Strong association of TLR2 and TLR3 polymorphisms with keratoacanthoma and common warts: a case-control study.

AIM: To determine variations in allele and genotype frequencies between keratoacanthoma (KA) and common warts (CW), compared with the control group, in three single nucleotide polymorphisms (SNPs) within the TLR2, TLR3, and TLR9 genes. METHODS: This case-control study involved samples from 161 patients with KA, 152 patients with CW, and 469 controls. DNA was isolated from formalin-fixed paraffin-embedded tissue sections. Three SNPs - rs4696480 in TLR2, rs7657186 in TLR9, and rs35213 in TLR3 - were genotyped with TaqMan Genotyping Assays on the 7500 Real-Time PCR System. RESULTS: TLR2 rs4696480 and TLR3 rs7657186 were significantly overrepresented in KA and CW compared with controls (P<0.001). The association was stronger for CW than for KA, as evidenced by higher frequencies of the A allele and AA genotype for rs4696480. Both KA and CW patients had higher frequencies of the G allele and GG genotype for rs7657186 than controls. rs7657186 was moderately associated with KA and CW, with the G allele and GG genotype being more prevalent in CW cases, where no AA homozygotes were found. CONCLUSION: Genetic variants in TLR2 (rs4696480) and TLR3 (rs7657186) genes may affect KA and CW development, influencing immune responses and susceptibility to these skin lesions. Further research is required to elucidate TLR expression patterns and their role in KA development.

Differences in Plasma Cannabidiol Concentrations in Women and Men: A Randomized, Placebo-Controlled, Crossover Study.

The potential therapeutic benefits of cannabidiol (CBD) require further study. Here, we report a triple-blind (participant, investigator, and outcome assessor) placebo-controlled crossover study in which 62 hypertensive volunteers were randomly assigned to receive the recently developed DehydraTECH2.0 CBD formulation or a placebo. This is the first study to have been conducted using the DehydraTECH2.0 CBD formulation over a 12-week study duration. The new formulation's long-term effects on CBD concentrations in plasma and urine, as well as its metabolites 7-hydroxy-CBD and 7-carboxy-CBD, were analyzed. The results of the plasma concentration ratio for CBD/7-OH-CBD in the third timepoint (after 5 weeks of use) were significantly higher than in the second timepoint (after 2.5 weeks of use; p = 0.043). In the same timepoints in the urine, a significantly higher concentration of 7-COOH-CBD was observed p < 0.001. Differences in CBD concentration were found between men and women. Plasma levels of CBD were still detectable 50 days after the last consumption of the CBD preparations. Significantly higher plasma CBD concentrations occurred in females compared to males, which was potentially related to greater adipose tissue. More research is needed to optimize CBD doses to consider the differential therapeutic benefits in men and women.

Clinical characteristics and laboratory parameters of deep venous thrombosis after SARS-CoV-2 infection in a non-hospital setting - a single-center retrospective study.

AIM: To assess the differences in clinical and laboratory parameters of non-hospitalized patients with deep venous thrombosis (DVT) according to the SARS-CoV-2 status. METHODS: We retrospectively reviewed demographic, clinical, laboratory, and ultrasound data of adult patients admitted to the Emergency Department of University Hospital Split between March 2020 and January 2021. Patients were classified into three groups: recent COVID-19 (<1 month), non-recent COVID-19 (1 to 12 months), and non-COVID-19. RESULTS: Fifty (47.2%) of 106 patients had a history of SARS-CoV-2 infection (23 patients in the recent COVID-19 and 27 in non-recent COVID-19 group). The three groups did not significantly differ in demographic and clinical parameters, including the location of deep venous thrombosis. The recent COVID-19 group had significantly higher neutrophils and CRP levels, and significantly lower prothrombin than the other two groups. CONCLUSION: Our results confirm the role of elevated inflammatory and coagulation response in DVT development in the first month after the infection, but not in non-recent COVID-19 or non-COVID-19 patients.

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels.

Thyroglobulin (Tg) is an iodoglycoprotein produced by thyroid follicular cells which acts as an essential substrate for thyroid hormone synthesis. To date, only one genome-wide association study (GWAS) of plasma Tg levels has been performed by our research group. Utilizing recent advancements in computation and modeling, we apply a Bayesian approach to the probabilistic inference of the genetic architecture of Tg. We fitted a Bayesian sparse linear mixed model (BSLMM) and a frequentist linear mixed model (LMM) of 7,289,083 variants in 1096 healthy European-ancestry participants of the Croatian Biobank. Meta-analysis with two independent cohorts (total n = 2109) identified 83 genome-wide significant single nucleotide polymorphisms (SNPs) within the ST6GAL1 gene (p<5×10-8). BSLMM revealed additional association signals on chromosomes 1, 8, 10, and 14. For ST6GAL1 and the newly uncovered genes, we provide physiological and pathophysiological explanations of how their expression could be associated with variations in plasma Tg levels. We found that the SNP-heritability of Tg is 17% and that 52% of this variation is due to a small number of 16 variants that have a major effect on Tg levels. Our results suggest that the genetic architecture of plasma Tg is not polygenic, but influenced by a few genes with major effects.

Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians.

Autoimmune thyroid diseases (AITD) are multifactorial endocrine diseases most frequently accompanied by Tg and TPO autoantibodies. Both antibodies have a higher prevalence in females and act under a strong genetic influence. To identify novel variants underlying thyroid antibody levels, we performed GWAS meta-analysis on the plasma levels of TgAb and TPOAb in three Croatian cohorts, as well as gender specific GWAS and a bivariate analysis. No significant association was detected with the level of TgAb and TPOAb in the meta-analysis of GWAS or bivariate results for all individuals. The bivariate analysis in females only revealed a genome-wide significant association for the locus near GRIN3A (rs4457391, P = 7.76 × 10-9). The same locus had borderline association with TPOAb levels in females (rs1935377, P = 8.58 × 10-8). In conclusion, we identified a novel gender specific locus associated with TgAb and TPOAb levels. Our findings provide a novel insight into genetic and gender differences associated with thyroid antibodies.

Thyroid hormone levels are associated with metabolic components: a cross-sectional study.

AIM: To analyze the association of thyroid function and hormone levels with metabolic syndrome (MetS) and its components. METHODS: This cross-sectional population-based study involved 2183 Croatian individuals with no history of thyroid disease, hypertension, diabetes, and hyperlipidemia. MetS was diagnosed according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. RESULTS: We found no association between thyroid function groups and the prevalence of MetS and its components. Clinically hypothyroid participants showed significantly higher triceps skinfold measurements than subclinically hypothyroid and euthyroid participants. Furthermore, clinically hypothyroid participants had higher abdominal skinfold thickness than subclinically hypothyroid participants. Otherwise, suprailiac and abdominal skinfold measurements were higher in the subclinically and clinically hyperthyroid group of participants compared with euthyroid and subclinically hypothyroid participants. A strong positive association of thyroid-stimulating hormone (TSH) and strong negative association of free triiodothyronine (fT3) and free thyroxine (fT4) levels with HOMA-IR and cholesterol levels were found. Furthermore, the fT4 level also showed a strong negative association with HDL and triceps skinfold thickness. CONCLUSIONS: This study supports the standing that TSH, fT3, and fT4 levels are important variables to determine the association of thyroid function with MetS.

Genome-wide association meta-analysis for total thyroid hormone levels in Croatian population.

Thyroid hormones (THs) are key regulators of cellular growth, development, and metabolism. The thyroid gland secretes two THs, thyroxine (T4) and triiodothyronine (T3), into the plasma where they are almost all bound reversibly to plasma proteins. Free forms of THs are metabolically active, however, they represent a very small fraction of total TH levels. No genome-wide studies have been performed to date on total TH levels, comprising of protein-bound and free forms of THs. To detect genetic variants associated with total TH levels, we carried out the first GWAS meta-analysis of total T4 levels in 1121 individuals from two Croatian cohorts (Split and Korcula). We also performed GWAS analyses of total T3 levels in 577 individuals and T3/T4 ratio in 571 individuals from the Split cohort. The top association in GWAS meta-analysis of total T4 was detected for an intronic variant within SLC22A9 gene (rs12282281, P = 4.00 × 10-7). Within the same region, a genome-wide significant variant (rs11822642, P = 2.50 × 10-8) for the T3/T4 ratio was identified. SLC22A9 encodes for an organic anion transporter protein expressed predominantly in the liver and belongs to the superfamily of solute carriers (SLC), a large group of transport membrane proteins. The transport of THs across the plasma membrane in peripheral tissues is facilitated by the membrane proteins, and all TH transport proteins known to date belong to the same SLC superfamily as SLC22A9. These results suggest a potential role for SLC22A9 as a novel transporter protein of THs.

The effect of multiple nutrients on plasma parathyroid hormone level in healthy individuals.

Although the effect of isolated nutrients on plasma parathyroid hormone (PTH) is somewhat familiar, the effect of multiple nutrients on plasma PTH level has not yet been studied. The aim of this study was to identify groups of food items that are associated with the plasma PTH level in healthy individuals. This cross-sectional study enrolled 1180 healthy individuals from Croatia with plasma PTH levels inside the referent values. A food frequency questionnaire containing 58 food items was completed to evaluate the dietary intake. We used principal component analysis to reduce food items into dietary groups, followed by linear regression analysis to test the association between dietary groups and the level of PTH. The results indicate that different sorts of vegetables (p = .006), sausages, salami, mushrooms, eggs (p = .033), as well as white bread (p = .009) are associated with the increase, while bran bread (p = .009) is associated with the decreased plasma PTH level.

Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level.

BACKGROUND: Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Although serum PTH level is mostly accounted by genetic factors, genetic background underlying PTH level is insufficiently known. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels. METHODS: We performed GWAS meta-analysis within two genetically isolated Croatian populations followed by replication analysis in a Croatian mainland population and we also combined results across all three analyzed populations. The analyses included 2596 individuals. A total of 7,411,206 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. In addition, a sex-specific GWAS meta-analyses were performed. RESULTS: Polymorphisms with the lowest P-values were located on chromosome 4 approximately 84 kb of the 5' of RASGEF1B gene. The most significant SNP was rs11099476 (P = 1.15 × 10-8). Sex-specific analysis identified genome-wide significant association of the variant rs77178854, located within DPP10 gene in females only (P = 2.21 × 10- 9). There were no genome-wide significant findings in the meta-analysis of males. CONCLUSIONS: We identified two biologically plausible novel loci associated with PTH levels, providing us with further insights into the genetics of this complex trait.

Parents' Beliefs about Medicines and Their Influence on Inhaled Corticosteroid Adherence in Children with Asthma.

The most widespread chronic condition observed amid children globally is asthma. Only half of children with asthma adhere to their prescribed inhaled corticosteroids (ICS) therapy. Parents' emotions and perspectives regarding asthma have an impact on inhalation corticosteroid adherence. The participants in this study were 148 parents of children with asthma, with the aim to redintegrate their beliefs about medicines in general and specifically of ICS and the impact on ICS adherence in children with asthma. Children were mostly male (66.9%), older than five years (58.8%), parents were female, mean age 38, employed, and with a history of consumption of some form of corticosteroids. Parents' answers show that 50% of them disagreed with the statement that medicines are addictive, and 90% agree that medicine helps many to live better. A percentage of 77.7% of parents acknowledge that their child's health relies on inhaled corticosteroids (ICS), and 86.5% of parents agree that these medications safeguard their child from worsening health. Most of the parents (93.2%) adhere to the guidelines and instructions of the doctor. In summary, parents who hold the belief that medicines are neither overused nor harmful tend to exhibit a higher adherence. Furthermore, those with elevated adherence levels express lower levels of concern regarding the use of inhaled corticosteroids (ICS) in their children's asthma therapy.

Communicating Arteries and Leptomeningeal Collaterals: A Synergistic but Independent Effect on Patient Outcomes after Stroke.

The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of the Willis' circle supply antegrade blood flow, while pial (leptomeningeal) arteries direct blood via retrograde flow. The aim of our retrospective study was to investigate the relationship between both collateral systems, computed tomography perfusion (CTP) values, and functional outcomes in acute stroke patients. Overall, 158 patients with anterior circulation stroke who underwent mechanical thrombectomy were included in the study. We analyzed the presence of communicating arteries and leptomeningeal arteries on computed tomography angiography. Patients were divided into three groups according to their collateral status. The main outcomes were the rate of functional independence 3 months after stroke (modified Rankin scale score, mRS) and mortality rate. Our study suggests that the collateral status, as indicated by the three groups (unfavorable, intermediate, and favorable), is linked to CT perfusion parameters, potential recuperation ratio, and stroke outcomes. Patients with favorable collateral status exhibited smaller core infarct and penumbra volumes, higher mismatch ratios, better potential for recuperation, and improved functional outcomes compared to patients with unfavorable or intermediate collateral status.

Trial of a Novel Oral Cannabinoid Formulation in Patients with Hypertension: A Double-Blind, Placebo-Controlled Pharmacogenetic Study.

Cannabidiol (CBD) is a non-psychoactive cannabinoid, and available evidence suggests potential efficacy in the treatment of many disorders. DehydraTECH™2.0 CBD is a patented capsule formulation that improves the bioabsorption of CBD. We sought to compare the effects of CBD and DehydraTECH™2.0 CBD based on polymorphisms in CYP P450 genes and investigate the effects of a single CBD dose on blood pressure. In a randomized and double-blinded order, 12 females and 12 males with reported hypertension were given either placebo capsules or DehydraTECH™2.0 CBD (300 mg of CBD, each). Blood pressure and heart rate were measured during 3 h, and blood and urine samples were collected. In the first 20 min following the dose, there was a greater reduction in diastolic blood pressure (p = 0.025) and mean arterial pressure MAP (p = 0.056) with DehydraTECH™2.0 CBD, which was probably due to its greater CBD bioavailability. In the CYP2C9*2*3 enzyme, subjects with the poor metabolizer (PM) phenotype had higher plasma CBD concentrations. Both CYP2C19*2 (p = 0.037) and CYP2C19*17 (p = 0.022) were negatively associated with urinary CBD levels (beta = -0.489 for CYP2C19*2 and beta = -0.494 for CYP2C19*17). Further research is required to establish the impact of CYP P450 enzymes and the identification of metabolizer phenotype for the optimization of CBD formulations.

Perception of Illness and Fear of Inhaled Corticosteroid Use among Parents of Children with Asthma.

The most prevalent children's chronic disease worldwide is asthma which has notable negative impacts on patients' and parent's quality of life. Daily inhaled corticosteroids (ICS) therapy is a preferred controller choice. This study was conducted on 148 parents of asthmatic children to establish parents' perception of illness and fear of inhaled corticosteroids using B-IPQ and TOPICOP questionnaires. Children were in the majority male (66.9%), older than five years (58.8%), with comorbidities, and family history of atopy. Parents were female, with a mean age of 38, employed, and with a history of some form of corticosteroid use. Most parents were not afraid of ICS usage (71.6%). Unemployed parents and parents who had no medical education had a statistically significantly higher fear of using ICS (p = 0.002, p = 0.03). A child's illness affects the parents' lives and parents who are afraid of using ICS react more emotionally to the child's illness. Better understanding and less concerned about child's disease are parents of children with controlled asthma. The parents' perspective of children's asthma will affect the duration and dose of ICS treatment they will give to their children and directly influence the level of asthma control.

Attitudes and factors that affect Croatian nursing students' choice of thesis type: A cross-sectional study.

BACKGROUND: Research in nursing, as in other biomedical professions, is of paramount importance. Nursing students are required to attend research methodology courses during their studies. However, nursing research is lagging behind other biomedical fields. OBJECTIVES: This study aimed to examine attitudes and factors that influence the choice of thesis type (original research versus essay-type literature review) among Croatian nursing students. METHODS: This cross-sectional study included nursing students from 8 health sciences studies in Croatia in the 2020/2021 academic year. Data were collected using the Students' Attitudes Toward Research (SAR) questionnaire and questions assessing potential barriers toward research. RESULTS: There were 912 students (25 % response rate) included in the study. In the regression analysis of the total sample, mentor encouragement (ß 0.200; P < 0.001), knowledge (ß 0.137; P = 0.011), and sense of ability to conduct research (ß 0.191; P < 0.001) were positively associated with the SAR score, while the expectation that a research-based thesis will extend the study duration was negatively associated with the SAR score (ß -0.124; P = 0.036). Among bachelor's students, the sense of ability to conduct research (ß 0.255; P < 0.001) was positively associated, while the expectation that a research-based thesis will extend the study duration was negatively associated with the SAR score (ß -0.157; P = 0.053). Among master's students, mentor encouragement (ß 0.415; P < 0.001), knowledge (ß 0.261; P < 0.001), and sense of ability to conduct research (ß 0.151; P = 0.045) were positively associated with the SAR score. A higher SAR score was associated with a higher likelihood of selecting a research thesis (OR [95 % CI]; P: 1.026 [1.014-1.038]; P < 0.001). CONCLUSIONS: Our study revealed modifiable factors associated with positive attitudes toward scientific research and preference for a research-based thesis among nursing students. Policy-makers should consider our results and change nursing studies' curricula and mentors should encourage students to engage in research and conduct research-based thesis even if there are other thesis options available.

Parental Traits Associated with Adherence to the Mediterranean Diet in Children and Adolescents in Croatia: A Cross-Sectional Study.

The Mediterranean diet (MD) is known to be one of the healthiest dietary patterns. Despite the significance of a healthful diet during the early stage of life, data for young individuals indicate that nutrition problems are common. This cross-sectional study aimed to determine parental factors associated with MD adherence in children and adolescents living in the Mediterranean region in Croatia. In total, 2623 children aged 2 to 18 years and their parents participated in this study. Data were collected during the period from September 2021 to February 2022 by using an anonymous questionnaire. We used KIDMED and MEDAS questionnaires for assessing MD adherence in young individuals and their parents, respectively. To assess the association of children's MD adherence categories with the parental predictors, we performed multivariate multinomial logistic regression. Results showed that the children of parents with a low MD adherence are much more likely to have poor MD adherence than good (OR = 47.54 (95% C.I 18.24, 123.87), p < 0.001) or average (OR = 5.64 (95% C.I 3.70, 8.6), p < 0.001) MD adherence. Further, children of fathers with higher BMI (OR = 1.035 (95% C.I 1.0, 1.071)) and those who do not live with both parents (OR = 1.703 (95% C.I 0.994, 2.916), p = 0.053) are more likely to have poor MD adherence than good MD adherence. These results indicate that interventions focusing on enhancing the quality of both parents' diets could effectively improve their children's eating habits.

Adherence to the Mediterranean Diet among Children and Youth in the Mediterranean Region in Croatia: A Comparative Study.

The Mediterranean diet (MD) is considered one of the healthiest dietary patterns. The aim of this study was to assess MD adherence in children and youth living in the Mediterranean region in Croatia and evaluate the differences in adherence to the MD among different educational stages. In total, 2722 individuals aged 2 to 24 years were enrolled in this study. Subjects were divided into different groups according to the Croatian educational system. Mediterranean Diet Quality Index (KIDMED) was used to assess adherence to the MD. In the total sample, the adherence to the MD was poor in 19.2%, average in 60.8%, and good in 20.1% of the study participants. The prevalence rate of poor adherence to the MD increased with higher educational stage, i.e., the highest prevalence rate of poor MD adherence was observed for college students (39.3%). Children having a higher number of snacks on days-off, those with lower physical activity, and not having breakfast together with a family are more likely to have poor MD adherence, while children having a higher number of snacks on working days are less likely to have a poor MD. The results of this study showed low adherence to the principles of the MD, confirming the need for improvement of adherence to the MD pattern in the studied population.

Rare and common genetic variations in the Keap1/Nrf2 antioxidant response pathway impact thyroglobulin gene expression and circulating levels, respectively.

Nuclear factor, erythroid 2-like 2 (Nrf2) is a transcription factor that has been gaining attention in the field of pharmacology and especially in the chemoprevention of diseases such as cancer, metabolic and neurodegenerative diseases, etc. This is because natural compounds such as sulforaphane, which is found in broccoli sprout extracts, can activate Nrf2. The repertoire of the roles of Nrf2 is ever increasing; besides its traditional antioxidant and cytoprotective effects, Nrf2 can have other functions as a transcription factor. We have recently shown that Nrf2 directly regulates the expression of thyroglobulin (Tg), which is the most abundant thyroidal protein and the precursor of thyroid hormones. Two functional binding sites for Nrf2 (antioxidant response elements, AREs) were identified in the regulatory region of the TG gene. Interestingly, we then observed that one of these AREs harbors a rare single-nucleotide polymorphism (SNP). Also recently, we performed the first genome-wide association study (GWAS) for common SNPs that impact the circulating levels of Tg. Based on these investigations, we were triggered (i) to investigate whether common SNPs in the Nrf2 pathway correlate with circulating Tg levels; and (ii) to examine whether the rare SNP in one of the TG regulatory AREs may affect gene expression. To address the first question, we analyzed GWAS data from a general population and its two subpopulations, one with thyroid disease and/or abnormal thyroid function tests and the other without, in which circulating Tg levels had been measured. Statistically significant associations with Tg levels were observed in the genes encoding Nrf2 and Keap1, including, notably, a known functional SNP in the promoter of the gene encoding Nrf2. Regarding the rare SNP (rs778940395) in the proximal ARE of the TG enhancer, luciferase reporter gene expression studies in PCCL3 rat thyroid follicular cells showed that this SNP abrogated the basal and sulforaphane- or TSH-induced luciferase activity, behaving as a complete loss-of-function mutation. Thus, both rare and common genetic variation in the Keap1/Nrf2 pathway can impact TG expression and Tg circulating levels, respectively.

Genome-Wide Analysis Identifies Two Susceptibility Loci for Positive Thyroid Peroxidase and Thyroglobulin Antibodies.

INTRODUCTION: Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indicator of autoimmune thyroid disease. TPOAb and TgAb are under strong genetic influence; however, genetic factors that determine thyroid antibody positivity are largely unknown. MATERIALS AND METHODS: To identify novel loci associated with TPOAb and/or TgAb positivity, we performed a genome-wide meta-analysis in a total of 2613 individuals from Croatia. Participants with elevated plasma TPOAb and/or TgAb were defined as cases (N = 619) and those with TPOAb and TgAb within reference values were defined as controls (N = 1994). RESULTS: We identified 2 novel loci, of which 1 is located within the YES1 gene (rs77284350, P = 1.50 × 10-8), and the other resides within the IRF8 gene (rs16939945, P = 5.04 × 10-8). CONCLUSIONS: Although the observed variants were associated with TPOAb and TgAb positivity for the first time, both YES1 and IRF8 were previously linked to susceptibility to other autoimmune diseases, and represent plausible biological candidates. This study adds to the knowledge of genetics underlying thyroid antibodies and provides a good basis for further research.

Low ERCC1 expression is a good predictive marker in lung adenocarcinoma patients receiving chemotherapy based on platinum in all TNM stages - a single-center study.

BACKGROUND: High ERCC1 expression is thought to be related with resistance to chemotherapy based on platinum. The aim of this study was to present our institutional observations regarding to the association of ERCC1 and overall survival (OS) of the lung adenocarcinoma patients who received chemotherapy based on platinum. MATERIAL/METHODS: A total of 253 lung adenocarcinoma patients in all TNM stages were retrospectively investigated. The diagnosis was based on small biopsy samples obtained during bronchoscopy. Depending on the TNM stage of the disease and clinical condition, patients received only the chemotherapy based on platinum, or in combination with radiotherapy or surgery. Tissue sample for ERCC1 immunohistochemical analysis was sufficient in 129 patients. Low from high ERCC1 expression was separated by the semi-quantitative H-score median. RESULTS: High ERCC1 expression was found in 47.3% patients, and was correlated with higher TNM (p = 0.021), tumor enlargement (p = 0.002), positive lymph nodes (p = 0.001), positive distant metastasis (p = 0.005), and higher relative risk of death (p < 0.001). Furthermore, significance association was observed for low ERCC1 expression and better performance status (ECOG) (p = 0.023). Longer OS was strongly associated with a low ERCC1 expression, not only in the group of patients in TNM stage I-III, who were treated with combination of chemotherapy with surgery or radiotherapy (p = 0.002), but also in the group of patients in TNM stage IV who received only chemotherapy based on platinum (p < 0.001), compared with the patients in the same TNM stage and high ERCC1 expression. CONCLUSIONS: ERCC1 expression in lung adenocarcinoma is a useful prognostic marker and moreover, a useful predictive marker in patients receiving chemotherapy based on platinum in all stages of the disease.

Genetic Variants in the ST6GAL1 Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals.

Background: Thyroglobulin (Tg) is a 660 kDa iodoglycoprotein that serves as a scaffold for thyroid hormone synthesis. Although a twin study showed that variability of serum Tg levels has a substantial genetic basis, no genome-wide association study (GWAS) of serum/plasma Tg levels has been performed to date. The aim of this study was to identify genetic variants associated with plasma Tg levels among healthy individuals. Methods: A GWAS was conducted on two Croatian cohorts, and a combined analysis was performed. The analyses included 1094 individuals. A total of 7,597,379 variants, imputed using the 1000 Genomes reference panel, were analyzed for association. GWAS was performed under an additive model, controlling for age, sex, and relatedness within each data set. Combined analysis was conducted using the inverse-variance fixed-effects method. Results: Sixteen variants located on chromosome 3, within the ST6GAL1 gene, reached genome-wide significance. The lead SNP was rs4012172 ( \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$p = 1.29 \times {10^{ - 10}}$$ \end{document} ), which explained 3.19% of the variance in Tg levels. ST6GAL1 belongs to the sialyltransferase protein family, which has a fundamental role in the synthesis of specific sialylated structures on various glycoproteins, including Tg. It is known that only immature Tg (poorly sialylated or desialylated) can be transferred to the bloodstream. Conclusions: A highly biologically plausible locus was identified that could have a role in the regulation of plasma Tg levels in healthy individuals.