The association of nutritional factors and skin autofluorescence in persons receiving hemodialysis

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycemia, oxidative stress and systemic inflammation. AGEs are also formed in food during cooking. On the other hand, malnutrition may contribute to AGE formation through its association with oxidative stress and inflammation. AGE accumulation can be measured by skin autofluorescence (SAF) and elevated SAF is independently associated with higher mortality on hemodialysis (HD). We aimed to investigate associations between SAF, dietary AGE intake and markers of malnutrition in persons receiving HD.Design and setting: single center cross-sectional study.Subjects: 120 participants on HD dialyzing at least three times per week for 3-4 hours.Main outcome measures: SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. Subjective Global Assessment was performed to evaluate nutritional status.Results: SAF was higher in malnourished participants and correlated negatively with serum albumin and cholesterol, HGS and energy, protein and fat intake and positively with C reactive protein and chronological age; SAF did not correlate with dietary AGE intake. Multivariable linear regression analysis showed that diabetes, smoking, serum albumin, HGS, protein intake and dialysis vintage were independent predictors of increased SAF.Conclusions: Markers of malnutrition were more important determinants of increased SAF than high dietary AGE intake in this HD population. Nutritional interventions aiming to reduce SAF by correcting malnutrition should therefore be investigated. The observed association between higher SAF and malnutrition may in part explain the previously reported association between higher SAF and mortality on HD

Factors associated with change in skin autofluorescence in persons receiving dialysis

IntroductionAn increase over time in skin autofluorescence (SAF), a measure of accumulation of advanced glycation end products (AGE), predicts higher mortality on hemodialysis (HD). However, evidence is lacking regarding factors that contribute to changes in SAF over time in populations on dialysis. We investigated the rate of change in SAF over 1 year and the factors associated with these changes.MethodsWe enrolled 109 patients on HD and 28 on peritoneal dialysis in a prospective study. SAF was measured at baseline, 3, 6, 9, and 12 months. Rate of change in SAF was calculated using the SLOPE function in Microsoft Excel (Microsoft, Redmond, WA). Participants were then grouped into those with stable SAF or increasing SAF. Dietary AGE intake and nutritional assessments were performed at baseline, 6, and 12 months.ResultsThe mean SAF trend observed was an increase of 0.30 ± 0.63 arbitrary units (AU) per year, but this varied from a decrease of 0.15 ± 0.44 to an increase of 0.76 ± 0.42 AU per year in stable and increasing SAF groups, respectively. Increasing SAF was more common in participants who developed malnutrition during the observation period, whereas those who became well-nourished were more likely to have stable SAF (8 [80%] vs. 14 [42%]; P = 0.02). Development/prevalence of malnutrition over 1 year, HD as first dialysis modality, and current smoking were independent predictors of increasing SAF.ConclusionSAF increases over time in most persons on dialysis. Independent determinants of increasing SAF were development/prevalence of malnutrition, HD as first dialysis modality, and current smoking. Strategies to reduce/prevent the rise in SAF, including prevention/correction of malnutrition, should be investigated in prospective studies

Extended Kramers-Moyal analysis applied to optical trapping

The Kramers-Moyal analysis is a well established approach to analyze stochastic time series from complex systems. If the sampling interval of a measured time series is too low, systematic errors occur in the analysis results. These errors are labeled as finite time effects in the literature. In the present article, we present some new insights about these effects and discuss the limitations of a previously published method to estimate Kramers-Moyal coefficients at the presence of finite time effects. To increase the reliability of this method and to avoid misinterpretations, we extend it by the computation of error estimates for estimated parameters using a Monte Carlo error propagation technique. Finally, the extended method is applied to a data set of an optical trapping experiment yielding estimations of the forces acting on a Brownian particle trapped by optical tweezers. We find an increased Markov-Einstein time scale of the order of the relaxation time of the process which can be traced back to memory effects caused by the interaction of the particle and the fluid. Above the Markov-Einstein time scale, the process can be very well described by the classical overdamped Markov model for Brownian motion.Comment: 14 pages, 18 figure

Combined electrical transport and capacitance spectroscopy of a MoS2−LiNbO3{\mathrm{MoS_2-LiNbO_3}} field effect transistor

We have measured both the current-voltage ($I_\mathrm{SD}$-$V_\mathrm{GS}$) and capacitance-voltage ($C$-$V_\mathrm{GS}$) characteristics of a $\mathrm{MoS_2-LiNbO_3}$ field effect transistor. From the measured capacitance we calculate the electron surface density and show that its gate voltage dependence follows the theoretical prediction resulting from the two-dimensional free electron model. This model allows us to fit the measured $I_\mathrm{SD}$-$V_\mathrm{GS}$ characteristics over the \emph{entire range} of $V_\mathrm{GS}$. Combining this experimental result with the measured current-voltage characteristics, we determine the field effect mobility as a function of gate voltage. We show that for our device this improved combined approach yields significantly smaller values (more than a factor of 4) of the electron mobility than the conventional analysis of the current-voltage characteristics only.Comment: to appear in Applied Physics Letter

Prospective study of change in skin autofluorescence over time and mortality in people receiving hemodialysis

Introduction: Elevated skin autofluorescence (SAF), a measure of tissue accumulation of advanced glycation end products (AGEs), is a strong predictor of all-cause and cardiovascular mortality in the hemodialysis population. However, prospective studies investigating the association between changes in SAF over time and mortality are scarce. We therefore aimed to investigate the prognostic value of SAF trend for predicting mortality in a hemodialysis population. Methods: We enrolled 120 patients on hemodialysis in a 5-year observational, prospective study. SAF was measured at baseline, 3, 6, 9, 12, and 24 months. Rate of change in SAF (i.e., SAF trend) was calculated using linear regression. Time to event was the number of days from baseline to death, kidney transplantation, or March 31, 2022. Results: Mean age, mean baseline SAF, and median SAF trend were 65 ± 14 years, 3.4 ± 0.9 arbitrary units (AU), and an increase of 0.1 (−0.1 to 0.4) AU/yr, respectively. Median observation time was 42 months, during which 59 participants (49%) died. Univariable analysis identified age, history of smoking, lower serum albumin, higher baseline SAF, and increase in SAF as significant predictors of higher mortality. In multivariable analysis, higher baseline SAF (hazard ratio: 1.45; 95% confidence interval: 1.08–1.94; P = 0.01) and increasing SAF trend (2.37 [1.43–3.93]; P < 0.001) were independent predictors of increased mortality. Conclusion: An increasing SAF trend and higher baseline SAF were independent predictors of all-cause mortality in this hemodialysis population, suggesting that monitoring of SAF may have clinical utility. Strategies to improve outcomes by reducing or preventing the increase in SAF should now be investigated in prospective studies

Skin autofluorescence and malnutrition as predictors of mortality in persons receiving dialysis: a prospective cohort study

BackgroundSkin autofluorescence (SAF), which is a measure of accumulation of advanced glycation end‐products (AGE), and malnutrition are each associated with higher mortality in dialysis populations, although no studies have investigated these potentially related associations together. We simultaneously assessed SAF and malnutrition as risk factors for mortality in persons receiving dialysis.MethodsSAF was measured in 120 haemodialysis and 31 peritoneal dialysis patients using an AGE Reader (DiagnOptics, Groningen, The Netherlands). Dietary AGE, energy, protein and fat intake, handgrip strength, anthropometry, biochemistry and Subjective Global Assessment were also evaluated. Time to event was days from baseline to death, kidney transplantation or 30 September 2018.ResultsMedian observation time was 576 days, during which 33 (21.9%) patients died. Those who died had higher baseline SAF levels [3.8 ± 1.0 versus 3.3 ± 0.8 arbitrary units (AU); P = 0.001] and were more likely to be malnourished (58% versus 31%; P = 0.006). Malnourished persons who died had higher SAF values than those who died but were well‐nourished (4.2 ± 1.1 versus 3.3 ± 0.7 AU; P = 0.007). Survival was significantly better in participants with baseline SAF below the median and in those well‐nourished than those with baseline SAF above the median and in those malnourished, respectively. Multivariable analysis identified SAF [hazards ratio (HR) = 1.44; 95% confidence interval (CI) = 1.05–1.97; P = 0.02], malnutrition (HR = 2.35; 95% CI = 1.16–4.78; P = 0.02) and chronological age (HR = 1.60; 95% CI = 1.10–2.33; P = 0.01) as independent predictors of mortality.ConclusionsAlthough higher SAF and malnutrition are potentially inter‐related, they were both independently associated with increased mortality in this population. Interventions to improve outcomes by reducing SAF through correction of malnutrition or dietary AGE restriction require testing in prospective studies

Impact of malnutrition on health-related quality of life in persons receiving dialysis: a prospective study

Health-related quality of life (HRQoL) is severely impaired in persons receiving dialysis. Malnutrition has been associated with some measures of poor HRQoL in cross-sectional analyses in dialysis populations, but no studies have assessed the impact of malnutrition and dietary intake on change in multiple measures of HRQoL over time. We investigated the most important determinants of poor HRQoL and the predictors of change in HRQoL over time using several measures of HRQoL. We enrolled 119 haemodialysis and 31 peritoneal dialysis patients in this prospective study. Nutritional assessments (Subjective Global Assessment [SGA], anthropometry and 24-hour dietary recalls) and HRQoL questionnaires (Short Form-36 [SF-36] mental [MCS] and physical component scores [PCS] and European QoL-5 Dimensions [EQ5D] health state [HSS] and visual analogue scores [VAS]) were performed at baseline, 6 and 12 months. Mean age was 64(14) years. Malnutrition was present in 37% of the population. At baseline, malnutrition assessed by SGA was the only factor independently (and negatively) associated with all four measures of HRQoL. No single factor was independently associated with decrease in all measures of HRQoL over 1 year. However, prevalence/development of malnutrition over one year was an independent predictor of 1-year decrease in EQ5D HSS and 1-year decrease in fat intake independently predicted the 1-year decline in SF-36 MCS and PCS, and EQ5D VAS. These findings strengthen the importance of monitoring for malnutrition and providing nutritional advice to all persons on dialysis. Future studies are needed to evaluate the impact of nutritional interventions on HRQoL and other long-term outcomes

The association of nutritional factors and skin autofluorescence in persons receiving hemodialysis

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycemia, oxidative stress and systemic inflammation. AGEs are also formed in food during cooking. On the other hand, malnutrition may contribute to AGE formation through its association with oxidative stress and inflammation. AGE accumulation can be measured by skin autofluorescence (SAF) and elevated SAF is independently associated with higher mortality on hemodialysis (HD). We aimed to investigate associations between SAF, dietary AGE intake and markers of malnutrition in persons receiving HD. Design and setting: single center cross-sectional study. Subjects: 120 participants on HD dialyzing at least three times per week for 3-4 hours. Main outcome measures: SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. Subjective Global Assessment was performed to evaluate nutritional status. Results: SAF was higher in malnourished participants and correlated negatively with serum albumin and cholesterol, HGS and energy, protein and fat intake and positively with C reactive protein and chronological age; SAF did not correlate with dietary AGE intake. Multivariable linear regression analysis showed that diabetes, smoking, serum albumin, HGS, protein intake and dialysis vintage were independent predictors of increased SAF. Conclusions: Markers of malnutrition were more important determinants of increased SAF than high dietary AGE intake in this HD population. Nutritional interventions aiming to reduce SAF by correcting malnutrition should therefore be investigated. The observed association between higher SAF and malnutrition may in part explain the previously reported association between higher SAF and mortality on HD

Observation of Nonspreading Wave Packets in an Imaginary Potential

We propose and experimentally demonstrate a method to prepare a nonspreading atomic wave packet. Our technique relies on a spatially modulated absorption constantly chiseling away from an initially broad de Broglie wave. The resulting contraction is balanced by dispersion due to Heisenberg's uncertainty principle. This quantum evolution results in the formation of a nonspreading wave packet of Gaussian form with a spatially quadratic phase. Experimentally, we confirm these predictions by observing the evolution of the momentum distribution. Moreover, by employing interferometric techniques, we measure the predicted quadratic phase across the wave packet. Nonspreading wave packets of this kind also exist in two space dimensions and we can control their amplitude and phase using optical elements.Comment: 4 figure

Light-Controlled Affinity Purification of Protein Complexes Exemplified by the Resting ZAP70 Interactome

Multiprotein complexes control the behavior of cells, such as of lymphocytes of the immune system. Methods to affinity purify protein complexes and to determine their interactome by mass spectrometry are thus widely used. One drawback of these methods is the presence of false positives. In fact, the elution of the protein of interest (POI) is achieved by changing the biochemical properties of the buffer, so that unspecifically bound proteins (the false positives) may also elute. Here, we developed an optogenetics-derived and light-controlled affinity purification method based on the light-regulated reversible protein interaction between phytochrome B (PhyB) and its phytochrome interacting factor 6 (PIF6). We engineered a truncated variant of PIF6 comprising only 22 amino acids that can be genetically fused to the POI as an affinity tag. Thereby the POI can be purified with PhyB-functionalized resin material using 660 nm light for binding and washing, and 740 nm light for elution. Far-red light-induced elution is effective but very mild as the same buffer is used for the wash and elution. As proof-of-concept, we expressed PIF-tagged variants of the tyrosine kinase ZAP70 in ZAP70-deficient Jurkat T cells, purified ZAP70 and associating proteins using our light-controlled system, and identified the interaction partners by quantitative mass spectrometry. Using unstimulated T cells, we were able to detect the known interaction partners, and could filter out all other proteins