilateral CM thickening could be explained by local changes within the stimulated ciliary muscle, such as increased blood flow or interstitial fluid rise induced by TES. However, the CMT increase in the right eye when TES was performed contralaterally, on the left eye, indicates an involvement of the central control circuit of accommodation. Further possible explanations for this finding are a synchronization of neuronal activities in the visual pathway, the release of vasoactive neuropeptides, or effects on the central blood pressure regulation. Given a neuromodulation effect on the CM function, TES might have implications for children with accommodation insufficiencies and as additional therapy in myopia control management, e.g. in combination with multifocal contact lens treatment. Our study is important for the clinical application of TES, and the outcome might add crucial knowledge to the current understanding of the accommodation process and inform research and treatment of both myopia and presbyopia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and renal damage (CVRD) or hypertension in adulthood. Our study investigated the association of birth weight with early CVRD markers as well as the heritability of birth weight in an initially healthy family-based cohort., Methods: This study was based on 1028 individuals from the familial longitudinal STANISLAS cohort (399 parents/629 children) initiated in 1993-1995, with a fourth examination conducted in 2011-2016. Analyses performed at the fourth visit included pulse-wave velocity, central pressure, ambulatory blood pressure, hypertension status, diastolic dysfunction/distensibility, left ventricular mass indexed (LVMI), carotid intima-media thickness and kidney damage. The family structure of the cohort allowed birth weight heritability estimation., Results: Mean (±SD) birth weight was 3.3 ± 0.6 kg. Heritability was moderate (42-44%). At the fourth visit, individuals were 37 years old (32.0-57.0), 56% were women and 13% had antihypertensive treatment. Birth weight was strongly and negatively associated with hypertension [odds ratio (OR) 95% confidence interval (CI) 0.61 (0.45-0.84)]. A nonlinear association was found with LVMI, participants with a birth weight greater than 3 kg having a higher LVMI. A positive association ( β 95% CI 5.09 (1.8-8.38)] was also observed between birth weight and distensibility for adults with normal BMI. No associations were found with other CVRD., Conclusion: In this middle-aged population, birth weight was strongly and negatively associated with hypertension, and positively associated with distensibility in adults with normal BMI and with LVMI for higher birth weights. No associations were found with other CVRD markers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking., Methods: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N  = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores., Results: A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity., Conclusion: In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Several dimensions of eating behaviour (EB), such as restrained eating (RE), appear to be cross-sectionally associated with certain cardiovascular (CV) diseases and metabolic risk factors although little is known regarding longitudinal associations. This study aimed to assess the associations between EB and CV damage or metabolic syndrome after 13 years, in initially healthy individuals., Methods and Results: This study included 1109 participants from the familial STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort study. Emotional eating (EmE), RE, and external eating were assessed using the Dutch Eating Behaviour Questionnaire. Metabolic syndrome and CV damages such as carotid-femoral pulse-wave velocity (cfPWV), left ventricular mass, carotid intima-media thickness, and diastolic dysfunction (DD) were measured after a period of 13 years. Mixed model analysis with a family random effect and adjustment for age, sex, education, temporal gap, physical activity, metabolic factors at baseline, and the onset of CV disease during follow-up, and mediation analysis were performed in adults and adolescents separately. Among adults, EmE was associated with a 38% increased risk of DD 13 years later [odds ratio = 1.38 (1.05; 1.83)]. Stress level mediated 31.9% of this association (P = 0.01). Emotional eating was positively associated with cfPWV (β=0.02 [0.01; 0.04]). External eating was slightly associated with lower cfPWV (β=-0.03 [-0.05; -0.01]). No associations were observed between EB dimensions and metabolic syndrome. Energy intake was not found to be a mediator of any associations., Conclusion: Our results suggest that CV prevention should also take into account EB and include emotion regulation skills teaching., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Anterior segment optical coherence tomography (AS-OCT), being non-invasive and well-tolerated, is the method of choice for an in vivo investigation of ciliary muscle morphology and function. The analysis requires the segmentation of the ciliary muscle, which is, when performed manually, both time-consuming and prone to examiner bias. Here, we present a convolutional neural network trained for the automatic segmentation of the ciliary muscle in AS-OCT images. Ciloctunet is based on the Freiburg U-net and was trained and validated using 1244 manually segmented OCT images from two previous studies. An accuracy of 97.5% for the validation dataset was achieved. Ciloctunet's performance was evaluated by replicating the findings of a third study with 180 images as the test data. The replication demonstrated that Ciloctunet performed on par with two experienced examiners. The intersection-over-union index (0.84) of the ciliary muscle thickness profiles between Ciloctunet and an experienced examiner was the same as between the two examiners. The mean absolute error between the ciliary muscle thickness profiles of Ciloctunet and the two examiners (35.16 µm and 45.86 µm) was comparable to the one between the examiners (34.99 µm). A statistically significant effect of the segmentation type on the derived biometric parameters was found for the ciliary muscle area but not for the selective thickness reading ("perpendicular axis"). Both the inter-rater and the intra-rater reliability of Ciloctunet were good to excellent. Ciloctunet avoids time-consuming manual segmentation, thus enabling the analysis of large numbers of images of ample study cohorts while avoiding possible examiner biases. Ciloctunet is available as open-source.

Background: In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial., Methods: In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] <50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses., Results: Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16-2.72; P = .0084), lower baseline HIV-1 RNA levels (<100 000; aOR, 2.29; 95% CI, 1.33-3.96; P = .0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56-3.62; P < .0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI, .71-.92; P = .0018)., Conclusions: In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA <100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Presbyopia describes the eye's physiological loss of the ability to see close objects clearly. The adaptation to different viewing distances, termed accommodation, is achieved by a change in the curvature of the eye lens induced by the ciliary muscle. A possible approach to correct presbyopia could be to detect the ciliary muscle's neuromuscular signals during accommodation and transfer these signals electronically to a biomimetic, micro-optical system to provide the necessary refractive power. As a preliminary step toward such a described system, a novel three-dimensional and biocompatible lift-off method was developed. In addition, the influence of the distance between the electrically conducting surfaces of the lens on the accommodated signal amplitudes was investigated. Compared to the conventional masking methods, this process has the advantage that three-dimensional surfaces can be masked with biocompatible gelling sugar by utilizing a direct writing process with a dispensing robot. Since gelling sugar can be used at room temperature and is water-soluble, the process presented is suitable for materials that should not be exposed to organic solvents or excessively high temperatures. Apart from investigating the shrinkage behavior of the gelling sugar during the physical vapor deposition (PVD) coating process, this paper also describes the approaches used to partially coat a commercial scleral contact lens with an electrically conductive material. It was shown that gelling sugar withstands the conditions during the PVD processes and a successful lift-off was performed. To investigate the influence of the spacing between the electrically conductive regions of the contact lens on the measured signals, three simplified electrode configurations with different distances were fabricated using a 3D printer. By testing these in an experimental setup, it could be demonstrated that the distance between the conductive surfaces has a significant influence on the amplitude. Regarding the described lift-off process using gelling sugar, it was found that the dispensing flow rate has a direct influence on the line uniformity. Future work should address the influence of the viscosity of the gelling sugar as well as the diameter of the cannula. It is assumed that they are the prevailing limitations for the lateral resolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schumayer, Simon, Sittkus, Wagner, Bucher and Strasser.)

Background Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed ≈20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome-wide association study results highlighted multiple single-nucleotide polymorphisms on the SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele ( rs16890979 ) had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C-reactive protein) levels, estimated glomerular filtration rate variation (visit 1-V4), carotid intima-media thickness, and pulse wave velocity, rs16890979 was only associated with higher carotid intima-media thickness. Conclusions Our findings demonstrate that rs16890979 , a genetic determinant of SUA levels located on the SLC2A9 gene, is associated with carotid intima-media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease.

Background and Objectives: Statins are less efficacious in reducing cardiovascular disease risk in patients on dialysis than in the general population. Recent experimental data showed that phosphate excess promotes cellular de novo cholesterol synthesis through 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activation. Whether this mechanism might account for the resistance of patients on dialysis to statins has not yet been explored., Design, Setting, Participants, & Measurements: In this post hoc analysis, we examined the efficacy of statin treatment according to serum phosphate levels in the patients on dialysis who were participants of the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) trial using serum phosphate levels at baseline and during the trial course. We first classified the patients by groups of similar phosphate trajectories over time and tested whether phosphate as a longitudinal exposure (summarized by the identified trajectory groups) modulated the occurrence of major adverse cardiovascular events and all-cause death. We replicate the analysis in the Deutsche Diabetes Dialyze Studie (4D) trial., Results: In the AURORA trial, using multivariable analysis, we found that the treatment effect of statin on major adverse cardiovascular events and all-cause death was significant and protective effects in patients with low values of serum phosphate gradually faded for higher phosphate levels >5 mg/dl. A similar lack of statin treatment efficacy for both outcomes was observed with high baseline phosphate levels (>5 mg/dl). In the 4D trial, we found a comparable but not significant trend toward losing treatment efficacy in the presence of high serum phosphate levels for both outcomes., Conclusions: Our results demonstrated the limited treatment efficacy of statins in patients on dialysis in the presence of hyperphosphatemia., (Copyright © 2022 by the American Society of Nephrology.)

Background and Aims: Little is known about the effects of probiotics on inflammation in the context of chronic kidney disease (CKD). We investigated the association between probiotic intake and inflammation in patients with moderate-to-advanced CKD., Methods: We performed a cross-sectional study of 888 patients with stage 3-5 CKD and data on serum C-reactive protein (CRP) levels and a concomitant food frequency questionnaire. We estimated the odds ratios (ORs) [95% confidence interval (CI)] for various CRP thresholds (>3, >4, >5, >6, and >7 mg/L) associated with three intake categories (no yoghurt, ordinary yoghurt, and probiotics from yoghurts or dietary supplements) and two frequency categories (daily or less than daily)., Results: The 888 study participants (median age: 70; men: 65%) had a median estimated glomerular filtration rate of 28.6 mL/min/1.73 m 2 and a median [interquartile range] CRP level of 3.0 [1.6, 7.0] mg/L. Fifty-seven percent consumed ordinary yoghurt and 30% consumed probiotic yoghurt. The median intake frequency for yoghurt and probiotics was 7 per week. Relative to participants not consuming yoghurt, the ORs [95% CI] for CRP > 6 or >7 mg/L were significantly lower for participants consuming ordinary yoghurt (0.58 [0.37, 0.93] and 0.57 [0.35, 0.91], respectively) and for participants consuming probiotics (0.54 [0.33, 0.9] and 0.48 [0.28, 0.81], respectively), independently of age, sex, body mass index, CKD stage, cardiovascular disease, and fibre, protein and total energy intakes. The ORs were not significantly lower for CRP thresholds >3, >4, and >5 mg/L and were not significantly greater in daily consumers than in occasional consumers., Conclusion: We observed independent associations between the consumption of yoghurt or probiotics and lower levels of inflammation in patients with CKD. There was no evidence of a dose-effect relationship., Clinical Trial Registration: [https://www.clinicaltrials.gov/ct2/show/NCT03381950], identifier [NCT03381950]., Competing Interests: SW received a grant from ISN-H4KH Initiative, outside the submitted work. LK received a grant from Fresenius Kabi outside the submitted work, together with consulting fees from AstraZeneca, Dr. Shäre, and Fresenius Kabi. DF received a grant from Fresenius Medical Care outside the submitted work, consulting fees from Fresenius Kabi and Sanofi, and honoraria from Lilly Fresenius Kabi, Sanofi, Vifor, and Astellas. ZM received honoraria from AstraZeneca and Boehringer Ingelheim. M-CB-R received honoraria from MAYOLY SPINDLER and GILEAD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wagner, Merkling, Metzger, Koppe, Laville, Boutron-Ruault, Frimat, Combe, Massy, Stengel and Fouque.)

Background: Optimal daily water intake to prevent chronic kidney disease (CKD) progression is unknown. Taking the kidney's urine-concentrating ability into account, we studied the relation of kidney outcomes in patients with CKD to total and plain water intake and urine volume., Methods: Including 1265 CKD patients [median age 69 years; mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from the Chronic Kidney Disease-Renal Epidemiology and Information Network cohort (2013-19), we assessed fluid intake at baseline interviews, collected 24-h urine volumes and estimated urine osmolarity (eUosm). Using Cox and then linear mixed models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney failure and eGFR decline associated with hydration markers, adjusting for CKD progression risk factors and eUosm., Results: Patients' median daily intake was 2.0 L [interquartile range (IQR) 1.6-2.6] for total water and 1.5 L (1-1.7) for plain water, median urine volume was 1.9 L/24 h (IQR 1.6-2.4) and mean eUosm was 374 ± 104 mosm/L. Neither total water intake nor urine volume was associated with either kidney outcome. Kidney failure risk increased significantly with decreasing eUosm ˂292 mosm/L. Adjusted HRs (95% CIs) for kidney failure associated with plain water intake were 1.88 (1.02-3.47), 1.59 (1.06-2.38), 1.76 (0.95-3.24) and 1.55 (1.03-2.32) in patients drinking <0.5, 0.5-1.0, 1.5-2.0 and >2.0 L/day compared with those drinking 1.0-1.5  L/day. High plain water intake was also significantly associated with faster eGFR decline., Conclusions: In patients with CKD, the relation between plain water intake and progression to kidney failure appears to be U-shaped. Both low and high intake may not be beneficial in CKD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Aims: Long-chain polyunsaturated fatty acids (PUFAs) generate diverse bioactive lipid mediators, which tightly regulate vascular inflammation. The effects of omega-3 PUFA supplementation in cardiovascular prevention however remain controversial. In addition to direct dietary intake, fatty acid desaturases (FADS) determine PUFA levels. Increased arterial stiffness represents an independent predictor of mortality and cardiovascular events. The aim of the present study was to determine the association of PUFA intake, FADS1 genotype, and FADS expression with arterial stiffness., Methods and Results: A cross-sectional population-based cohort study of 1464 participants without overt cardiovascular disease was conducted. Dietary intake was assessed using a food frequency questionnaire. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), and the FADS1 locus variant was determined. Blood cell transcriptomics was performed in a subset of 410 individuals. Pulse wave velocity was significantly associated with the FADS1 locus variant. Differential associations between PWV and omega-3 PUFA intake were observed depending on the FADS1 genotype. High omega-3 PUFA intake attenuated the FADS1 genotype-dependent associations. Carriers of the minor FADS1 locus variant exhibited increased expression of FADS2, which is associated with PWV., Conclusion: Taken together, these findings point to FADS1 genotype-dependent associations of omega-3 PUFA intake on subclinical cardiovascular disease. These findings may have implications for identifying responders and non-responders to omega-3 PUFA supplementation and open up for personalized dietary counselling in cardiovascular prevention., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: Elevated brain natriuretic peptide (BNP) and the N-terminal fragment of its pro-hormone (NT-proBNP) have become established biomarkers for heart failure and are associated with cardiovascular morbidity and mortality. Investigating sources of inter-individual heterogeneity, particularly genetic factors, could help better identify patients at risk of future cardiovascular disease. The aim of this study was to estimate the heritability of circulating NT-proBNP levels, to perform a genome-wide association study (GWAS) and gene-candidate analysis focused on NPPB-NPPA genes on these levels, and to examine their association with cardiovascular or metabolic outcomes., Methods and Results: A total of 1555 individuals from the STANISLAS study were included. The heritability of circulating NT-proBNP levels was estimated at 15%, with seven single nucleotide polymorphisms (SNPs) reaching the significant threshold in the GWAS. All above SNPs were located on the same gene cluster constituted of MTHFR, CLCN6, NPPA, NPPB, and C1orf167. NPPA gene expression was also associated with NT-proBNP levels. Moreover, six other SNPs from NPPA-NPPB genes were associated with diastolic function (lateral e' on echocardiography) and metabolic features (glycated haemoglobin)., Conclusions: The heritability of natriuretic peptides appears relatively low (15%) and mainly based on the same gene cluster constituted of MTHFR, CLCN6, NPPA, NPPB, and C1orf167. Natriuretic peptide polymorphisms are associated with natriuretic peptide levels and diastolic function. These results suggest that natriuretic peptide polymorphisms may have an impact in the early stages of cardiovascular and metabolic disease., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: Beverages are an important aspect of diet, and their quality can possibly affect health. The Healthy Beverage Index (HBI) has been developed to take into account these effects. This study aimed to highlight the relationships between health and beverage quality by assessing the association of the HBI and its components with kidney and cardiometabolic (CM) outcomes in an initially healthy population-based familial cohort. Methods: This study included 1,271 participants from the STANISLAS cohort. The HBI, which includes 10 components of habitual beverage consumption, was calculated. Associations of the HBI and its components with estimated glomerular filtration rate (eGFR), albuminuria, hypertriglyceridemic waist (HTG waist), metabolic syndrome (MetS), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LV mass) were analyzed using multivariable linear or logistic regression models. Results: The median HBI score was 89.7 (78.6-95) out of 100 points. While the overall HBI score was not significantly associated with any of the studied outcomes, individual HBI components were found differently associated with the outcomes. cfPWV and cIMT were lower in participants who did not meet the full-fat milk criteria ( p = 0.03 and 0.001, respectively). In men, higher cfPWV was observed for the "low Fat milk" ( p = 0.06) and "alcohol" ( p = 0.03) non-adherence criteria. Odds of HTG waist were higher with the non-adherence to sugar-sweetened beverages criteria ( p < 0.001). eGFR was marginally higher with non-adherence to the coffee/tea criteria ( p = 0.047). Conclusions: In this initially healthy population, HBI components were differently associated with kidney and cardiometabolic outcomes, despite a good overall HBI score. Our results highlight specific impacts of different beverage types and suggest that beverages could have an impact on kidney and cardiometabolic health., Competing Interests: SW reports a grant from the International Society of Nephrology, outside of the submitted work. PR received grants and personal fees from Vifor Fresenius Medical Care Renal Pharma, personal fees from Idorsia, personal fees from KBP, Sanofi, NovoNordisk, personal fees from Ablative Solutions, non-financial support from G3P, personal fees from Corvidia, grants, personal fees from Relypsa a Vifor company and Vifor, personal fees from CardioRenal, grants and personal fees from AstraZeneca, grants and personal fees from Bayer, grants and personal fees from CVRx, personal fees from Fresenius, grants and personal fees from Novartis, personal fees from Grunenthal, personal fees from Servier, personal fees from Stealth Peptides, and all outside the submitted work. NG reports personal fees outside of the submitted work from Novartis, Vifor and AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wagner, Merkling, Girerd, Bozec, Van den Berghe, Hoge, Guillaume, Kanbay, Cakir-Kiefer, Thornton, Boivin, Mercklé, Laville, Rossignol and Nazare.)

The prognosis of metastatic colorectal cancer (CRC) remains poor. Patients and physicians are in need of individual therapies and precise response predictions. We investigated the predictive capacity of primary tumour material for treatment response of metastases. Mutational landscapes of primary tumours and corresponding metastases of 10 CRC patients were compared. Cell line characteristics and chemosensitivity were investigated pairwise for primary and metastatic tumours of four patients. PDX models of one patient were treated in vivo for proof of concept. Driver mutations did not differ between primaries and metastases, while the latter accumulated additional mutations. In vitro chemosensitivity testing revealed no differences for responses to 5-FU and oxaliplatin between primary and metastatic cell lines. However, irinotecan response differed significantly: the majority of metastases-derived cell lines was less sensitive to irinotecan than their matching primary counterpart. Therapy recommendations based on these findings were compared to clinical treatment response and mostly in line with the predicted outcome. Therefore, primary tumour cell models seem to be a good tool for drug response testing and conclusion drawing for later metastases. With further data from tumour-derived cell models, such predictions could improve clinical treatment decisions, both recommending likely effective therapeutic options while excluding ineffective treatments.

Background: There is limited evidence available identifying best practices to promote and sustain optimal outpatient-to-inpatient handoff processes to ensure safe and reliable continuity of care., Local Problem: A sentinel event occurred during the transition of care from the outpatient-to-inpatient setting. A root cause analysis revealed that the facility's standard operating procedure for patient handoffs was not consistently followed., Methods: A Lean Six Sigma approach was used to improve patient transfer with the implementation of a Situation-Background-Assessment-Recommendation handoff policy. Inferential and statistical process control methods were used to assess performance outcomes pre- and postdissemination., Results: Over 36 months there was a slow, steady decrease in patient transfer time including reduced variability. The most significant improvement effect occurred in the third year with a 50% reduction in transfer time., Conclusions: Longitudinal monitoring provides the opportunity to accurately identify beneficial outcomes, which develop downstream from initial quality improvement efforts., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis. All other APOBEC3 family members, including APOBEC3B, fail to promote liver tumor formation. Tumor DNA sequences from APOBEC3A-expressing animals display hallmark APOBEC signature mutations in TCA/T motifs. Bioinformatic comparisons of the observed APOBEC3A mutation signature in murine tumors, previously reported APOBEC3A and APOBEC3B mutation signatures in yeast, and reanalyzed APOBEC mutation signatures in human tumor datasets support cause-and-effect relationships for APOBEC3A-catalyzed deamination and mutagenesis in driving multiple human cancers., Competing Interests: Disclosures: D.A. Largaespada reported other from NeoClone Biotechnology, Inc., personal fees from BmoGen Biotechnology, Inc., other from Luminary Therapeutics, Inc., other from Recombinetics, Inc., other from ImmuSoft, Inc., and grants from Genentech, Inc. outside the submitted work. R.S. Harris reported personal fees from ApoGen Biotechnologies outside the submitted work. No other disclosures were reported., (© 2020 Law et al.)

Background: Recent studies have shown that hyperuricemia may be associated with incident hypertension (HTN). We examined whether serum uric acid (SUA) is a predictor of HTN and target organ damage (TOD) 20 years later in initially healthy middle-aged individuals., Methods: Participants from the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) a single-center familial longitudinal cohort study (961 initially healthy adults and 570 children) underwent clinical and laboratory measurements at baseline and after approximately 20 years. Blood pressure (BP: using ambulatory BP measurements), urine albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), diastolic dysfunction, and carotid-femoral pulse wave velocity (PWV) were measured at the end of follow-up., Results: In the parent population, higher baseline or last SUA levels and higher change in SUA (ΔUA) were significantly associated with an increased risk of HTN development, even after adjusting for known HTN risk factors (all P < 0.01). Higher baseline SUA was marginally associated with an increased risk of having high carotid-femoral PWV (P = 0.05). The association of SUA with BP increase was body mass index dependent (the increase in BP being greater in leaner subjects; interactionp < 0.05), and the association of SUA with eGFR decline was age dependent (the decline in eGFR being greater in older subjects; interactionp < 0.05). There was no significant association between SUA and diastolic dysfunction or LVH. In the whole population (i.e. including children), a significant association between SUA at baseline and the risk of HTN and higher carotid-femoral PWV was also found (both P < 0.02)., Conclusions: Increased SUA is associated with the development of HTN and vascular/renal TOD in initially healthy midlife subjects., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease., Design: To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort)., Methods: A total of 1506 participants attended both the visit 1 and visit 4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjusted for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed., Results: People who developed pre-diabetes (n = 555) and/or T2D (n = 73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable selection, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the circulating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D., Conclusions: The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic component, was associated with both the development and presence of pre-diabetes and T2D.

Presbyopia and myopia research shows a growing interest in ciliary muscle biometry using optical coherence tomography (OCT). Until now, segmentation of the ciliary muscle is often performed manually using either custom-developed programs or image processing software. Here we present a novel software for semi-automatic segmentation of the ciliary muscle. It provides direct import of OCT images in DICOM format, a standardized procedure for segmentation, image distortion correction, the export of anatomical ciliary muscle landmarks, like ciliary muscle apex and scleral spur, as well as a continuous thickness profile of the ciliary muscle as a novel way of analysis. All processing steps are stored as XML files, fostering documentation and reproducibility of research through the possibility of replicating the analysis. Additionally, CilOCT supports batch processing for the automated analysis of large numbers of images and the respective data export to tabulated text files based on the stored XML files. CilOCT was successfully applied in several studies and their results will be summarized in this paper., Competing Interests: The authors have declared that no competing interests exist.

Objectives : Stimulus preference assessments are a systematic, observation-based approach for identifying preferences among individuals with impaired communication skills. The purpose of this paper is to provide a review of the existing empirical literature that has utilized these methods with persons who have neurocognitive disorder (NCD). Methods : Studies were identified by searching online databases using a variety of search terms. Articles were included in the review if they were peer-reviewed, in English, were empirical in nature, and conducted a stimulus preference assessment with older adults diagnosed with NCD. Results : Eleven articles met the search criteria. Results revealed that data from stimulus preference assessments could increase activity engagement, increase requests for preferred items, identify reinforcers, and reduce behavioral and psychological symptoms. Conclusions : A small body of empirical literature suggests that data derived from stimulus preference assessments can be used to improve the lives of persons with NCD and their caregivers. Additional research is needed, however, to determine how effectively these procedures can be implemented into everyday practice in long-term care facilities. Clinical Implications : Stimulus preference assessments may provide a clinically useful means for efficiently identifying preferences in persons with severe NCD who cannot verbalize their needs.

Background The diet impact on cardiovascular diseases has been investigated widely, but the association between dietary patterns (DPs) and subclinical cardiovascular damage remains unclear. More informative DPs could be provided by considering metabolic syndrome components as intermediate markers. This study aimed to identify DPs according to generation and sex using reduced-rank regression (RRR) with metabolic syndrome components as intermediate markers and assess their associations with intima-media thickness, left ventricular mass, and carotid-femoral pulse-wave velocity in an initially healthy population-based family study. Methods and Results This study included 1527 participants from the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort fourth examination. DPs were derived using reduced-rank regression according to generation (G1: age ≥50 years; G2: age <50 years) and sex. Associations between DPs and cardiovascular damage were analyzed using multivariable linear regression models. Although identified DPs were correlated between generations and sex, qualitative differences were observed: whereas only unhealthy DPs were found for both men generations, healthy DPs were identified in G2 ("fruity desserts") and G1 ("fiber and w3 oil") women. The "alcohol," "fast food and alcohol," "fried, processed, and dairy products," and "meat, starch, sodas, and fat" DPs in G1 and G2 men and in G1 and G2 women, respectively, were associated with high left ventricular mass (β [95% CI], 0.23 [0.10-0.36], 0.76 [0.00-1.52], 1.71 [0.16-3.26], and 1.80 [0.45-3.14]). The "alcohol" DP in G1 men was positively associated with carotid-femoral pulse-wave velocity (0.22 [0.09-0.34]). Conclusions The DPs that explain the maximum variation in metabolic syndrome components had different associations with subclinical cardiovascular damage across generation and sex. Our results indicate that dietary recommendations should be tailored according to age and sex. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01391442.

Biofeedback training has been used to access autonomically-controlled body functions through visual or acoustic signals to manage conditions like anxiety and hyperactivity. Here we examined the use of auditory biofeedback to improve accommodative responses to near visual stimuli in patients wearing single vision (SV) and multifocal soft contact lenses (MFCL). MFCLs are one evidence-based treatment shown to be effective in slowing myopia progression in children. However, previous research found that the positive addition relaxed accommodation at near, possibly reducing the therapeutic benefit. Accommodation accuracy was examined in 18 emmetropes and 19 myopes while wearing SVCLs and MFCLs (centre-distance). Short periods of auditory biofeedback training to improve the response (reduce the lag of accommodation) was performed and accommodation re-assessed while patients wore the SVCLs and MFCLs. Significantly larger accommodative lags were measured with MFCLs compared to SV. Biofeedback training effectively reduced the lag by ≥0.3D in individuals of both groups with SVCL and MFCL wear. The training was more effective in myopes wearing their habitual SVCLs. This study shows that accommodation can be changed with short biofeedback training independent of the refractive state. With this proof-of-concept, we hypothesize that biofeedback training in myopic children wearing MFCLs might improve the treatment effectiveness.

Previous work suggested an association between near vision and myopia. We therefore investigated the accommodation process in emmetropes and myopes regarding morphologic changes of the ciliary muscle (CM) and power changes of the lens for different accommodation demands. The temporal CM of 18 emmetropic and 20 myopic students was imaged via anterior segment optical coherence tomography during far and near accommodation (2.5D, 3D, 4D). Additionally, accommodation dynamics to the stimuli pattern far-near-far (15 s each; 2.5D, 3D, 4D) were recorded with eccentric infrared photorefraction. OCT images were processed using custom-developed software facilitating the analysis of selective CM thickness (CMT) readings and CMT profiles. Anterior CMT readings were significantly smaller in myopes. Starting at 1.4 mm posterior to the scleral spur (SP), myopic CM became thicker than emmetropic. Anterior CMT changes (ΔCMT) continuously increased with accommodation demand in myopes while emmetropic ΔCMT only increased from 2.5D to 3D. Compared to emmetropes, myopes showed smaller ΔCMT but increased CM movement relative to SP. There were no significant differences between the groups for accommodation changes from far to near vision and vice versa, velocity, microfluctuations, power spectra or lag of accommodation. At 4 D, larger ΔCMT were associated with lower lens changes for disaccommodation. While CM shape, movement, and thickness showed distinct differences depending on refractive error, emmetropes and myopes did not differ in their dynamic accommodation. Further analysis is necessary to evaluate whether the CM's anatomical shape or predispositions in its intramuscular constituents are causative factors in myopigenesis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Previous studies have shown a high level of noncompliance with recommendations on breastfeeding duration, especially in France. The objective was to describe the association between breastfeeding initiation and duration and the statutory duration of postnatal maternity leave, the gap between the end of legal maternity leave and the mother's return to work, and maternal working time during the first year post-partum. Analyses were based on 8,009 infants from the French nationwide ELFE cohort. We assessed the association with breastfeeding initiation by using logistic regression and, among breastfeeding women, with categories of breastfeeding duration by using multinomial logistic regression. Among primiparous women, both postponing return to work for at least 3 weeks after statutory postnatal maternity leave (as compared with returning to work at the end of the statutory period) and working less than full-time at 1 year post-partum (as compared with full-time) were related to higher prevalence of breastfeeding initiation. Among women giving birth to their first or second child, postponing the return to work until at least 15 weeks was related to a higher prevalence of long breastfeeding duration (at least 6 months) as compared with intermediate duration (3 to <6 months). Working part-time was also positively related to breastfeeding duration. Among women giving birth to their third child or more, working characteristics were less strongly related to breastfeeding duration. These results support extending maternity leave or working time arrangements to encourage initiation and longer duration of breastfeeding., (© 2019 John Wiley & Sons Ltd.)

There is evidence for a possible link between myopia development and near vision. We investigated the effect of prolonged nearwork on ciliary muscle (CM) morphology and accommodation in 18 myopic and 17 emmetropic subjects (age 19 to 25). The CM was imaged during far (0.25 D) and near vision (4 D) using optical coherence tomography (OCT), and accommodation to a step pulse (0.25 D - 4 D - 0.25 D, 15 s each) was assessed by eccentric infrared photorefraction before and after a 30-min reading task at 25 cm. OCT images were analyzed using a custom-developed semi-automatic segmentation algorithm to determine CM thickness (CMT) profiles and selective CMT readings. Accommodation was assessed using a non-linear model. On average, the CM got thinner after nearwork, predominantly at 0.0-1.4 mm posterior to the scleral spur in emmetropes, and at 1.0-1.9 mm in myopes. Selective CMT readings confirmed a significant thinning after nearwork (univariate ANOVA F 1,66  = 26.313, p < 0.001), without any influence of the subjects' refractive state (F 1,66  = 1.887, p = 0.174) or the target distance (F 1,66  = 0.014, p = 0.907). The mean accommodation response for targets at infinity was significantly increased after nearwork (F 1,32  = 7.775, p = 0.009), with a larger myopic shift in myopes (F 1,32  = 11.310, p = 0.002). No change in velocity of accommodation was found. Sharing properties of striated muscles, the CM was expected to increase its thickness, but the opposite was found. Previous studies suggesting sustained nearwork to result in a CM spasm cannot be confirmed by the data presented here. Further research exploring the possible impact of sympathetic innervation is necessary as it is activated during intense nearwork., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale & Objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD)., Study Design: Prospective longitudinal cohort study., Setting & Participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study., Predictor: Fasting urinary osmolality measured using delta cryoscopy., Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51 Cr-EDTA renal clearance., Analytical Approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR., Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m 2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H 2 O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile., Limitations: Fasting was self-reported., Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Infants' olfactory experience begins before birth and extends after birth through milk and complementary foods. Until now, studies on the effects of chemosensory experience in utero and/or through human milk focused on experimentally controlled exposure to only 1 target food bearing a specific odor quality and administered in sizeable amounts. This study aimed to assess whether early olfactory experience effect was measurable in "everyday conditions" of maternal food intake during pregnancy and lactation, and of infant intake at weaning, leading to expose the infant to corresponding odors as fetus, neonate, and infant up to 8 and 12 months of age. Infants' early food exposures were assessed by asking mothers to fill out diaries about their food consumption during pregnancy and breastfeeding, and about their infant's consumption during complementary feeding. To test odor liking, odorants representing a priori pleasant and unpleasant food odors, as well as odorless stimuli, were presented. The infant's exploratory behavior toward odorized bottles and nonodorized control bottles was measured in terms of mouthing duration, which is thought to reflect attraction and/or appetence. At age 8 months only, positive correlations were found between liking of some unpleasant odors and early exposure to these odors through mother's diet. No correlations were found between infants' liking of the pleasant odors and early exposures to the foods bearing these odors. This study highlights that early exposure to unpleasant food odors may increase subsequent liking (or reduce subsequent dislike) of these food odors at least until the age of 8 months., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty ( SB ) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified SB -driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with FOXR2 activation. This represents the first genetically induced mouse model of CNS-PNET and a rare model of group 3 and 4 medulloblastoma. We identified several putative proto-oncogenes including Arhgap36, Megf10 , and Foxr2 . Genetic manipulation of these genes demonstrated a robust impact on tumorigenesis in vitro and in vivo . We also determined that FOXR2 interacts with N-MYC, increases C-MYC protein stability, and activates FAK/SRC signaling. Altogether, our study identified several promising therapeutic targets in medulloblastoma and CNS-PNET. SIGNIFICANCE: A transposon-induced mouse model identifies several novel genetic drivers and potential therapeutic targets in medulloblastoma and CNS-PNET., (©2019 American Association for Cancer Research.)

The incidence of malignant melanoma has increased over the past two decades. A combined BRAF/MEK inhibitor regimen has been shown to lead to prolonged survival and progression-free survival in patients with metastatic BRAF V600-mutant melanoma. Different nephrotoxic effects have been described, among them hyponatremia. The goal of the present narrative review was to understand the pathophysiological mechanisms driving hyponatremia when using selective BRAF inhibitors and/or MEK inhibitors in order to propose potential strategies to prevent or to treat this side effect. Several mechanisms of kidney injury have been suggested including changes in glomerular and tubular function. However, the precise mechanisms of hyponatremia remain unknown. Our hypothesis is that BRAF/MEK inhibitors lead to hyponatremia and water retention (so-called dilution hyponatremia) by activating aquaporin 2 (AQP2) trafficking from its intracellular compartment to the luminal cell membrane, and by activating ENaC channel. Therefore, we recommend treating the hyponatremia related to BRAF/MEK inhibitors with restriction of fluid intake., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the role of the mother's mother and mothers' previous personal experiences with breastfeeding and childcare in breastfeeding practices., Design and Setting: The analysis included 13,774 mother-infant dyads from the French national birth cohort ELFE. Feeding practices were assessed by face-to-face interview in maternity wards in 2011, by phone interviews at months 2 and 12 post-partum and by Internet/paper questionnaires monthly from months 3-10. Sociodemographic, maternal and newborn-related factors were collected in the maternity unit and by postnatal phone interview at month 2. Multivariable logistic and linear regression was used to assess the association of mother's mother and mothers' previous personal experiences with breastfeeding initiation and duration., Findings: Previous breastfeeding experience (i.e., whether mothers had breastfed their previous children) was positively associated with both breastfeeding initiation and duration. Mothers who had been breastfed themselves as infants were more likely to initiate and continue breastfeeding than non-breastfed mothers. Conversely, non-breastfed mothers who had received care advice from their own mother were less likely to start and maintain breastfeeding. The effect of having been breastfed in infancy was especially important for primiparous mothers and to a lesser extent, multiparous mothers with no previous breastfeeding experience. Also, formal experience in childcare, in a professional context, was associated with breastfeeding initiation but not duration., Key Conclusions and Implications for Practice: Mother's mother and mother's previous breastfeeding experience have a strong influence on breastfeeding practices. Breastfeeding interventions should be tailored to the mother's level of experience and should provide extra support for multiparous mothers with no previous breastfeeding experience., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Therapeutic options for the treatment of colorectal cancer (CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hyper-mutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens (TAAs) and tumor-specific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptide-based vaccines achievable by adjuvants and immune-stimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens - in CRC almost exclusively neoantigens - which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immune-stimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

[This corrects the article on p. 5100 in vol. 9, PMID: 30319924.].

Background: HIV epidemics disproportionately affect transwomen worldwide. Trans-specific guidance, outreach, and interventions to increase pre-exposure prophylaxis (PrEP) use among transwomen are scarce., Setting: Rio de Janeiro, Brazil., Methods: We measured awareness and willingness to use PrEP and examined factors associated with those outcomes among transwomen in Rio de Janeiro and estimated how many transwomen would be eligible for PrEP. Data originate from Transcender study, a respondent-driven sampling survey conducted from August 2015 to January 2016. We performed regression models for PrEP awareness and willingness., Results: One hundred thirty-one (38.0%) of 345 participants had heard of PrEP. Among transwomen who self-reported as HIV-negative, 162 (76.4%, N = 212 with available data) reported willingness to use it and 163 (66.8%, N = 244) met PrEP behavioral eligibility criteria. Transwomen with health access in the previous 6 months who reported HIV-infected sexual partner and with 8+ years of schooling had increased odds of PrEP awareness. Lower PrEP awareness was associated with condomless anal intercourse and newly diagnosed HIV infection. Younger age and perceiving themselves at risk of HIV infection increased the odds of PrEP willingness. Lower odds of PrEP willingness were associated with concerns about long-term effects of PrEP and with difficulties in getting access to health care due to transphobia., Conclusion: Combination of low awareness, high willingness, and substantial PrEP eligibility corroborates transwomen as a key population for HIV prevention. PrEP is a promising and empowering strategy for HIV prevention among transwomen, but trans-specific recommendations are needed to effectively implement PrEP in this population.

The purpose of this study was to provide an in-depth analysis of the ciliary muscle's (CM) morphological changes during accommodation by evaluating CM thickness (CMT) profiles. The CM of 15 near-emmetropic subjects (age 20-39) was imaged via optical coherence tomography (OCT) during far (0 D) and near vision (3 D). A custom-made Java-based program was used for semi-automatic CM segmentation and thickness measurements. CMT profiles were generated to determine regions of the largest shape changes. The results revealed on average a thinning within the first 0.25 mm and a thickening from 0.36 to 1.48 mm posterior to scleral spur when accommodating from 0 to 3 D. In contrast to previous analyses, this method offers pixel-wise reconstruction of CM shapes and quantification of accommodative change across the entire muscle boundary., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

The objectives of this study were to estimate the age of complementary feeding introduction (CFI) and investigate the related health, demographic, and socio-economic factors. Analyses were based on 10,931 infants from the French national birth cohort ELFE, born in 2011. Health, demographic, and socio-economic data concerning infants and parents were collected at birth (face-to-face interviews and medical records) and 2 months (telephone interviews). Data on milk feeding and CFI practices were collected at birth and 2 months then monthly from 3 to 10 months using online or paper questionnaires. The associations between both health and social factors and CFI age were tested by multivariable multinomial logistic regressions. The mean CFI age was 5.2 ± 1.2 months; 26% of the infants started complementary feeding before 4 months of age (CF < 4 months), 62% between 4 and 6 months of age, and 12% after 6 months of age (CF > 6 months). CF < 4 months was more likely when mothers smoked, were overweight/obese, younger (<29 years), and used their personal experience as an information source in child caregiving and when both parents were not born in France. CF < 4 months was less likely when the infant was a girl, second-born, when the mother breastfed longer, and had attended at least one birth preparation class. Mothers of second-born infants and who breastfed their child longer were more likely to introduce CF > 6 months. Couples in which fathers were born in France and mothers were not born in France were less likely to introduce CF > 6 months. CF < 4 months occurred in more than 25% of the cases. It is important to continue promoting clear CFI recommendations, especially in smoking, overweight, young, not born in France, and nonbreastfeeding mothers., (© 2017 John Wiley & Sons Ltd.)

Breastfeeding is recommended until 6 months of age, but a wide range of infant formula is available for nonbreastfed or partially breastfed infants. Our aim was to describe infant formula selection and to examine social- and health-related factors associated with this selection. Analyses were based on 13,291 infants from the French national birth cohort Etude Longitudinale Française depuis l'Enfance. Infant diet was assessed at Month 2 by phone interview and monthly from Months 3 to 10 via internet/paper questionnaires. Infant formulas were categorized in 6 groups: extensively or partially hydrolysed, regular with or without prebiotics/probiotics, and thickened with or without prebiotics/probiotics. Associations between type of infant formula used at 2 months and family or infant characteristics were assessed by multinomial logistic regressions. At Month 2, 58.1% of formula-fed infants were fed with formula enriched in prebiotics/probiotics, 31.5% with thickened formula, and 1.4% with extensively hydrolysed formula. The proportion of formula-fed infants increased regularly, but the type of infant formula used was fairly stable between 2 and 10 months. At Month 2, extensively hydrolysed formulas were more likely to be used in infants with diarrhoea or regurgitation problems. Partially hydrolysed formulas were more often used in families with high income, with a history of allergy, or with infants with regurgitation issues. Thickened formulas were used more with boys, preterm infants, infants with regurgitation issues, or in cases of early maternal return to work. The main factors related to the selection of infant formula were family and infant health-related ones., (© 2017 John Wiley & Sons Ltd.)

Hepatic steatosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet little is known about the molecular pathology associated with this factor. In this study, we performed a forward genetic screen using Sleeping Beauty (SB) transposon insertional mutagenesis in mice treated to induce hepatic steatosis and compared the results to human HCC data. In humans, we determined that steatosis increased the proportion of female HCC patients, a pattern also reflected in mice. Our genetic screen identified 203 candidate steatosis-associated HCC genes, many of which are altered in human HCC and are members of established HCC-driving signaling pathways. The protein kinase A/cyclic AMP signaling pathway was altered frequently in mouse and human steatosis-associated HCC. We found that activated PKA expression drove steatosis-specific liver tumorigenesis in a mouse model. Another candidate HCC driver, the N -acetyltransferase NAT10 , which we found to be overexpressed in human steatosis-associated HCC and associated with decreased survival in human HCC, also drove liver tumorigenesis in a steatotic mouse model. This study identifies genes and pathways promoting HCC that may represent novel targets for prevention and treatment in the context of hepatic steatosis, an area of rapidly growing clinical significance. Cancer Res; 77(23); 6576-88. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: A balanced diet is essential to slowing the progression of chronic kidney disease (CKD) and managing the symptoms. Currently, no tool is available to easily and quickly assess energy and macronutrient intake in patients with non end-stage CKD. We aimed to develop and evaluate the validity and reproducibility of a new short 49-item food frequency questionnaire (SFFQ) adapted to patients with CKD., Methods: The CKD-REIN study is a prospective cohort that enrolled 3033 patients with moderate or advanced CKD from a national sample of nephrology clinics. A sub-sample of 201 patients completed the SFFQ twice, at a one-year interval and were included in the reproducibility study. During this interval, 127 patients also completed six 24-h recalls and were included in the validity study. Main nutrient and dietary intakes were computed. Validity was evaluated by calculating crude, energy-adjusted and de-attenuated correlation coefficients (CC) between FFQ and the mean of the 24-h recall results. Bland-Altman plots were performed and cross-classification into quintiles of consumption of each nutrient and food group was computed. Reproducibility between the two SFFQs was evaluated by intraclass CC (ICC)., Results: Regarding validity, CC ranged from 0.05 to 0.79 (unadjusted CC, median: 0.40) and 0.10 to 0.59 (de-attenuated CC, median: 0.35) for food group and nutrient intakes, respectively. Five of the most important nutrients of interest in CKD, i.e. protein, calcium, phosphorus, potassium, and sodium had de-attenuated CC of 0.46, 0.43, 0.39, 0.32, and 0.12, respectively. The median of classification into the same or adjacent quintiles was 68% and 65% for food and nutrient intakes, respectively, and ranged from 63% to 69% for the five nutrients mentioned before. Bland-Altman plots showed good agreement across the range of intakes. ICC ranged from 0.18 to 0.66 (median: 0.46)., Conclusions: The CKD-REIN SFFQ showed acceptable validity and reproducibility in a sample of patients with CKD, notably for CKD nutrients of importance. It can now be used in large-scale epidemiological studies to easily assess the relations between diet and CKD outcomes as well as in clinical routine. It may also serve as a basis for the development of FFQs in international CKD cohort networks.

Background: Low and high blood potassium levels are common and were both associated with poor outcomes in patients with chronic kidney disease (CKD). Whether such relationships may be altered in CKD patients receiving optimized nephrologist care is unknown., Methods: NephroTest is a hospital-based prospective cohort study that enrolled 2078 nondialysis patients (mean age: 59 ± 15 years, 66% men) in CKD stages 1 to 5 who underwent repeated extensive renal tests including plasma potassium (P K ) and glomerular filtration rate (GFR) measured (mGFR) by 51 Cr-EDTA renal clearance. Test reports included a reminder of recommended targets for each abnormal value to guide treatment adjustment. Main outcomes were cardiovascular (CV) and all-cause mortality before end-stage kidney disease (ESKD), and ESKD., Results: At baseline, median mGFR was 38.4 mL/min/1.73m 2 ; prevalence of low P K (<4 mmol/L) was 26.5%, and of high P K (>5 mmol/L) 6.4%; 74.4% of patients used angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). After excluding 137 patients with baseline GFR < 10 mL/min/1.73m 2 or lost to follow-up, 459 ESKD events and 236 deaths before ESKD (83 CV deaths) occurred during a median follow-up of 5 years. Compared to patients with P K within [4, 5] mmol/L at baseline, those with low P K had hazard ratios (HRs) [95% CI] for all-cause and CV mortality before ESKD, and for ESKD of 0.82 [0.58-1.16], 1.01 [0.52-1.95], and 1.14 [0.89-1.47], respectively, with corresponding figures for those with high P K of 0.79 [0.48-1.32], 1.5 [0.69-3.3], and 0.92 [0.70-1.21]. Considering time-varying P K did not materially change these findings, except for the HR of ESKD associated with high P K , 1.39 [1.09-1.78]. Among 1190 patients with at least two visits, P K had normalized at the second visit in 39.9 and 54.1% respectively of those with baseline low and high P K . Among those with low P K that normalized, ARB or ACEi use increased between the visits (68.3% vs 81.8%, P < .0001), and among those with high P K that normalized, potassium-binding resin and bicarbonate use increased (13.0% vs 37.0%, P < .001, and 4.4% vs 17.4%, P = 0.01, respectively) without decreased ACEi or ARB use., Conclusion: In these patients under nephrology care, neither low nor high P K was associated with excess mortality.

Introduction: Over the last few decades, the prevalence of obesity has increased dramatically. This increase has been mirrored by a rise in the risk of a number of health conditions, including hypertension, diabetes and chronic kidney disease. Although the weight loss following bariatric surgery has been shown to relieve the severity of diabetes and reduce hypertension, the effect on renal function has been less extensively evaluated., Objective: The aims of the present study were to: (i) compare the estimated glomerular filtration rate (eGFR, using the MDRD and CKD-EPI equations) and the calculated glomerular filtration rate (using the 24-hour urine volume) with the measured glomerular filtration rate (mGFR) assessed with the plasma iohexol clearance method in severely obese patients, and (ii) evaluate the effect of weight loss on the mGFR 6 months after bariatric surgery., Methods: Before and six months after bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy), eligible patients for bariatric surgery were admitted as day cases to the nephrology unit, where they underwent a plasma iohexol clearance test. The GFR was also estimated using the MDRD and CKDEPI equations and the 24-hour urine method. Changes in eGFR and mGFR were compared using a Wilcoxon test for paired data., Results: Data from 16 patients with severe obesity (mean ± standard deviation of Body Mass Index [BMI]: 43.9 ± 7.3 kg/m 2 ) were analyzed. At baseline, 12 (75%) presented with hypertension and 10 (63%) presented with diabetes. The median [range] iohexol clearance rate was 109 [57-194] mL/min. The plasma iohexol clearance test evidenced hyperfiltration (mGFR>120 mL/min) in 7 patients. In contrast, the eGFR values generated by the MDRD equation, the CKDEPI equation and the GFR MFR calculated with the 24-hour urine method only identified hyperfiltration in 1, 0 and 5 patients, respectively. Six months after surgery, the mean BMI had fallen significantly (P<0.0012), and the severity of diabetes (according to the HbA 1c level) had decreased significantly from 6.6 [6.0-9.8] % to 5.7 [5.2-8.6] % (P=0.025). The iohexol clearance rate increased slightly after bariatric surgery. Changes in BMI after surgery do not seem to be correlated with the changes in iohexol clearance. In patients displaying hyperfiltration at baseline, the mGFR fell significantly (n=7; P=0.01) and returned to near normal values. No significant changes in the eGFR were observed., Conclusion: Our results suggest that MDRD and CKD-EPI equations do not provide accurate estimates of the true GFR in severely obese patients (particularly in those with hyperfiltration). Iohexol clearance or other methods for determining mGFR should constitute the gold standard for the accurate evaluation of renal function in this context. Renal function (as evaluated by the mGFR) improved 6 months after bariatric surgery in severely obese individuals particularly in patients displaying hyperfiltration at baseline. However, these observations must be confirmed in a larger study with a longer follow-up period., (Copyright © 2016 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.)

Impaired 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)-dependent cortisol inactivation can lead to electrolyte dysbalance, hypertension and cardiometabolic disease. Furthermore, placental 11β-HSD2 essentially protects the fetus from high maternal glucocorticoid levels, and its impaired function has been associated with altered fetal growth and a higher risk for cardio-metabolic diseases in later life. Despite its important role, 11β-HSD2 is not included in current off-target screening approaches. To identify potential 11β-HSD inhibitors among approved drugs, a pharmacophore model was used for virtual screening, followed by biological assessment of selected hits. This led to the identification of several azole fungicides as 11β-HSD inhibitors, showing a significant structure-activity relationship between azole scaffold size, 11β-HSD enzyme selectivity and inhibitory potency. A hydrophobic linker connecting the azole ring to the other, more polar end of the molecule was observed to be favorable for 11β-HSD2 inhibition and selectivity over 11β-HSD1. The most potent 11β-HSD2 inhibition, using cell lysates expressing recombinant human 11β-HSD2, was obtained for itraconazole (IC 50 139±14nM), its active metabolite hydroxyitraconazole (IC 50 223±31nM) and posaconazole (IC 50 460±98nM). Interestingly, experiments with mouse and rat kidney homogenates showed considerably lower inhibitory activity of these compounds towards 11β-HSD2, indicating important species-specific differences. Thus, 11β-HSD2 inhibition by these compounds is likely to be overlooked in preclinical rodent studies. Inhibition of placental 11β-HSD2 by these compounds, in addition to the known inhibition of cytochrome P450 enzymes and P-glycoprotein efflux transport, might contribute to elevated local cortisol levels, thereby affecting fetal programming., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Chronic impaired renal function constitutes a major risk factor of morbi-mortality during the treatment of an abdominal aortic aneurism (AAA). The inflammatory state due to the AAA could result in a reduction in the muscular mass and an overestimation of the glomerular filtration rate (GFR) with the usual formulas. The objective of this study was to determine if the formulas used to evaluate the estimated GFR were adapted in patients with AAA., Materials and Methods: Between August 2013 and November 2014, we conducted an exploratory study to evaluate the renal function before surgery for AAA in 28 patients. The renal function was evaluated by (1) the dosage of plasmatic creatinine, (2) the GFR estimated with the Cockroft-Gault, Modification of Diet in Renal Disease (MDRD), and chronic kidney disease epidemiology collaboration (CKD-EPI) formulas, (3) the creatinine clearance (CC), and (4) the direct measurement of the GFR with a reference method (iohexol clearance). Statistical analysis was carried out to compare and correlate the GFR estimated by the various formulas with the GFR measured by the reference technique., Results: The study included 21 men (75%) and 7 women (25%), with a median age of 76 years (58-89). The measured GFR was correlated with the GFR estimated from the CKD-EPI (rho = 0.78, P < 0.0001), the MDRD (rho = 0.78, P < 0.0001), the Cockroft-Gault (rho = 0.65, P = 0.0002), and CC (rho = 0.86, P < 0.0001). However, there were important individual variations between estimated and measured GFR. As regards the detection of the patients presenting a GFR <60 mL/min/1.73 m 2 , the sensitivities of the CKD-EPI, MDRD, Cockroft-Gault formulas and CC were 64%, 64%, 71%, and 70%, respectively. Specificities were 71%, 79%, 57%, and 100%, respectively. The estimation of the GFR by the CKD-EPI formula had the lowest bias (-3.0). Bland-Altman plots indicated that the estimation of the GFR by the CKD-EPI formula had the best performance in comparison with the other methods., Conclusions: This study found a statistical correlation between the measurement of the GFR and the various formulas available to estimation the GFR among AAA patients. The CKD-EPI formula is most appropriate. However, there were important individual variations between the measurement and the estimations of the GFR. A larger scale study is necessary to determine the profile of the patients with a risk of error in the estimation of the GFR. The French recommendations on the evaluation of the renal function before AAA treatment remain based on serum creatinine and should be revalued., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 ± 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 ± 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.

The purpose of this study was to investigate whether a reduction of the accommodative lag is possible by training the accuracy of accommodation using auditory biofeedback. Accommodation responses were measured in thirty-one young adults with myopia for dioptric target distances of 2.0, 2.5, and 3.0D using an eccentric infrared photorefractor. For the biofeedback training, subjects were randomly assigned to an experimental (n=15) or a control group (n=16). Subjects of the experimental group were provided with two tones while fixating a target, one tone was related to their accommodative response and the second to the target distance. Their task was to match these tones. The control group did not receive any auditory biofeedback. Two different training methods were applied, a continuous training of 200s, and ten consecutive sessions of 20s each. The training effects on the lag of accommodation (change Δ) were highly variable. Regarding the entire study group, the observed change in the accommodative lag was greater at closer distances, while no difference between the two training methods was revealed. Nevertheless, seven experimental subjects reduced their lag by ⩾0.3D (3.0D target distance: Δ long =-0.29±0.20D, Δ short =-0.24±0.21D). This reduction was also seen in two control subjects. Remeasurement revealed that the average training effect cannot be preserved over a period of 5-7days. The current investigation has shown that the accuracy of accommodation can be trained in some subjects using auditory biofeedback for target distances of 2.5D or closer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)