To investigate dietary habits, sleep and psychological well-being of adolescents and medical students during COVID-19 lockdown in Split, Croatia.
We surveyed 1326 students during 2018 and 2019, and ...compared their responses with 531 students enrolled in May 2020. Perceived stress, quality of life (QoL), happiness, anxiety, and optimism were assessed as proxies of psychological well-being, using general linear modelling.
We found no substantial differences in dietary pattern between pre-lockdown and lockdown periods, including the overall Mediterranean diet (MD) adherence. However, the MD pattern changed, showing increased adherence to the MD pyramid for fruit, legumes, fish, and sweets, while cereals, nuts, and dairy intake decreased during COVID-19 lockdown. A third of students reported weight loss during lockdown, 19% reported weight gain, while physical activity remained rather stable. The most prominent change was feeling refreshed after a night's sleep, reported by 31.5% of students during lockdown vs. 8.5% before; median length of sleep duration increased by 1.5 h. Lockdown significantly affected QoL, happiness, optimism (all
< 0.001), and perceived stress in students (
= 0.005). MD adherence was positively correlated with QoL and study time, and negatively with TV and mobile phone use in pre-lockdown period (all
< 0.001). Interestingly, higher MD adherence was correlated with less perceived hardship and greater happiness and QoL during lockdown.
These insights provide valuable information for tailored interventions aimed at maintaining healthy lifestyle in young population. Given the numerous beneficial effects associated with MD adherence, modification of lifestyle through application of lifestyle medicine deserves a priority approach.
Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation ...or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins - glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.
Mediterranean diet (MD) is among the most commonly investigated diets and recognized as one of the healthiest dietary patterns. Due to its complexity, geographical and cultural variations, it also ...represents a challenge for quantification. The aim of this cross-sectional study was to assess reliability and validity of the Croatian version of the 14-item Mediterranean Diet Serving Score (MDSS), using the Mediterranean Diet Adherence Screener (MEDAS) as the referent test. We included the exploratory sample of 360 medical students, and a confirmatory sample of 299 health studies students from the University of Split, Croatia. Test-retest reliability and validity of the MDSS were tested using intra-class correlation coefficients (ICC), while Cohen's kappa statistic was used to test correct classification of subjects into MD adherent/non-adherent category. A very good reliability was shown for the overall MDSS score (ICC = 0.881 95% CI 0.843-0.909), and a moderate reliability for the binary adherence (κ = 0.584). Concurrent validity of the MDSS was also better when expressed as a total score (ICC = 0.544 0.439-0.629) as opposed to the adherence (κ = 0.223), with similar result in the confirmatory sample (ICC = 0.510 0.384-0.610; κ = 0.216). Disappointingly, only 13.6% of medical students were adherent to the MD according to MDSS, and 19.7% according to the MEDAS questionnaire. Nevertheless, MDSS score was positively correlated with age (ρ = 0.179: P = 0.003), self-assessed health perception (ρ = 0.123; P = 0.047), and mental well-being (ρ = 0.139: P = 0.022). MDSS questionnaire is a short, reliable and reasonably valid instrument, and thus useful for assessing the MD adherence, with better results when used as a numeric score, even in the population with low MD adherence.
All immunoglobulin G molecules carry N-glycans, which modulate their biological activity. Changes in N-glycosylation of IgG associate with various diseases and affect the activity of therapeutic ...antibodies and intravenous immunoglobulins. We have developed a novel 96-well protein G monolithic plate and used it to rapidly isolate IgG from plasma of 2298 individuals from three isolated human populations. N-glycans were released by PNGase F, labeled with 2-aminobenzamide and analyzed by hydrophilic interaction chromatography with fluorescence detection. The majority of the structural features of the IgG glycome were consistent with previous studies, but sialylation was somewhat higher than reported previously. Sialylation was particularly prominent in core fucosylated glycans containing two galactose residues and bisecting GlcNAc where median sialylation level was nearly 80%. Very high variability between individuals was observed, approximately three times higher than in the total plasma glycome. For example, neutral IgG glycans without core fucose varied between 1.3 and 19%, a difference that significantly affects the effector functions of natural antibodies, predisposing or protecting individuals from particular diseases. Heritability of IgG glycans was generally between 30 and 50%. The individual's age was associated with a significant decrease in galactose and increase of bisecting GlcNAc, whereas other functional elements of IgG glycosylation did not change much with age. Gender was not an important predictor for any IgG glycan. An important observation is that competition between glycosyltransferases, which occurs in vitro, did not appear to be relevant in vivo, indicating that the final glycan structures are not a simple result of competing enzymatic activities, but a carefully regulated outcome designed to meet the prevailing physiological needs.
Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies ...allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects.Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes.
Many existing cohorts contain a range of relatedness between genotyped individuals, either by design or by chance. Haplotype estimation in such cohorts is a central step in many downstream analyses. ...Using genotypes from six cohorts from isolated populations and two cohorts from non-isolated populations, we have investigated the performance of different phasing methods designed for nominally 'unrelated' individuals. We find that SHAPEIT2 produces much lower switch error rates in all cohorts compared to other methods, including those designed specifically for isolated populations. In particular, when large amounts of IBD sharing is present, SHAPEIT2 infers close to perfect haplotypes. Based on these results we have developed a general strategy for phasing cohorts with any level of implicit or explicit relatedness between individuals. First SHAPEIT2 is run ignoring all explicit family information. We then apply a novel HMM method (duoHMM) to combine the SHAPEIT2 haplotypes with any family information to infer the inheritance pattern of each meiosis at all sites across each chromosome. This allows the correction of switch errors, detection of recombination events and genotyping errors. We show that the method detects numbers of recombination events that align very well with expectations based on genetic maps, and that it infers far fewer spurious recombination events than Merlin. The method can also detect genotyping errors and infer recombination events in otherwise uninformative families, such as trios and duos. The detected recombination events can be used in association scans for recombination phenotypes. The method provides a simple and unified approach to haplotype estimation, that will be of interest to researchers in the fields of human, animal and plant genetics.
Infectious diseases still threaten global human health, and host genetic factors have been indicated as determining risk factors for observed variations in disease susceptibility, severity, and ...outcome. We performed a genome-wide meta-analysis on 4624 subjects from the 10,001 Dalmatians cohort, with 14 infection-related traits. Despite a rather small number of cases in some instances, we detected 29 infection-related genetic associations, mostly belonging to rare variants. Notably, the list included the genes CD28, INPP5D, ITPKB, MACROD2, and RSF1, all of which have known roles in the immune response. Expanding our knowledge on rare variants could contribute to the development of genetic panels that could assist in predicting an individual's life-long susceptibility to major infectious diseases. In addition, longitudinal biobanks are an interesting source of information for identifying the host genetic variants involved in infectious disease susceptibility and severity. Since infectious diseases continue to act as a selective pressure on our genomes, there is a constant need for a large consortium of biobanks with access to genetic and environmental data to further elucidate the complex mechanisms behind host-pathogen interactions and infectious disease susceptibility.
Purpose To develop a classification and grading system for myopic maculopathy. Design Development and evaluation of a classification system for myopic maculopathy based on observational case series. ...Methods A comprehensive set of myopic macular lesions was defined via literature review and through consensus meetings among retinal specialists and clinician scientists. A classification of myopic maculopathy was formulated based on fundus photographs and a modified Delphi process and consensus. Inter- and intraobserver reproducibility, assessed as agreement (%) and weighted kappa values, were evaluated. One hundred retinal photographs with myopia and myopic macular lesions were selected from case series at the High Myopia Clinic of the Tokyo Medical and Dental University, Tokyo, Japan. Results We defined 5 categories of myopic maculopathy including “no myopic retinal degenerative lesion” (Category 0), “tessellated fundus” (Category 1), “diffuse chorioretinal atrophy” (Category 2), “patchy chorioretinal atrophy” (Category 3), and “macular atrophy” (Category 4). Three additional features to supplement these categories were defined as “plus” lesions, namely, lacquer cracks, myopic choroidal neovascularization, and Fuchs spot. Posterior staphyloma was considered as a further, important sign of myopic retinopathy. The intraobserver agreement was ≥85% and the corresponding weighted kappa statistic was ≥0.6 between observations. After a brief training session, interobserver kappa statistics reached the predefined satisfactory level (≥0.4), considered as above moderate agreement. Conclusions We propose a classification system for myopic maculopathy that was found to be reproducible. Applying a uniform classification in different studies will facilitate communication and comparison of findings from clinical trials and epidemiologic studies.
Fine structural details of glycans attached to the conserved N-glycosylation site significantly not only affect function of individual immunoglobulin G (IgG) molecules but also mediate inflammation ...at the systemic level. By analyzing IgG glycosylation in 5,117 individuals from four European populations, we have revealed very complex patterns of changes in IgG glycosylation with age. Several IgG glycans (including FA2B, FA2G2, and FA2BG2) changed considerably with age and the combination of these three glycans can explain up to 58% of variance in chronological age, significantly more than other markers of biological age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age. Thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. Considering the important role of IgG glycans in inflammation, and because the observed changes with age promote inflammation, changes in IgG glycosylation also seem to represent a factor contributing to aging.
Glycosylation is the key posttranslational mechanism that regulates function of immunoglobulins, with multiple systemic repercussions to the immune system. Our study of IgG glycosylation in 5,117 individuals from four European populations has revealed very extensive and complex changes in IgG glycosylation with age. The combined index composed of only three glycans explained up to 58% of variance in age, considerably more than other biomarkers of age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age; thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. The ability to measure human biological aging using molecular profiling has practical applications for diverse fields such as disease prevention and treatment, or forensics.
The biological and clinical relevance of glycosylation is becoming increasingly recognized, leading to a growing interest in large-scale clinical and population-based studies. In the past few years, ...several methods for high-throughput analysis of glycans have been developed, but thorough validation and standardization of these methods is required before significant resources are invested in large-scale studies. In this study, we compared liquid chromatography, capillary gel electrophoresis, and two MS methods for quantitative profiling of N-glycosylation of IgG in the same data set of 1201 individuals. To evaluate the accuracy of the four methods we then performed analysis of association with genetic polymorphisms and age. Chromatographic methods with either fluorescent or MS-detection yielded slightly stronger associations than MS-only and multiplexed capillary gel electrophoresis, but at the expense of lower levels of throughput. Advantages and disadvantages of each method were identified, which should inform the selection of the most appropriate method in future studies.
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