Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease.

This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10-10) and UC (P < 2 × 10-16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10-8) and UC (P = 1.04 × 10-4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10-6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis.

The runt-related transcription factor 3 (RUNX3) regulates the differentiation of monocytes and their response to inflammation. However, the transcriptomic context of RUNX3 expression in blood monocytes remains poorly understood. We aim to learn about RUNX3 from its relationships within transcriptomes of bulk CD14+ cells in adults. This study used immunomagnetically sorted CD14+ cell gene expression microarray data from the Multi-Ethnic Study of Atherosclerosis (MESA, n = 1202, GSE56047) and the Correlated Expression and Disease Association Research (CEDAR, n = 281, E-MTAB-6667) cohorts. The data were preprocessed, subjected to RUNX3-focused correlation analyses and random forest modeling, followed by the gene ontology analysis. Immunity-focused differential ratio analysis with intermediary inference (DRAIMI) was used to integrate the data with protein-protein interaction network. Correlation analysis of RUNX3 expression revealed the strongest positive association for EVL (rmean = 0.75, pFDR-MESA = 5.37 × 10-140, pFDR-CEDAR = 5.52 × 10-80), ARHGAP17 (rmean = 0.74, pFDR-MESA = 1.13 × 10-169, pFDR-CEDAR = 9.20 × 10-59), DNMT1 (rmean = 0.74, pFDR-MESA = 1.10 × 10-169, pFDR-CEDAR = 1.67 × 10-58), and CLEC16A (rmean = 0.72, pFDR-MESA = 3.51 × 10-154, pFDR-CEDAR = 2.27 × 10-55), while the top negative correlates were C2ORF76 (rmean = -0.57, pFDR-MESA = 8.70 × 10-94, pFDR-CEDAR = 1.31 × 10-25) and TBC1D7 (rmean = -0.55, pFDR-MESA = 1.36 × 10-69, pFDR-CEDAR = 7.81 × 10-30). The RUNX3-associated transcriptome signature was involved in mRNA metabolism, signal transduction, and the organization of cytoskeleton, chromosomes, and chromatin, which may all accompany mitosis. Transcriptomic context of RUNX3 expression in monocytes hints at its relationship with cell growth, shape maintenance, and aspects of the immune response, including tyrosine kinases.

Autoantibodies and Clinical Correlations in Polish Systemic Sclerosis Patients: A Cross-Sectional Study.

We evaluated the prevalence of systemic sclerosis (SSc)-related autoantibodies and their clinical significance and compared the sensitivity of two line immunoblot assays on a prospective study group of 96 Polish SSc patients (ACR-EULAR 2013 criteria) whose sera were assessed by indirect immunofluorescence (HEp-2 and monkey liver) and line immunoblot assays: ANA Profile 3 and Systemic Sclerosis Profile by EUROIMMUN (Lübeck, Germany). Organ involvement was evaluated according to the EUSTAR Minimal Essential Data Set. The following autoantibodies' prevalence was found: Scl-70 (36%), Ro-52 (28%), CENP-B (22%), CENP-A (20%), PM-Scl-75 (20%), PM-Scl-100 (14%), fibrillarin (7%), Th/To (7%), RNA polymerase III 11 kDa (5%), RNA polymerase III 155 kDa (3%), PDGFR (3%), NOR-90 (2%), and Ku (1%). Significant associations between the autoantibodies' presence and organ involvement were found: ATA (dcSSc > lcSSc, less prevalent muscle weakness), Ro-52 (gangrene, DLCO < 60), CENP-B and A (lcSSc > dcSSc, normal CK), CENP-B (rarer digital ulcers and joint contractures), PM-Scl-100 and 75 (PM/SSc overlap, CK increase, muscle weakness, muscle atrophy), PM-Scl-100 (dcSSc unlikely), PM-Scl-75 (lung fibrosis), fibrillarin (muscle atrophy, proteinuria, conduction blocks, palpitations), Th/To (proteinuria, arthritis, muscle weakness, and rarer esophageal symptoms), RNA Polymerase III 11 kDa (arterial hypertension, renal crisis), RNA polymerase III 155 kDa (renal crisis), and PDGFR (dcSSc, tendon friction rubs). Additionally, the Systemic Sclerosis Profile was significantly more sensitive in detecting SSc-related autoantibodies than ANA Profile 3 (p = 0.002). In conclusion, individual autoantibodies associated with specific characteristics of SSc.

Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis.

Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was -0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1-E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

Fat-Soluble Vitamins in Standard vs. Liposomal Form Enriched with Vitamin K2 in Cystic Fibrosis: A Randomized Multi-Center Trial.

BACKGROUND: We aimed to assess a liposomal fat-soluble vitamin formulation containing vitamin K2 with standard treatment in cystic fibrosis (CF). METHODS: A multi-center randomized controlled trial was carried out in 100 pancreatic-insufficient patients with CF. The liposomal formulation contained vitamin A as retinyl palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 µg). It was compared with the standard vitamin preparations in the closest possible doses (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively; no vitamin K2) over 3 months. RESULTS: Forty-two patients finished the trial in the liposomal and 49 in the control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m2, FEV1% 70% ± 30%). The main outcome was the change of vitamin status in the serum during the study (liposomal vs. standard): all-trans-retinol (+1.48 ± 95.9 vs. -43.1 ± 121.4 ng/mL, p = 0.054), 25-hydroxyvitamin D3 (+9.7 ± 13.4 vs. +2.0 ± 9.8 ng/mL, p = 0.004), α-tocopherol (+1.5 ± 2.5 vs. -0.2 ± 1.6 µg/mL, p < 0.001), %undercarboxylated osteocalcin (-17.2 ± 24.8% vs. -8.3 ± 18.5%, p = 0.061). The secondary outcome was the vitamin status at the trial end: all-trans-retinol (370.0 ± 116.5 vs. 323.1 ± 100.6 ng/mL, p = 0.045), 25-hydroxyvitamin D3 (43.2 ± 16.6 vs. 32.7 ± 11.5 ng/mL, p < 0.001), α-tocopherol (9.0 ± 3.1 vs. 7.7 ± 3.0 µg/mL, p = 0.037), %undercarboxylated osteocalcin (13.0 ± 11.2% vs. 22.7 ± 22.0%, p = 0.008). CONCLUSION: The liposomal fat-soluble vitamin supplement containing vitamin K2 was superior to the standard form in delivering vitamin D3 and E in pancreatic-insufficient patients with CF. The supplement was also more effective in strengthening vitamin K-dependent carboxylation, and could improve vitamin A status.

Immune cell-specific smoking-related expression characteristics are revealed by re-analysis of transcriptomes from the CEDAR cohort.

Introduction: Smoking is known to affect whole-blood expression and methylation profiles. Although whole-genome methylation studies indicated that effects observed in blood may be driven by changes within leukocyte subtypes, these phenomena have not been explored using expression profiling. Material and methods: This study reanalyzed data from the Correlated Expression and Disease Association Research (CEDAR) patient cohort recruited by Momozawa et al. (E-MTAB-6667). Data from gene expression profiling of immunomagnetically sorted CD4+, CD8+, CD14+, CD15+, and CD19+ cells were processed. Differential expression analyses were conducted in each immune cell type, followed by gene ontology analysis and supplementary investigations. Results: Ninety-four differentially expressed genes were found (CD8+ n = 58, CD14+ n = 20, CD4+ n = 14, CD19+ n = 2). Two key smoking-related genes were overexpressed in specific cell types: LRRN3 (CD4+, CD8+) and MMP25 (CD8+, CD14+). In CD4+ cells smoking was associated with reduced expression of the NK cell receptor KLRB1, suggesting CD4+ subpopulation shifts and differences in interferon signaling (reduced IRF1 and IL18RAP in smokers). Key results and their integration with an immune protein-protein interaction network revealed that smoking influences integrins in CD8+ cells (ITGB7, ITGAL, ITGAM, ITGB2). C-type lectin CLEC4A was reduced in CD8+ cells and CLEC10A was increased in CD14+ cells from smokers; moreover, CLEC5A (CD8+), CLEC7A (CD8+) and CLEC9A (CD19+) were related to smoking in supplementary analyses. CD14+ cells from smokers exhibited overexpression of LDLR and the formyl peptide receptor FPR3. Conclusions: Smoking specifically alters vital immune regulation genes in lymphocyte subtypes, especially CD4+, CD8+ and CD14+ cells.

Preclinical atherosclerosis in cystic fibrosis: Two distinct presentations are related to pancreatic status.

BACKGROUND: Patients with cystic fibrosis (CF) are exposed to overlapping cardiovascular risk factors. We hypothesized that CF is characterized by increased arterial stiffness and greater intima-media thickness (IMT). METHODS: This cross-sectional study assessed the digital volume pulse arterial stiffness index (SIDVP) using photopletysmography, measured intima-media complex thickness (IMT) at the common carotid artery, and obtained an extended set of clinical and atherosclerosis-related laboratory parameters. RESULTS: Fifty-five patients with moderate-to-severe CF (mean age 26.3±8.6 years, BMI 20.3±3.1 kg/m2, FEV1 62±26%) and 51 healthy controls (25.1±4.4 years, BMI 21.7±3.0 kg/m2) entered the study. SIDVP was greater in pancreatic insufficient (PI), but not pancreatic sufficient (PS) CF patients compared with control (7.3±1.8 m/s vs 6.0±1.2 m/s; p=7.1 × 10-5). IMT was increased in PS (but not PI) participants relative to control (552±69 µm vs 456±95 µm, p=0.0011). SIDVP was also greater in PI than in PS patients (7.3±1.8 m/s vs 6.3±1.7 m/s, p=0.0232) and IMT was higher in PS compared with PI (552±69 µm vs 453±82 µm, p=0.0002). SIDVP independently associated with age, PI, the lack of liver cirrhosis, and with Pseudomonas aeruginosa colonization. PS was the only independent correlate of IMT in CF. CONCLUSIONS: PI patients are at risk of developing general arterial stiffness. PS may relate to carotid IMT thickening, which underscores the need for further study that could lead to reconsideration of dietary guidance in PS CF.

HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn's disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

The Impact of ERASMUS Exchanges on the Professional and Personal Development of Medical Students.

The ERASMUS program is one of the most popular student exchange projects, particularly among the students of Central and Eastern European countries. However, limited research is available with regard to its influence on the professional and personal development of its participants. The study aimed at investigating the experiences and impact of the ERASMUS program on different domains of the personal and professional life of medical students. A questionnaire containing closed and open-ended questions was distributed among 269 former participants of the ERASMUS program from the Poznan University of Medical Sciences to collect qualitative and quantitative data regarding the topic. The response rate was 41%. Mastering professional foreign language skills was the most frequently reported benefit of ERASMUS (94%), followed by a change of approach towards learning by exposure to innovative teaching techniques, character, professionalism and cultural competency development, impact on the migration decisions of the students, as well as the opportunity to compare healthcare and educational systems across countries. Additionally, 57% of respondents stated that ERASMUS impacted their career plans, and few indicated that it had affected their specialty choice. Approximately 28% of respondents have worked abroad in healthcare or research since graduating. Participation in the ERASMUS program proved to be a unique opportunity for professional and personal development.

Analysis of Gastrointestinal Acoustic Activity Using Deep Neural Networks.

Automated bowel sound (BS) analysis methods were already well developed by the early 2000s. Accuracy of ~90% had been achieved by several teams using various analytical approaches. Clinical research on BS had revealed their high potential in the non-invasive investigation of irritable bowel syndrome to study gastrointestinal motility and in a surgical setting. This article proposes a novel methodology for the analysis of BS using hybrid convolutional and recursive neural networks. It is one of the first methods of using deep learning to be widely explored. We have developed an experimental pipeline and evaluated our results with a new dataset collected using a device with a dedicated contact microphone. Data have been collected at night-time, which is the most interesting period from a neurogastroenterological point of view. Previous works had ignored this period and instead kept brief records only during the day. Our algorithm can detect bowel sounds with an accuracy >93%. Moreover, we have achieved a very high specificity (>97%), crucial in diagnosis. The results have been checked with a medical professional, and they successfully support clinical diagnosis. We have developed a client-server system allowing medical practitioners to upload the recordings from their patients and have them analyzed online. This system is available online. Although BS research is technologically mature, it still lacks a uniform methodology, an international forum for discussion, and an open platform for data exchange, and therefore it is not commonly used. Our server could provide a starting point for establishing a common framework in BS research.

Automated Bowel Sound Analysis: An Overview.

Despite technological progress, we lack a consensus on the method of conducting automated bowel sound (BS) analysis and, consequently, BS tools have not become available to doctors. We aimed to briefly review the literature on BS recording and analysis, with an emphasis on the broad range of analytical approaches. Scientific journals and conference materials were researched with a specific set of terms (Scopus, MEDLINE, IEEE) to find reports on BS. The research articles identified were analyzed in the context of main research directions at a number of centers globally. Automated BS analysis methods were already well developed by the early 2000s. Accuracy of 90% and higher had been achieved with various analytical approaches, including wavelet transformations, multi-layer perceptrons, independent component analysis and autoregressive-moving-average models. Clinical research on BS has exposed their important potential in the non-invasive diagnosis of irritable bowel syndrome, in surgery, and for the investigation of gastrointestinal motility. The most recent advances are linked to the application of artificial intelligence and the development of dedicated BS devices. BS research is technologically mature, but lacks uniform methodology, an international forum for discussion and an open platform for data exchange. A common ground is needed as a starting point. The next key development will be the release of freely available benchmark datasets with labels confirmed by human experts.

Ileal Lactase Expression Associates with Lactase Persistence Genotypes.

(1) Background: Lactose digestion depends on persistence genotypes (including rs4988235), the frequency of which exhibits broad geographical variability. However, little is known about the relationship between lactase (LCT) genotypes and intestinal expression of LCT. We aimed to investigate ileal expression of LCT depending on main genetic polymorphisms (rs4988235, rs3754689, rs3739022), age, sex, smoking status, body mass index (BMI), and the expression of other genes; (2) Methods: phenotype, array-based genotype, and ileal mucosal biopsy expression data were obtained from the CEDAR study; (3) Results: analyses included 196 healthy Europeans (53.6% women) aged 53.0 ± 13.6 years with a mean BMI of 25.6 ± 4.2 kg/m2, of whom 17.4% were smoking. Ileal LCT expression was mostly independent of age, sex, BMI, or smoking. Rs4988235 homozygous minor allele (GG) associated with lower LCT expression (vs. AG p = 2.2 × 10-6, vs. AA p = 1.1 × 10-7). Homozygous major allele of rs3754689 (GG) was related to higher LCT expression (vs. AG p = 1.7 × 10-5, vs. AA p = 0.0074). Rs3754689 genotype did not modify LCT expression (GG vs. AG p = 0.051) in rs4988235-heterozygous subgroup. Interestingly, CD14, which is a marker of monocytes and macrophages, was the strongest negative transcriptomic correlate of LCT expression (r = -0.57, pFDR = 1.1 × 10-14); (4) Conclusions: both rs4988235 and rs3754689 associated with ileal LCT expression, which did not seem related to age, sex, smoking, or BMI. The inverse correlation between LCT and CD14 expression in the ileum is striking and requires further investigation.

Leukocyte Telomere Length Is Not Reduced in Children and Adults with Cystic Fibrosis but Associates with Clinical Characteristics-A Cross-Sectional Study.

We hypothezied that telomere length is considerably altered in cystic fibrosis (CF) patients compared to healthy subjects (HS), and that leukocyte telomere length variation reflects the severity of CF. Relative telomere length (RTL) was assessed by qPCR in 70 children aged 5-10 (34 CF; 36 HS) and 114 adults aged 18-45 (53 CF; 61 HS). Telomere length was similar in CF and HS (median (interquartile range): 0.799 (0.686-0.950) vs. 0.831 (0.707-0.986); p = 0.5283) both in children and adults. In adults, women had longer telomeres than men (0.805 (0.715-0.931) vs. 0.703 (0.574-0.790); p = 0.0002). Patients treated with inhaled corticosteroids had a shorter RTL compared to those without steroid therapy (0.765 (0.664-0.910) vs. 0.943 (0.813-1.191); p = 0.0007) and this finding remained significant after adjusting for gender, age, BMI, and child/adult status (p = 0.0003). Shorter telomeres were independently associated with the presence of comorbidities (0.763 (0.643-0.905) vs. 0.950 (0.783-1.130); p = 0.0006) and antibiotic treatment at the moment of blood sampling (0.762 (0.648-0.908) vs. 0.832 (0.748-1.129); p = 0.0172). RTL correlated with number of multiple-day hospitalizations (rho = -0.251; p = 0.0239), as well as number of hospitalization days (rho = -0.279; p = 0.0113). Leukocyte RTL in children and adults with CF was not shorter than in healthy controls, and did not seem to have any potential as a predictor of CF survival. However, it inversely associated with the investigated clinical characteristics.

The Effect of Sodium Butyrate Enemas Compared with Placebo on Disease Activity, Endoscopic Scores, and Histological and Inflammatory Parameters in Inflammatory Bowel Diseases: A Systematic Review of Randomised Controlled Trials.

INTRODUCTION: Administration of butyrate enemas might improve the health status of patients with inflammatory bowel disease (IBD). However, the results seem equivocal. Therefore, this systematic review aimed to assess the effect of sodium butyrate enemas on disease activity index (DAI), endoscopic scores, as well as histological and inflammatory parameters in IBD patients. METHODS: The PubMed, Scopus, Web of Science, and Cochrane databases were searched. Randomised controlled trials published in English that assessed the effect of butyrate enemas on DAI, clinical symptoms, inflammatory markers, as well as histological and endoscopic scores in patients with Crohn's disease (CD) and ulcerative colitis (UC) were included in the analysis. RESULTS: Eight studies involving 227 UC patients were included in this analysis. Only one study reported significant differences in DAI between groups. Besides, butyrate treatment groups did not differ significantly from controls concerning the effect on endoscopic and histological scores. Moreover, butyrate enemas exerted a significant effect on few inflammatory parameters measured in colonic mucosal biopsies. CONCLUSION: The current evidence is limited and does not support the application of butyrate enemas in UC. There are no reliable data regarding the efficacy of butyrate enemas in CD. The systematic review protocol was registered in the PROSPERO database (CRD42020163654).

Whose Tweets on COVID-19 Gain the Most Attention: Celebrities, Political, or Scientific Authorities?

Twitter has considerable capacity for health education and proves to be an efficient and accessible communication tool in the coronavirus disease-19 (COVID-19) pandemic. Although many stakeholders saturate Twitter with COVID-19-related information, it remains unknown who disseminates information most efficaciously. COVID-19-related tweets were obtained from Twitter accounts of health agencies, governmental authorities, universities, scientific journals, medical associations, and celebrities. Posts' impact was measured with the nominal and relative (%followers) number of likes and retweets. A sentiment analysis was conducted.We have identified 17,331 COVID-19-related tweets posted by 338 accounts in >4 months since the virus began to spread. The largest number of likes was received by tweets of celebrities (median nominal, relative likes; 14,918, 0.036 percent), politicians (259, 0.174 percent), and health agencies (231, 0.007 percent). Most retweeted messages were also posted by celebrities (2,366, 0.005 percent), health agencies (130, 0.004 percent), and politicians (55, 0.041 percent). Retweets and likes peaked in March 2020, and the overall sentiment of the tweets was growing steadily. Whereas celebrities and politicians posted positive messages, the scientific and health authorities often employed a negative vocabulary. The posts with positive sentiment gained more likes and relative likes than nonpositive. During the pandemic, the tweets of celebrities and politicians related to COVID-19 outperform those coming from health and scientific institutions. Active engagement of Twitter influencers may help key messages go viral.

Infant formula fatty acid profile following microwave heating.

Microwave heating of foods may alter their content. Yet, parents commonly heat infant formula in the microwave oven. The study aimed at understanding whether microwave heating of formula changes its fatty acid (FA) composition. Portions of infant formula were prepared and divided in three parts: control (sampled twice: at the start and after 30 minutes), microwave (sampled twice: after reaching 37°C and 50°C), and water bath (sampled twice: after reaching 37°C and 50°C). In thus obtained samples, a total profile of 25 FA was assessed using gas chromatography-mass spectrometry. Overall, fourteen portions were prepared, which were sampled 84 times yielding 2075 individual total FA level measurements. Few differences were identified between the microwave, control, and water bath groups. Microwave warming to 37°C was associated with increases of C12 (median increased by +0.40%, p = 0.0063), C14 (+0.05%, p = 0.0091), and C4 content (+6.90%, p = 0.0131). Microwaving up to 50°C slightly decreased C16:1trans (-5.00%, p = 0.0463) and C18:2trans1 (-5.13%, p = 0.0231). A paired comparison of pooled control and microwaved samples revealed increases in C12 (+0.18%, p = 0.0490) as well as a loss of C18:2trans1 (also -5.13%, p = 0.0073) and C18:2trans3 (-5.56%, p = 0.0042) after microwave treatment. C18:2trans1 (-2.63%, p = 0.0132) and C18:3trans1 (-2.26%, p = 0.0434) were lower in microwaved samples compared with the water bath. A slightly lower C18:2 content was found in the water bath samples than in the control groups (-0.11%, p = 0.0430). None of these differences would remain significant after a correction for multiple comparisons. Microwave heating of infant formula to 37°C or 50°C might marginally alter its total FA profile. Further studies are required to determine whether it alters the rate of free radical formation.

Global and local diet popularity rankings, their secular trends, and seasonal variation in Google Trends data.

OBJECTIVES: The Internet has become the main source of health-related information including nutrition. The aim of this study was to rank the most popular diets among Google users globally and regionally in addition to secular and seasonal trends in the years 2004 to 2019. METHODS: We used Google Trends (GT) to identify and analyze course over time and regional interest of 47 topics related to diets. We analyzed secular trends using the Seasonal Mann-Kendall test and seasonal variation using time-series decomposition. The topic "Mediterranean diet" (MedD) was used as a benchmark. We calculated the interest of all topics in proportion to the relative search volume (RSV) of MedD. RESULTS: Globally, Google users were particularly interested in veganism (19.54 times higher than MedD), vegetarianism (15.09 times higher than MedD), and gluten-free diet (11.11 times higher than MedD). Veganism was the most frequently searched diet type in 23 countries followed by vegetarianism (14), ketogenic diet (7), and low-carbohydrate diet (7). Whereas an increase of RSV over time was observed for 23 diets, a decrease was noted for 20. The most dynamic increase was found for FODMAP (6.12 RSV/year), gluten-free diet (5.95 RSV/year), and raw veganism (5.72 RSV/year). Sharp declines concerned negative-calorie food (-4.34 RSV/year), macrobiotic diet (-3.89 RSV/year), and cabbage soup diet (-3.50 RSV/year). The interest in most diets falls in December but peaks in January. CONCLUSION: Veganism, vegetarianism, and gluten-free diet attract the largest public interest globally. Both secular trends and seasonal variation shape the ever-changing landscape of diet popularity. GT holds promise as a valuable tool in local and international nutrition research.