Outcomes of renal replacement therapy in boys with prune belly syndrome : findings from the ESPN/ERA-EDTA Registry

As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data. Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD). Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups. This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.Peer reviewe

Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole

AbstractThis study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH. All formulations remained amorphous at 25°C/60% RH. Only the MPSDD formulation containing HPMCAS-M and 3/7 (wt./wt.) FLU/OMS did not crystallize following 40°C/75% RH exposure. The OMS and MPSDD formulations contained the lowest and highest amount of hydrolyzed degradant, respectively. All formulations were dosed to rats at 20 mg/kg in suspension. One FLU/OMS formulation was also dosed as a capsule blend. Plasma concentration profiles were determined following a single dose. In vivo findings show that the OMS capsule and suspension resulted in the overall highest area under the curve and Cmax values, respectively. These results cross-evaluate various amorphous formulations and provide a link to enhanced biopharmaceutical performance

Specific plasma microRNAs are associated with CD4+ T-cell recovery during suppressive antiretroviral therapy for HIV-1

SUPPORTING INFORMATION: FILE S1: SUPPLEMENTAL DIGITAL CONTENTOBJECTIVE: This study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4þ T-cell recovery during the first year of ART. DESIGN: MicroRNAs were retrospectively measured in stored plasma samples from people with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry cohort and who had plasma viral-load less than 50 copies/ml after 12 months of ART. METHODS: First, the levels of 179 microRNAs were screened in a subset of participants from the lowest and highest tertiles of CD4þ T-cell recovery (DCD4) (N ¼ 12 each). Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile DCD4: n ¼ 61, highest tertile DCD4: n ¼ 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH to HIV-negative controls. RESULTS: Poor CD4þ T-cell recovery was associated with higher levels of hsa-miR-199a3p and hsa-miR-200c-3p before ART, and of hsa-miR-17-5p and hsa-miR-501-3p during ART. Signaling by VEGF and MET, and RNA polymerase II transcription pathways were identified as possible targets of hsa-miR-199a-3p, hsa-200c-3p, and hsamiR-17-5p. Compared with HIV-negative controls, we observed lower hsa-miR-326, hsa-miR-497-5p, and hsa-miR-501-3p levels before and during ART in all PWH, and higher hsa-miR-199a-3p and hsa-miR-200c-3p levels before ART in all PWH, and during ART in PWH with poor CD4þ T-cell recovery only. CONCLUSION: These findings add to the understanding of pathways involved in persistent HIV-induced immune dysregulation during suppressive ART.A Veni postdoc fellowship to R.L.H. through the Dutch Research Council (NWO) Talent Programme (91615036), and Gilead Sciences Netherlands through an unrestricted scientific grant.https://journals.lww.com/aidsonline/pages/default.aspxImmunologySDG-03:Good heatlh and well-bein

Transitions to food democracy through multilevel governance

status: publishe

Transitions to food democracy through multilevel governance

Food systems in Europe are largely unjust and not sustainable. Despite substantial negative consequences for individual health, the environment and public sector health and care services, large multi-national corporations continue to benefit from the way food systems are designed—perpetuating “Lose–Lose–Lose–Win” food systems that see these large corporations benefit at the expense of health, the environment and public sector finances. Transitioning to “Win–Win–Win–Win” food systems is challenging because of the heterogeneity, complexity and unpredictable nature of food systems—one-size fits-all solutions to correct imbalances and injustices cannot exist. To address these challenges, we propose the use of heuristics—solutions that can flexibly account for different contexts, preferences and needs. Within food systems, food democracy could be a heuristic solution that provides the processes and can form the basis for driving just transitions. However, ensuring that these transition processes are fair, equitable, sustainable and constructive, requires an approach that can be used across vertical and horizontal governance spheres to ensure the voices of key stakeholders across space, time and spheres of power are accounted for. In this manuscript we outline a new Horizon project, FEAST, that aims to use multilevel governance approaches across vertical and horizontal spheres of governance to realize constructive food democracy. We envisage this as a means to inform just processes that can be used to design and implement policies, in line with food democracy, to facilitate transitions to “Win–Win–Win–Win” food systems across Europe that makes it easy for every European to eat a healthy and sustainable diet

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Government Calling Revisited: A Survey-Experiment on the Moderating Role of Public Service Motivation in Assessing Employer Attractiveness

Employer attractiveness is an important variable for any organization. It is therefore not surprising that organizations try to control this facet when communicating recruitment messages for positions to be filled. This study aims to capture this process for public sector organizations, while looking at the role that a particular type of prosocial motivation – public service motivation: the motivation people have to contribute to society – plays in this process. To this end, a survey-experiment (N = 192) with prospective employees is carried out in which recruitment messages with three different value statements (public, private, neutral) are presented to the respondents. The effect of these message on both attractiveness and person–organization fit, as moderated by public service motivation, is tested. The results indicate that public service motivation indeed moderates the effect of these messages. However, the results do not fully corroborate the theoretical expectations. Therefore, additional exploratory analyses are performed in order to better understand the variables included in this process. This provides a direction for further research. Theoretical and practical implications are discussed

Exploring the functional mealtime associations of older adults through consumer segmentation and a means-end chain approach

Senior consumers are a rapidly growing and highly heterogeneous part of the world's population. This group does not always meet its recommended protein intake, which can negatively impact on their physical functioning and quality of life. To date, little is known about their motivations to consume protein-rich meals. In the current study, we therefore aim to identify consumer segments within the group of vital community-dwelling older adults on the basis of mealtime functionality (for example ‘I eat because I'm hungry’, or ‘I eat because it is cosy’). To this end, we first conducted an online survey to identify these functional mealtime expectations of older consumers (study I, n = 398, 158 males, mean age 65.8 (y) ± 5.9 (SD)). To obtain further insights regarding mealtime functionality and proteins/protein enrichment, laddering interviews were conducted with a subgroup of the segmentation study participants (study II, n = 40, 20 males, mean age 66.9 (y) ± 4.8 (SD)). The results of the online survey showed three consumer clusters: cosy socialisers, physical nutritioners, and thoughtless rewarders. Thoughtless rewarders tend to eat without having explicit thoughts about it, they eat for the reward, and score highest on environmental awareness. Both the segmentation and the in-depth interviews showed that, for the cosy socialisers, the cosiness and social function of a meal are important motivators, whereas for the physical nutritioners the focus is more on the health and nutrient aspects of a meal. For cosy socialisers, protein enrichment can best be achieved through addition of protein-rich ingredients, whereas, for physical nutritioners, addition of protein powder is preferred. These results provide practical guidelines for the development of protein-rich meals and communication strategies tailored to the needs of specific vital community-dwelling older subgroups.</p

Government Calling Revisited: A Survey-Experiment on the Moderating Role of Public Service Motivation in Assessing Employer Attractiveness

Employer attractiveness is an important variable for any organization. It is therefore not surprising that organizations try to control this facet when communicating recruitment messages for positions to be filled. This study aims to capture this process for public sector organizations, while looking at the role that a particular type of prosocial motivation – public service motivation: the motivation people have to contribute to society – plays in this process. To this end, a survey-experiment (N = 192) with prospective employees is carried out in which recruitment messages with three different value statements (public, private, neutral) are presented to the respondents. The effect of these message on both attractiveness and person–organization fit, as moderated by public service motivation, is tested. The results indicate that public service motivation indeed moderates the effect of these messages. However, the results do not fully corroborate the theoretical expectations. Therefore, additional exploratory analyses are performed in order to better understand the variables included in this process. This provides a direction for further research. Theoretical and practical implications are discussed

Self-reported food-evoked emotions of younger adults, older normosmic adults, and older hyposmic adults as measured using the PrEmo2 tool and the Affect Grid

Food-evoked emotions may provide relevant consumer insights, beyond liking alone. Previous research, using the EsSense25 method, showed that the food-evoked emotion profiles of adults vary along the two dimensions valence and arousal, whereas those as reported by seniors vary mainly in valence. However, it is unknown to what extent these findings can be replicated using other self-reported emotion measuring tools. This study therefore compared food-evoked emotion profiles of 71 younger adults (mean age 30.8 (years) ± 9.3 (SD)), 86 older normosmic adults (i.e. normal sense of smell, mean age 67.5 (years) ± 5.4 (SD)), and 70 older hyposmic adults (i.e. impaired sense of smell, mean age 68.2 (years) ± 5.9 (SD)). These groups evaluated three types of gingerbread and three types of chocolate using the self-reporting emotion measurement tools PrEmo2 tool and the Affect Grid. In line with previous observations, the self-reported emotion profiles differed between the age groups. The emotion profiles of younger adults varied for both methods along the dimensions valence and arousal, whereas, for the older groups, this valence/arousal differentiation was less clear. The effect of olfactory function was less pronounced, as the older adults with normal and impaired olfactory function had similar emotion profiles. For the PrEmo2 tool specifically, the older adults had generally lower scores for negative emotions compared to the younger adults. Hence, age should be considered an important factor when self-reported food-evoked emotions are being measured in order to develop food products targeted at specific consumer groups.</p