Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.

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.

Modeling the COVID-19 epidemic in Croatia: a comparison of three analytic approaches.

AIM: To facilitate the development of a COVID-19 predictive model in Croatia by analyzing three different methodological approaches. METHOD: We used the historical data to explore the fit of the extended SEIRD compartmental model, the Heidler function, an exponential approximation in analyzing electromagnetic phenomena related to lightning strikes, and the Holt-Winters smoothing (HWS) for short-term epidemic predictions. We also compared various methods for the estimation of R0. RESULTS: The R0 estimates for Croatia varied from 2.09 (95% CI 1.77-2.40) obtained by using an empirical post-hoc method to 2.28 (95% CI 2.27-2.28) when we assumed an exponential outbreak at the very beginning of the COVID-19 epidemic in Croatia. Although the SEIRD model provided a good fit for the early epidemic stages, it was outperformed by the Heidler function fit. HWS achieved accurate short-term predictions and depended the least on model entry parameters. Neither model performed well across the entire observed period, which was characterized by multiple wave-form events, influenced by the re-opening for the tourist season during the summer, mandatory masks use in closed spaces, and numerous measures introduced in retail stores and public places. However, an extension of the Heidler function achieved the best overall fit. CONCLUSIONS: Predicting future epidemic events remains difficult because modeling relies on the accuracy of the information on population structure and micro-environmental exposures, constant changes of the input parameters, varying societal adherence to anti-epidemic measures, and changes in the biological interactions of the virus and hosts.

The Role of Socioeconomic Status in Adherence to the Mediterranean Diet and Body Mass Index Change: A Follow-Up Study in the General Population of Southern Croatia.

The Mediterranean diet (MD) is one of the most healthful dietary patterns, beneficial for humans and the environment. However, the MD has recently exhibited a declining trend, especially in younger and less affluent people. This study investigated the association between socioeconomic indicators and adherence to the MD in 4671 adult subjects from Dalmatia, Croatia (age range 18-98 years; 61.9% were women). Additionally, in the follow-up we examined the change in adherence to the MD and in BMI (subsample, N = 1342; 62.5% were women; mean follow-up time of 5.8 years). The adherence to the MD was based on the Mediterranean Diet Serving Score (range 0-24 points, cut-off value ≥ 14 points), with a prevalence in the overall sample of 28.5%. Higher odds of adherence to the MD were recorded in women, older subjects, and those with higher level of objective material status, while it was less likely in the period after economic crisis of 2007-2008. Additionally, we detected no change in adherence to the MD in the follow-up subsample (-8.5%, p = 0.056), but there was an increase in BMI (+6.5%, p < 0.001). We recorded an increase in adherence for nuts (+127.5%), sweets (+112.6%), red meat (+56.4%), and wine (+50.0%), unlike the reduction in adherence for vegetables (-35.1%), fish (-23.4%), white meat (-11.6%), cereals (-10.9%), and dairy products (-9.6%). Similar results were obtained across all quartiles of objective material status. Over time, the absolute change in the MD score was positively associated with female gender, age, higher education, and moderate physical activity, but it was negatively associated with adherence to the MD at baseline. BMI change was positively associated with female gender, and negatively with initial BMI, initial adherence to the MD, and MD change. Our findings point towards a less than ideal adherence to the MD in the general population of southern Croatia, and identify important characteristics associated with adherence change over time, informing necessary interventions aimed at increasing MD uptake.

Does Each Menstrual Cycle Elicit a Distinct Effect on Olfactory and Gustatory Perception?

The obesity pandemic has brought forth a scientific interest in food intake and sensory perception interactions. Olfactory perception and gustatory perception are very complex and under the influence of many factors, including the menstrual cycle. This study aims to clarify conflicting findings on the influence of the menstrual cycle on olfactory and gustatory perception. Women were assessed during four consecutive phases of one complete cycle (mid-follicular, ovulatory, mid-luteal, and late luteal phases (N = 21)), in contrast to women measured across the same phases belonging to two menstrual cycles (N = 29). Additional control groups were men (N = 17), postmenopausal women (N = 14), oral contraceptive users (N = 10), and women with an anovulatory cycle (N = 8). Olfactory threshold, odor discrimination, and identification were tested using the "Sniffin Sticks" test kit. Suprathreshold intensity and hedonic ratings for sweet, salty, sour, and bitter solutions were assessed. One-way ANOVA and ANOVA for repeated measurements was applied in the analysis, along with linear and trigonometric data fitting and linear mixed models. Linear increases in olfactory discrimination, identification, and overall olfactory performance were observed only in women followed across a complete menstrual cycle. Compared to other groups, these women displayed a cyclic pattern characterized by a predilection for sweet solution; reduced distaste for salty and sour solutions; and increased intensity perception of salty, sour, and bitter solutions towards the end of the cycle. These results suggest that a distinct hormonal milieu of a complete menstrual cycle may be affecting both olfactory and gustatory perception.

Searching for carbonylome biomarkers of aging - development and validation of the proteomic method for quantification of carbonylated protein in human plasma.

AIM: To develop a method for measuring protein carbonylation in human plasma and serum samples, which was previously implied in numerous age-related phenotypes. METHODS: Protein expression and carbonylation were analyzed in plasma samples obtained from 12 healthy human individuals by using a novel method that combines affinity-based albumin and immunoglobulin G removal, and aminooxy dyeing in one- or two-dimensional gels. In addition, carbonylome profile of plasma and serum was compared. Coefficients of variation and intra-class correlation coefficients were used in statistical analysis. RESULTS: Following a step-wise laboratory development and optimization process, we measured the protein expression and carbonylation for 813 proteins from the plasma. The analysis of repeated measurements suggested excellent coefficients of variation, which rarely exceeded 10%. The average value of intra-class correlation based on absolute agreement (ICC) for protein expression was 0.97±0.02, while for carbonylation it was 0.73±0.24. The removal of the most extreme protein outlier in carbonylation assessment increased the average ICC to 0.87±0.04. Low protein spot volume substantially reduced repeatability. Serum carbonylation estimates were similar to those from plasma, with the ICC in the range of 0.86-0.89. CONCLUSION: We developed a reliable method for the measurement of human plasma protein carbonylation, which can be used for the assessment of carbonylome biomarkers of aging.

Awakening cortisol indicators, advanced glycation end products, stress perception, depression and anxiety in parents of children with chronic conditions.

This cross-sectional study aims to investigate awakening cortisol indicators and to explore their association with stress perception, advanced glycation end products (AGEs), depression and anxiety in parents of children with chronic conditions. We included five parental groups according to children's diagnoses: Down syndrome (DS; N = 31), autistic spectrum disorder (ASD; N = 29), cerebral palsy (CP; N = 15), diabetes mellitus type 1 (DMT1; N = 38), and a control group of heathy children (CG; N = 33). Salivary cortisol and AGEs were measured, alongside with psychological indices. Partial correlation and multiple linear regression were used in the analysis to identify parental characteristics associated with total awakening cortisol output (area under the curve with respect to the ground, AUCG), cortisol awakening response (area under the curve with respect to the increase, AUCI), perceived stress, and health outcomes (AGEs, depression and anxiety). There was no difference between groups for AUCG, while DS and DMT1 groups showed reduced AUCI (ß = -0.241, p = 0.040; ß = -0.249, p = 0.028, respectively), and ASD parents had a borderline insignificant result (ß = -0.205, p = 0.081). Non-smokers had higher AUCG, and parental sedentary activity and sleep duration were associated with AUCI. AUCG was positively associated with AGEs (ß = 0.218, p = 0.013), anxiety (ß = 0.207, p = 0.004), and with depression (ß = 0.156, p = 0.034), unlike the AUCI. DS parental group showed lower general stress perception (ß = -0.260, p = 0.005). Parents of children with DMT1 had more pronounced depressive symptoms (ß = 0.183, p = 0.039), while CP parents had a borderline insignificant result for depression (ß = 0.143, p = 0.058). Based on these results, parents of children with chronic conditions have altered awaking cortisol response and are under increased risk of adverse health consequences.

The Association between Salt Taste Perception, Mediterranean Diet and Metabolic Syndrome: A Cross-Sectional Study.

Metabolic syndrome (MetS) is a widespread disorder and an important public health challenge. The purpose of this study was to identify the association between salt taste perception, Mediterranean diet and MetS. This cross-sectional study included 2798 subjects from the general population of Dalmatia, Croatia. MetS was determined using the Joint Interim Statement definition, and Mediterranean diet compliance was estimated using Mediterranean Diet Serving Score. Salt taste perception was assessed by threshold and suprathreshold testing (intensity and hedonic perception). Logistic regression was used in the analysis, adjusting for important confounding factors. As many as 44% of subjects had MetS, with elevated waist circumference as the most common component (77%). Higher salt taste sensitivity (lower threshold) was associated with several positive outcomes: lower odds of MetS (OR = 0.69; 95% CI 0.52-0.92), lower odds for elevated waist circumference (0.47; 0.27-0.82), elevated fasting glucose or diabetes (0.65; 0.45-0.94), and reduced HDL cholesterol (0.59; 0.42-0.84), compared to the higher threshold group. Subjects with lower salt taste threshold were more likely to consume more fruit, and less likely to adhere to olive oil and white meat guidelines, but without a difference in the overall Mediterranean diet compliance. Salt taste intensity perception was not associated with any of the investigated outcomes, while salty solution liking was associated with MetS (OR = 1.85, CI 95% 1.02-3.35). This study identified an association between salt taste perception and MetS and gave a new insight into taste perception, nutrition, and possible health outcomes.

Have Lifestyle Habits and Psychological Well-Being Changed among Adolescents and Medical Students Due to COVID-19 Lockdown in Croatia?

OBJECTIVE: To investigate dietary habits, sleep and psychological well-being of adolescents and medical students during COVID-19 lockdown in Split, Croatia. METHODS: 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. RESULTS: 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 p < 0.001), and perceived stress in students (p = 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 p < 0.001). Interestingly, higher MD adherence was correlated with less perceived hardship and greater happiness and QoL during lockdown. CONCLUSION: 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.