Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression.

Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter. It is currently unknown if the rs2289669 locus is a cis-eQTL, which would validate its role as predictor of metformin efficacy. We looked at association between common genetic variants in the SLC47A1 gene region and HbA1c reduction after metformin treatment using locus-wise meta-analysis from the MetGen consortium. CRISPR-Cas9 was applied to perform allele editing of, or genomic deletion around, rs2289669 and of the closely linked rs8065082 in HepG2 cells. The genome-edited cells were evaluated for SLC47A1 expression and splicing. None of the common variants including rs2289669 showed significant association with metformin response. Genomic editing of either rs2289669 or rs8065082 did not alter SLC47A1 expression or splicing. Experimental and in silico analyses show that the rs2289669-containing haploblock does not appear to carry genetic variants that could explain its previously reported association with metformin efficacy.

The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial.

BACKGROUND: Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. METHODS: We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). RESULTS: Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). CONCLUSIONS: This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03020186.

Preliminary feasibility of animated video education designed to empower patients' referral to kidney transplantation.

BACKGROUND: Referral for kidney transplantation is influenced by patient education; digital technologies can enhance broad information accessibility. This single-group study tested the feasibility and acceptability of patient-centered self-directed educational animated videos to improve mediators of kidney transplant referral. METHODS: Community-based adults with chronic kidney disease stage ≥4 invited from a clinical registry or self-responding to flyers viewed eight sequential videos (19:36 min total duration) remotely on their own device. Change in kidney transplant knowledge, concerns, and confidence talking about kidney transplantation to doctors was assessed with self-report surveys before and immediately after viewing. Program feedback was assessed by survey and self-selected exit interview. RESULTS: Viewers of the video set (n = 50) demonstrated increases in mean kidney transplantation knowledge by +22%, confidence discussing with their doctor by +6%, and reductions in concerns by -2%. Knowledge results were consistent across age, race, and literacy level. Over 90% indicated positive ratings on understanding, engaging, and helpfulness. In post-study interviews viewers indicated the videos promoted confidence in obtaining a kidney transplant and none reported that the 19-min duration of the home education was too long. CONCLUSION: The animated video education is promising to improve diverse individuals' knowledge, concerns, and communication confidence about kidney transplantation and is highly acceptable.

Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance.

OBJECTIVE: Human white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism. DESIGN: Mesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR. RESULTS: While mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels. CONCLUSION: Multi-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.

How the Covid-19 pandemic has drawn attention to the issue of active mobility and co-benefits in Latin American cities.

The Covid-19 pandemic has brought to the fore many issues that will impact public health for years to come -one such impact is on the nexus between transportation and health. Promoting safe, active transport is an activity that has many physical and mental health benefits. During lockdowns, many cities in Latin America imposed infrastructural and legislative changes in order to abide with public health and social mea-sures to reduce virus spread. These ranged from additional bike lanes to reduced speed limits or incentives to purchase bicycles. These cities showed reduced motorized transport, improved air quality and increased active transport, all of which have multiple health and equity benefits. As countries "build back better", promoting active transport offers the most value for investment and improves health and well-being while continuing to offer social distancing. Quantified case studies are needed to have a more comprehensive under-standing of the impact of active transport in various contexts.

Effects of lifestyle interventions on epigenetic signatures of liver fat: Central randomized controlled trial.

BACKGROUND AND AIMS: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. METHODS: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. RESULTS: At baseline, participants (92% men; body mass index = 30.2 kg/m2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P < .05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P = .04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P < .05 for all, PA-vs. PA+). CONCLUSIONS: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions.

Video education to facilitate patient outreach about living kidney donation: A proof of concept.

BACKGROUND: Increasing living-donor kidney transplantation (LDKT) requires education of transplant candidates and their social network. This pre-post study tested the feasibility and acceptability of KidneyTIME, an intervention which leverages LDKT video-based educational content designed for sharing. METHODS: Adult kidney candidates undergoing transplant evaluation/re-evaluation and their caregivers at a single transplant center viewed different sets of KidneyTIME videos prior to evaluation. Change in LDKT knowledge, self-efficacy, and concerns was assessed before and immediately after exposure and 3 weeks later. Also assessed were post-exposure program feedback, online use, and living donor (LD) inquiry. RESULTS: A total of 82 candidates and 79 caregivers participated. Viewers of KidneyTIME demonstrated increases in mean LDKT knowledge by +71% and communication self-efficacy by +48%, and reductions in concerns by -21%. The intervention was received positively, with over 95% of participants agreeing that the videos were understandable, credible, and engaging. By 3 weeks follow-up, 58% had viewed it again, 63% of family clusters had shared it, and 100% would recommend the program to a friend. Time to LD inquiry was similar to historic controls. CONCLUSION: KidneyTime improved facilitators of LDKT, was rated as highly acceptable, and was highly shared, but did not impact LD inquiry during the COVID-19 pandemic.

Development of the living donation and kidney transplantation information made easy (KidneyTIME) educational animations.

BACKGROUND: Current web-based educational approaches about living kidney donation (LKD) are complex, lengthy, and/or text-laden, which may impair accurate interpretation of information, thereby limiting kidney transplant access. PURPOSE: This paper describes the process of developing animation-based LKD education designed to be suitable for and acceptable to kidney transplant candidates and their support networks. METHODS: Based on formative work, early animation prototypes were designed by a transplant surgeon and a health communication expert. In qualitative focus groups and individual interviews, animation prototypes were shown to 46 kidney transplant recipients, 28 kidney transplant candidates, 32 previous or potential kidney donors, 10 caregivers, 32 transplant providers, 24 dialysis providers, and 4 cultural and community advisors for their input regarding animation suitability, acceptability, and potential usability/feasibility. Viewer feedback was used to iteratively refine the animations. Animation design to facilitate adult learning was guided by elaboration theory, Bandura's self-efficacy theory, and Mayer's cognitive theory of multimedia learning. RESULTS: KidneyTIME currently consists of 12 animations about LKD process, benefits, and risks. CONCLUSIONS: Patients/friends/family members, experts, and stakeholders provided valuable feedback to the research team that was integrated into the development of KidneyTIME with the goal of enhancing suitability, acceptability, engagement, usability, and feasibility of dissemination.

Is it disgusting or am I just easily disgusted? The relation between situational disgust, dispositional disgust, and colonoscopy intentions.

OBJECTIVE: While early detection is an effective way to reduce mortality from colorectal cancer, screening rates are low. An underlying factor in screening completion failure may be experiences of disgust when learning about screening and/or dispositional disgust. METHOD: Participants recruited via Amazon MTurk (N = 296) read information about colonoscopy and completed an online survey assessing both dispositional forms of disgust (i.e. trait disgust and disgust sensitivity) and situational forms, including state disgust and disgust associated with colonoscopy. Participants reported intentions to discuss colonoscopy with a provider and to prepare for and complete screening. RESULTS: Greater state disgust and the degree to which one associated disgust with colonoscopy predicted lower screening, preparation and provider discussion intentions. By contrast, neither trait disgust nor disgust sensitivity was associated with intentions. Both disgust sensitivity and trait disgust moderated the state disgust to intentions relation. CONCLUSIONS: This is one of few investigations of disgust examining the relation between specific types and colonoscopy intentions. Screening uptake may be improved by identifying specific components of disgust that have an effect on colonoscopy intentions. Future work focusing on the interplay between different disgust mechanisms as they relate to colonoscopy behaviour is important for intervention development.

#BlackBreastsMatter: Process Evaluation of Recruitment and Engagement of Pregnant African American Women for a Social Media Intervention Study to Increase Breastfeeding.

BACKGROUND: In the United States, there are lower rates of breastfeeding among African American mothers, particularly those who are younger women. Recent epidemiological studies have shown a strong association of more aggressive types of breast cancer (estrogen receptor negative) among African American women, with a higher risk in African American women who did not breastfeed their children. OBJECTIVE: This study aims to describe the process evaluation of recruitment and educational strategies to engage pregnant African American participants for a pilot study designed to determine whether social media messaging about breast cancer risk reduction through breastfeeding may positively influence breastfeeding rates. METHODS: This pilot study is conducted in collaboration with a local Women, Infants, and Children (WIC) organization and hospital and prenatal clinics of a local health care network. To engage African American women to enroll in the study, several methods and monitoring processes were explored, including WIC electronic text-based messages sent out to all phones of current WIC recipients (referred to as e-blasts); keyword responses to texts from flyers and posters in local community-based organizations, hospitals, and prenatal clinics; keyword responses using electronic links posted in established Facebook groups; and snowball recruitment of other pregnant women by current participants through Facebook. Once enrolled, participants were randomized to 2 study conditions: (1) an intervention group receiving messages about breast cancer risk reduction and breastfeeding or (2) a control group receiving breastfeeding-only messages. Data were obtained through electronic monitoring, SurveyMonkey, qualitative responses on Facebook, focus groups, and interviews. RESULTS: More than 3000 text messages were sent and received through WIC e-blasts and keyword responses from flyers. A total of 472 women were recruited through WIC e-blast, and 161 responded to flyers and contacts through the local health care network, community-based organizations, Facebook, and friend referrals. A total of 633 women were assessed for eligibility to participate in the study. A total of 288 pregnant African American women were enrolled, consented, and completed presurvey assessments (102.8% of the goal), and 22 participants attended focus groups or interviews reporting on their experiences with Facebook and the educational messages. CONCLUSIONS: This process evaluation suggests that using electronic, smartphone apps with social media holds promise for both recruitment and conduct of health education intervention studies for pregnant African American women. Providing messaging and resources through social media to reinforce and educate women about breastfeeding and potentially provide lactation support is intriguing. Convenience (for researchers and participants) is an attribute of social media for this demographic of women and worthy of further research as an educational tool. TRIAL REGISTRATION: ClinicalTrials.gov NCT03680235; https://clinicaltrials.gov/ct2/show/NCT03680235.

The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: the GLACIER Study.

BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.

DNA methylation of SSPN is linked to adipose tissue distribution and glucose metabolism.

DNA methylation is a crucial epigenetic mechanism in obesity and fat distribution. We explored the Sarcospan ( SSPN) gene locus by using genome-wide data sets comprising methylation and expression data, pyrosequencing analysis in the promoter region, and genetic analysis of an SNP variant rs718314, which was previously reported to associate with waist-to-hip ratio. We found that DNA methylation influences several clinical variables related to fat distribution and glucose metabolism, while SSPN mRNA levels showed directionally opposite effects on these traits. Complete DNA methylation of the SSPN promoter construct suppressed the gene expression of firefly luciferase in MCF7 cells. Moreover, rs718314 was associated with waist and with DNA methylation at CpG sites. Our data strongly support the role of the SSPN locus in body fat composition and glucose homeostasis, and suggest that this is most likely the result of changes in DNA methylation of SSPN in adipose tissue.-Keller, M., Klös, M., Rohde, K., Krüger, J., Kurze, T., Dietrich, A., Schön, M. R., Gärtner, D., Lohmann, T., Dreßler, M., Stumvoll, M., Blüher, M., Kovacs, P., Böttcher, Y. DNA methylation of SSPN is linked to adipose tissue distribution and glucose metabolism.

Development and preliminary evaluation of ilearnKAS: An animated video about kidney allocation to support transplant decision-making.

BACKGROUND: We aimed to develop and feasibility test an educational video culturally targeted to African American (AA) patients regarding kidney allocation. METHODS: We iteratively refined an animated video for AAs with multiple stakeholder input and conducted a one-group, pre-post study with 50 kidney transplant candidates to assess video feasibility and acceptability. A mixed population was chosen to obtain race-specific acceptability data and efficacy estimates for a larger study. RESULTS: Median participant age was 56 years, and 50% were AA. Comparing pre-post video scores, large knowledge effect sizes were found for the cohort (r = 0.7) and in the context of AA race (r = 0.8), low health literacy (r = 0.6), low educational achievement (r = 0.7), age >55 years (r = 0.6), dialysis vintage ≥1 year (r = 0.8), low income (r = 0.7) and low technology access (r = 0.8). Over 87% of participants provided positive ratings on each of the seven acceptability items. The frequency of positive responses increased pre-post video for kidney allocation understanding (78% vs 94%, P = 0.008), decisional self-efficacy (64% vs 88%, P < 0.001) and belief in fairness (76% vs 90%, P = 0.02). CONCLUSIONS: In collaboration with key stakeholders, a culturally targeted educational video was developed that was well received. Results are promising to impact kidney allocation knowledge among AA and non-AA kidney transplant candidates.

Genetic variants in AKR1B10 associate with human eating behavior.

BACKGROUND: The human Aldoketoreductase 1B10 gene (AKR1B10) encodes one of the enzymes belonging to the family of aldoketoreductases and may be involved in detoxification of nutrients during digestion. Further, AKR1B10 mRNA (messenger ribonucleic acid) expression was diminished in brain regions potentially involved in the regulation of eating behavior in rats which are more sensitive to cocaine and alcohol. We hypothesized that the human AKR1B10 gene may also play a role in the regulation of human eating behavior. RESULTS: We investigated the effects of 5 genetic variants of AKR1B10 on human eating behavior among 548 subjects from a German self-contained population, the Sorbs, and in 350 subjects from another independent German cohort. Among the Sorbs, we observed nominal associations with disinhibition at the 5' untranslated region (5' UTR) variant rs10232478 and the intragenic variants rs1834150 and rs782881 (all P ≤ 0.05). Further, we detected a relationship of rs1834150 and rs782881 with waist, smoking consumption (rs782881) and coffee consumption (rs1834150) (all P ≤ 0.05). Albeit non-significant, replication analyses revealed similar effect directions for disinhibition at rs1834150 (combined P = 0.0096). Moreover, in the replication cohort we found rs1834150 related to increased restraint scores with a similar direction as in the Sorbs (combined P = 0.0072). CONCLUSION: Our data suggest that genetic variants in the AKR1B10 locus may influence human eating behavior.

Global DNA methylation levels in human adipose tissue are related to fat distribution and glucose homeostasis.

AIMS/HYPOTHESIS: Epigenetic alterations may influence the metabolic pathways involved in human obesity. We hypothesised that global DNA methylation levels in adipose tissue might be associated with obesity and related phenotypes. METHODS: We measured global DNA methylation levels in paired samples of subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from 51 individuals, and in leucocytes from 559 Sorbs, a population from Germany, using LUminometric Methylation Assay (LUMA). To further investigate the underlying mechanisms of the observed associations, we measured global methylation levels in 3T3-L1 adipocytes exposed to glucose, insulin and lipids. RESULTS: Global methylation levels (±SD) were significantly higher in OVAT (74.27% ± 2.2%) compared with SAT (71.97% ± 2.4%; paired t test, p < 1 × 10(-9)). Furthermore, global methylation levels in SAT were positive correlates of measures of fat distribution (waist measurement, WHR) and glucose homeostasis (HbA1c) (all p < 0.015 after accounting for multiple testing and covariates). Global methylation levels in the German Sorb cohort were associated with glucose homeostasis, but this association did not withstand adjustment for covariates. Exposure of 3T3-L1 adipocytes to insulin, palmitate and glucose decreased global methylation levels 1 h after treatment relative to controls. CONCLUSIONS/INTERPRETATION: Our data suggest that the variability in global methylation in adipose tissue might be related to alterations in glucose metabolism.

Newspaper framing of motor vehicle crashes and road safety in Argentina.

The media plays a key role in shaping the public's perception of road safety. This study analyzes the newspaper coverage and framing of motor vehicle crashes (MVCs) and road safety in Argentina, South America. The content of 304 articles published by 15 newspapers in November 2020 was reviewed. The results show that episodically framed news stories (focused on a single event or incident) prevail over thematically framed articles. MVCs are presented primarily as 'police' events and tend to receive more coverage when fatalities are involved. There is limited information provided on contextual and risk factors, and road safety advice is rarely included. Speeding, infrastructure, alcohol and other human-related variables are the most cited risk factors. Very few articles mention the use of protective devices (seat-belt, helmet and child restraint system). Although motorcyclists represent 40% of RTC deaths in Argentina, only 20% of the news coverage was about them. News coverage was quite similar in national and regional newspapers. There is an opportunity for the media to help build a better road safety culture, but significant changes in news framing are required. Practical recommendations for editors, journalists and road safety practitioners are provided.

Preliminary Evaluation of 2 Patient-Centered Educational Animations About Kidney Transplant Complications.

BACKGROUND Fear of kidney transplant complications and incomplete information can lower transplant acceptance and preparedness. Our group developed 2 patient-centered educational animated videos on common kidney transplant complications to complement a previously developed video-based curriculum intended to promote kidney transplant access. MATERIAL AND METHODS We preliminarily evaluated the 2 animated educational videos at a single center using mixed methods. We conducted a before-and-after single group study with 22 patients after kidney transplantation to measure the videos' acceptability and feasibility to improve patient knowledge, understanding, and concerns of kidney transplant complications. Concurrently, we individually interviewed 12 patients before kidney transplantation about their perceptions of the 2 videos and analyzed the data thematically. RESULTS Knowledge of kidney transplant complications increased 10% (7.82 to 8.59, P=0.002) from before to after video viewing. Large effect size increases for knowledge were found for different strata of age, race, and health literacy. The mean total score for perceived understanding of kidney transplant complications increased after video exposure by 7% (mean 2.48 to 2.66, P=0.184). There was no change in kidney transplant concern scores from before to after video viewing (mean 1.70 to 1.70, P=1.00). After video viewing, all patients reported positive ratings on comfort watching, understanding, and engaging. Three themes of patient perceptions emerged: (1) messages received as intended, (2) felt informed, and (3) scared but not deterred. CONCLUSIONS Two animated educational videos about kidney transplant complications were well received and promise to positively impact individuals' knowledge and understanding, without raising excessive concerns.

Blood methylation pattern reflects epigenetic remodelling in adipose tissue after bariatric surgery.

BACKGROUND: Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood. METHODS: Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N = 6 female) with severe obesity pre- and post-surgery. FINDINGS: The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from -11.5 to 10.8%; OVAT: 14,632 DMRs from -13.7 to 12.8%) than in blood (9267 DMRs from -8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49 regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery. INTERPRETATION: Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors AT's inflammatory state post-bariatric surgery. FUNDING: The funding sources are listed in the Acknowledgments section.

THOC5: a novel gene involved in HDL-cholesterol metabolism.

Although numerous genes are known to regulate serum lipid traits, identified variants explain only a small proportion of the expected heritability. We intended to identify further genetic variants associated with lipid phenotypes in a self-contained population of Sorbs in Germany. We performed a genome-wide association study (GWAS) on LDL-cholesterol, HDL-cholesterol (HDL-C), and triglyceride (TG) levels in 839 Sorbs. All single-nucleotide polymorphisms with a P value <0.01 were subjected to a meta-analysis, including an independent Swedish cohort (Diabetes Genetics Initiative; n = ∼3,100). Novel association signals with the strongest effects were subjected to replication studies in an additional German cohort (Berlin, n = 2,031). In the initial GWAS in the Sorbs, we identified 14 loci associated with lipid phenotypes reaching P values <10⁻5 and confirmed significant effects for 18 previously reported loci. The combined meta-analysis of the three study cohorts (n(HDL) = 6041; n(LDL) = 5,995; n(TG) = 6,087) revealed a novel association for a variant in THOC5 (rs8135828) with serum HDL-C levels (P = 1.78 × 10⁻7; Z-score = -5.221). Consistently, the variant was also associated with circulating APOA1 levels in Sorbs. The small interfering RNA-mediated mRNA silencing of THOC5 in HepG2 cells resulted in lower mRNA levels of APOA1, SCARB1, and ABCG8 (all P < 0.05). We propose THOC5 to be a novel gene involved in the regulation of serum HDL-C levels.