50 jaar Studentenvereniging voor Internationale Betrekkingen (SIB)

"Samenwerking in VN-verband: United for a better world." Met dit congres heeft de Studenten- en Jongerenvereniging voor Internationale Betrekkingen (SIB) op 24 maart jongstleden haar VN-campagne gestart. De SIB staat in de maanden maart tot en met november stil bij de rol en het nut van de Verenigde Naties. Dit wordt aan de hand van actuele thema's in lezingen, fora, excursies en twee landelijke congressen uitgewerkt. Met een kritisch oog wordt de geschiedenis en toekomst van de grootste internationale gouvernementele organisatie aan de orde gesteld. Op 3 november zal de VN-campagne worden afgesloten met een congres over Verdraagzaamheid in het Vredespaleis in Den Haag

Quantification of free water transport in peritoneal dialysis

Quantification of free water transport in peritoneal dialysis.BackgroundIn peritoneal dialysis (PD) total net ultrafiltration (NUF) is dependent on transport through small pores and through water channels in the peritoneum. These channels are impermeable to solutes, and therefore, crystalloid osmotic-induced free water transport occurs through them. Several indirect methods to assess free water transport have been suggested. The difference in NUF between a 3.86% and a 1.36% solution gives a rough indication, but is very time consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the initial phase of a 3.86% exchange is another way to estimate free water transport. In the present study, a method was applied to calculate free water transport by calculating sodium-associated water transport in one single 3.86% glucose dwell.MethodsForty PD patients underwent one standard peritoneal permeability analysis (SPA) with a 1.36% glucose solution, and another with a 3.86% glucose solution. At different time points intraperitoneal volume and sodium concentration were assessed. This made it possible to calculate total sodium transport. By subtracting this transport (which must have occurred through the small pores) from the total fluid transport, free water transport remained. These results were compared with the other methods to estimate free water transport.ResultsFor the 1.36% glucose dwell, total transcapillary ultrafiltration in the first hour (TCUF0-60) was 164 mL, transport through the small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86% glucose solution, total TCUF0-60 was 404 mL, transport through the small pores was 269 mL, and free water transport was 135 mL (34%). The contribution of free water transport in the first minute (TCUF0-1) was 39% of the total fluid transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF <400 mL after 4 hours). For these patients the contribution of free water to TCUF0-1 was significantly lower than for those with normal ultrafiltration (20% vs. 48%, P < 0.05). A strong correlation was present between free water transport as a percentage of total fluid transport and the maximum dip in D/P sodium (r = 0.84). The correlation was not significant with the difference in net ultrafiltration of 3.86% and 1.36% solutions (r = 0.24, P = 0.3).ConclusionThe method applied here is the first direct quantification of free water transport, calculated from a single standard peritoneal function test. It offers a quick possibility to evaluate patients suffering from ultrafiltration failure. In these patients free water transport was impaired, but the origin of this impairment is still to be determined

Leptin concentration and risk of impaired physical function in older adults: the Seniors-ENRICA cohort

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Age and Ageing following peer review. The version of record Alberto Lana, Ellen Struijk, Pilar Guallar-Castillón, Jose María Martín-Moreno, Fernando Rodríguez Artalejo, Esther Lopez-Garcia; Leptin concentration and risk of impaired physical function in older adults: the Seniors-ENRICA cohort. Age Ageing 45.6 (2016): 819-826 is available online at: http://dx.doi.org/ 10.1093/ageing/afw142Leptin resistance, which may develop during the aging process, stimulates the production of proinflammatory cytokines and insulin resistance that could impair the muscle function. However, the role of leptin on physical functioning among older adults has not yet been elucidated. Objective: To examine the association between serum leptin levels and physical function impairment in older adults. Design and setting: Prospective study of 1,556 individuals aged ≥60 years from the Seniors-ENRICA cohort, who were free of physical function limitation at baseline. Main outcome measure: Serum leptin was measured in 2008-2010, and incident functional limitation was assessed through 2012. Self-reported limitations in agility and mobility were assessed with the Rosow and Breslau scale, limitation in the lower extremity function was measured with the Short Physical Performance Battery, and impairment in the overall physical performance with the physical component summary of the SF-12. Results: After adjustment for potential confounders, and compared to individuals in the lowest quartile of leptin concentration, those in the highest quartile showed increased risk of impaired physical function; the odds ratio (95% confidence interval) and p-trend was: 1.95 (1.11-3.43), p=0.006 for self-reported impaired mobility; 1.76 (1.08-2.87), p=0.02 for self-reported impaired agility; 1.48 (1.02-2.15), p=0.04 for limitation in the lower extremity function; and 1.97 (1.20-3.22), p=0.01 for decreased overall physical performance. These associations were only modestly explained by C-reactive protein and insulin resistance. Moreover, the associations held across groups with varying health status and were independent of estimated total body fat. Conclusions: Higher leptin concentration was associated with increased risk of impaired physical function. Preserving metabolic function during the old age could help delaying physical function declineThis work was supported by FIS grants 12/1166 and 13/0288 (Instituto de Salud Carlos III, State Secretary of R+D+I, and FEDER/FSE), the CIBERESP, the FRAILOMIC Initiative (FP7-HEALTH-2012-Proposal no. 305483-2) and the ATHLOS project (EU H2020- Project ID: 635316

Augmenting solute clearance in peritoneal dialysis

Augmenting solute clearance in peritoneal dialysis.BackgroundThe removal of low molecular weight solutes by peritoneal dialysis is less than by hemodialysis. The targets for Kt/Vurea and creatinine clearance formulated in the Dialysis Outcome Quality Initiative are unlikely to be achieved in a substantial portion of peritoneal dialysis patients. Possibilities to increase small solute clearances have therefore been subject to many investigations.MethodsA review of the literature and of recent new data on determinants of solute removal, such as residual renal function, the role of drained dialysate volume and manipulation of the diffusive capacity of the peritoneum are presented.ResultsThe contribution of residual GFR is more important for the clearance of creatinine than for Kt/Vurea. It is even more important for the removal of organic acids that are removed from the body by tubular secretion. High dosages of furosemide increase the urinary volume and the fractional Na+ excretion, but have no effect on the magnitude of residual GFR, renal creatinine clearance, renal urea clearance, and peritoneal transport characteristics. The drained dialysate volume per day is the main determinant of the peritoneal removal of urea. Its effect decreases the higher the molecular weight of a solute. It can be augmented by using large instillation volumes, by the application of more exchanges, and by increasing peritoneal ultrafiltration. A large exchange volume is especially effective in patients with an average transport state, but in those with high solute transport rates, Kt/Vurea is especially influenced by the number of exchanges. Possibilities to increase ultrafiltration are discussed. The diffusive capacity of the peritoneum can be augmented by using low dosages of intraperitoneally administered nitroprusside. This increases solute transport most markedly when it is applied in combination with icodextrin as osmotic agent.ConclusionsSmall solutes clearances cannot be increased by furosemide. Increasing the instilled volume of dialysis fluid and the number of exchanges both affect solute clearance. Studies are necessary on long-term effects of manipulation of the peritoneal membrane with nitroprusside

Comparison of Longitudinal Membrane Function in Peritoneal Dialysis Patients According to Dialysis Fluid Biocompatibility

Introduction: Preservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality. Methods: We conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined. Results: One hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixtyseven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (-28.0 ml/min per year; 95% CI: -60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (-291 ml/min per year; 95% CI: -550 to -32) while this was absent in biocompatible treatment. Conclusion: Despite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions. (C) 2020 International Society of Nephrology. Published by Elsevier Inc

Comparison of DNA methylation patterns of parentally imprinted genes in placenta derived from IVF conceptions in two different culture media

Study question: Is there a difference in DNA methylation status of imprinted genes in placentas derived from IVF conceptions where embryo culture was performed in human tubal fluid (HTF) versus G5 culture medium? Summary answer: We found no statistically significant differences in the mean DNA methylation status of differentially methylated regions (DMRs) associated with parentally imprinted genes in placentas derived from IVF conceptions cultured in HTF versus G5 culture medium. What is known already: Animal studies indicate that the embryo culture environment affects the DNA methylation status of the embryo. In humans, birthweight is known to be affected by the type of embryo culture medium used. The effect of embryo culture media on pregnancy, birth and child development may thus be mediated by differential methylation of parentally imprinted genes in the placenta. Study design, size, duration: To identify differential DNA methylation of imprinted genes in human placenta derived from IVF conceptions exposed to HTF or G5 embryo culture medium, placenta samples (n = 43 for HTF, n = 54 for G5) were collected between 2010 and 2012 s as part of a multi-center randomized controlled trial in the Netherlands comparing these embryo culture media. Placenta samples from 69 naturally conceived (NC) live births were collected during 2008-2013 in the Netherlands as reference material. Participants/materials, setting, methods: To identify differential DNA methylation of imprinted genes, we opted for an amplicon-based sequencing strategy on an Illumina MiSeq sequencing platform. DNA was isolated and 34 DMRs associated with well-defined parentally imprinted genes were amplified in a two-step PCR before sequencing using MiSeq technology. Sequencing data were analyzed in a multivariate fashion to eliminate possible confounding effects. Main results and the role of chance: We found no statistically significant differences in the mean DNA methylation status of any of the imprinted DMRs in placentas derived from IVF conceptions cultured in HTF or G5 culture medium. We also did not observe any differences in the mean methylation status per amplicon nor in the variance in methylation per amplicon between the two culture medium groups. A separate surrogate variable analysis also demonstrated that the IVF culture medium was not associated with the DNA methylation status of these DMRs. The mean methylation level and variance per CpG was equal between HTF and G5 placenta. Additional comparison of DNA methylation status of NC placenta samples revealed no statistically significant differences in mean amplicon and CpG methylation between G5, HTF and NC placenta; however, the number of placenta samples exhibiting outlier methylation levels was higher in IVF placenta compared to NC (P < 0.00001). Also, we were able to identify 37 CpG sites that uniquely displayed outlier methylation in G5 placentas and 32 CpG sites that uniquely displayed outlier methylation in HTF. In 8/37 (G5) and 4/32 (HTF) unique outliers CpGs, a medium-specific unique outlier could be directly correlated to outlier methylation of the entire amplicon. Limitations, reasons for caution: Due to practical reasons, not all placentas were collected during the trial, and we collected the placentas from natural conceptions from a different cohort, potentially creating bias. We limited ourselves to the DNA methylation status of 34 imprinted DMRs, and we studied only the placenta and no other embryo-derived tissues. Wider implications of the findings: It has often been postulated, but has yet to be rigorously tested, that imprinting mediates the effects of embryo culture conditions on pregnancy, birth and child development in humans. Since we did not detect any statistically significant effects of embryo culture conditions on methylation status of imprinted genes in the placenta, this suggests that other unexplored mechanisms may underlie these effects. The biological and clinical relevance of detected outliers with respect to methylation levels of CpGs and DMR require additional analysis in a larger sample size as well. Given the importance and the growing number of children born through IVF, research into these molecular mechanisms is urgently needed. Study funding/competing interest(s): This study was funded by the March of Dimes grant number #6-FY13-153. The authors have no conflicts of interest. Trial registration number: Placental biopsies were obtained under Netherlands Trial Registry number 1979 and 1298

Comparison of Different Methods for Estimating Cardiac Timings: A Comprehensive Multimodal Echocardiography Investigation

Cardiac time intervals are important hemodynamic indices and provide information about left ventricular performance. Phonocardiography (PCG), impedance cardiography (ICG), and recently, seismocardiography (SCG) have been unobtrusive methods of choice for detection of cardiac time intervals and have potentials to be integrated into wearable devices. The main purpose of this study was to investigate the accuracy and precision of beat-to-beat extraction of cardiac timings from the PCG, ICG and SCG recordings in comparison to multimodal echocardiography (Doppler, TDI, and M-mode) as the gold clinical standard. Recordings were obtained from 86 healthy adults and in total 2,120 cardiac cycles were analyzed. For estimation of the pre-ejection period (PEP), 43% of ICG annotations fell in the corresponding echocardiography ranges while this was 86% for SCG. For estimation of the total systolic time (TST), these numbers were 43, 80, and 90% for ICG, PCG, and SCG, respectively. In summary, SCG and PCG signals provided an acceptable accuracy and precision in estimating cardiac timings, as compared to ICG