Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity.

Fatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann-Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood.

Therapeutic drug monitoring of monoclonal antibodies in chronic inflammatory diseases: A snapshot of laboratories and applications across Europe.

The European Cooperation in Science and Technology (COST) action ENOTTA (The European Network on Optimising Treatment with Therapeutic Antibodies in chronic inflammatory diseases) was launched in 2022. To pave the way for harmonization of analytical methods for quantitation of serum levels of therapeutic antibodies in research and clinical settings, ENOTTA recently performed an online survey mapping laboratories in the field. The survey, which contained 30 questions surrounding therapeutic drug monitoring of relevant drugs and anti-drug antibodies, was distributed via the ENOTTA and European Federation of Clinical Chemistry and Laboratory networks. Among 63 respondents across Europe, 45 reported analytical activity, with a range of utilized methods. Future engagement of as many sites as possible will enable comparison of methodologies and facilitate progress in the field.

Analysis of redox status and HDL subclasses in patients with lymphoma and the associations with FDG-PET/CT findings.

Newer research points to alterations in the plasma redox status and the HDL subclass distributions in cancer. We aimed to assess the redox status and the HDL subclass distributions, lipids, and inflammatory markers in lymphoma patients in order to determine whether they were correlated with changes in FDG-PET/CT scans. At the beginning of this study, redox status, HDL subclasses, lipids, and inflammation biomarkers were determined in 58 patients with lymphoma (Hodgkin lymphoma, n=11 and non-Hodgkin lymphoma, n=47), and these same measurements were reassessed during their ensuing treatment (in 25 patients). Initially, the total oxidation status (TOS), the prooxidant-antioxidant balance (PAB), the OS index (OSI), the total protein sulfhydryl groups (SH-groups), and the advanced oxidation protein products (AOPP) were significantly higher in lymphoma patients as compared to healthy subjects, but the total antioxidant status (TAS) was significantly reduced. The PAB had a strong correlation with the CRP and interleukin-6 (rho=0.726, p<0.001; rho=0.386, p=0.003). The correlations between these parameters and the maximum standardized uptake values (SUVmax) were: PAB, rho=0.335 and p=0.010; SH-groups, rho=0.265 and p=0.044; CRP, rho=0.391 and p=0.002; HDL3b, rho=0.283 and p=0.031; HDL2b, rho= -0.294 and p=0.025; and HDL size, rho= -0.295 and p=0.024. The reductions in SUVmax between two follow-up points were associated with increases in the OSI, TOS, and SH-groups, as well as a reduction in the PAB and TAS. In conclusion, the redox parameters in patients with lymphoma were consistent with FDG-PET/CT findings. Targeting the redox status parameters and the HDL subclasses could be potential strategies in the molecular fight against lymphoma.

The predictive role of biochemical markers on outcomes of severe COVID-19 patients admitted to intensive care unit.

Background: The pandemic of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) is a multi-system disease caused by a diffuse systemic process involving a complex interaction of the inflammatory, immunological and coagulative cascades. This study aims to identify the most effective biomarkers to predict poor outcome in intensive care unit (ICU) patients with severe COVID-19 disease. Methods: A single-centre retrospective observational study enrolled 69 deceased and 20 recovered patients treated in the ICU of the General Hospital Gradiska in the period from March 1, 2021. until April 1, 2022. We evaluated the leukocytes (WBC), lymphocytes (LYM), neutrophils (NEU), platelets (PLT), haemoglobin, neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). In addition, we evaluated the IL-6, ferritin, CRP, D-dimer, magnesium, bilirubin and lactate dehydrogenase.

Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients.

The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.

Pharmacotherapy literacy level and predictors of low literacy among diabetes mellitus type 2 patients in Serbia.

BACKGROUND: Pharmacotherapy literacy (PTHL) is a specific ability to safely access, appraise and understand the available information concerning medication and to calculate and act accordingly. The concept of PTHL is mostly unknown for the majority of diabetes mellitus type 2 (DMT2) patients in Serbia. With diabetes being one of the major public health problems in Serbia with a prevalence of 9.1%, this two-study research aims at constructing performance-based instrument and estimating the prevalence of PTHL levels and identification of predictors of low PTHL scores in patients with DMT2. METHODS: Multistage study was performed to adapt the existing performance-based instrument (PTHL-SR) into specific questionnaire for DMT2 population (PTHL-DM instrument). PTHL levels were assessed through cross-sectional study categorising patients into groups of low, medium, and high PTHL levels. We considered 19 predictors for low PTHL scores, from sociodemographic characteristics, health behaviours and health characteristics, access to health-related information and empowerment-related indicators. Univariate and multivariate logistic regression analyses were used to determine independent predictors of low PTHL. RESULTS: The final 15-item PTHL-DM instrument proved to have satisfactory reliability (KR20 = 0.475) and internal reliability [ICC for the whole instrument was 0.97 with 95% confidence intervals (0.95-0.99)]. Positive correlation (rho = 0.69) between PTHL-DM score (15 questions) and the total PTHL-SR score (14 questions) was also observed. It was demonstrated that the majority of 350 patients had low PTHL (62%), and only 5% high PTHL level. Mean score on PTHL-DM was 7.8 ± 2.3. Probability of low PTHL increased among smokers, patients with low interest in health and those who estimated their health as bad. Patients who used pharmacists as sourse of information were less likely to be pharmacotherapy illiterate. Combined therapy with insulin and Oral Hypoglycemic Agents was associated with higher PTHL. CONCLUSIONS: Our data indicate that specific PTHL-DM tool is objective, valid, and reliable. It was found that low level of PTHL prevailed among DMT2 patients. Medication literacy is influenced by age, residence, education, and family status. Patients with better health literacy also reported better health behaviours. Different patient empowerment programs and approaches aimed at raising PTHL would be essential to improve self-management and control of this widespread chronic disease in Serbia.

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction.

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.

The Prospect of Genomic, Transcriptomic, Epigenetic and Metabolomic Biomarkers for The Personalized Prevention of Type 2 Diabetes and Cardiovascular Diseases.

Cardiometabolic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular disease (CVD), are a great health concern. The strategies aimed to increase awareness and prevention, in conjunction with timely diagnosis and optimal management of these conditions, represent the main lines of action to improve life expectancy and quality. In recent years, the introduction of innovative therapies for the treatment of DM and CVD has provided new hope for high-risk patients. Yet, the implementation of preventive measures in achieving cardiometabolic health is far from successful and requires further improvement. The development of cardiometabolic disorders is a complex, multifactorial process involving several metabolic pathways as well as genetic and environmental factors. Decreasing cumulative exposure during the entire life course and timely recognition and targeting of potential riskenhancing factors could pave the way toward more successful prevention of cardiometabolic disorders. Nowadays, in the era of "omics" technologies, it is possible to identify novel biomarkers and therapeutic targets, which offers the possibility to apply an individualized approach for each patient. This review will discuss potential applications of genomic, transcriptomic, epigenetic and metabolomic biomarkers for the personalized prevention of cardiometabolic diseases.

Telomere-telomerase system status in patients with acute myocardial infarction with ST-segment elevation - relationship with oxidative stress.

Introduction: Telomeres are protective chromosomal ends. Short telomeres are a proven biomarker of biological aging. We aimed to find an association of telomere length and telomerase activity in circulating leukocytes and thromboaspirates of patients with acute myocardial infarction. Furthermore, association of the telomere-telomerase system with oxidative stress markers (as common risk factors for coronary artery disease (CAD)) was tested. Material and methods: Patients were selected from the patients admitted to the intensive care unit with acute myocardial infarction with ST-segment elevation (STEMI), with the following inclusion criteria - STEMI patients between 18 and 80 years old of both genders and candidates for primary percutaneous coronary intervention, with infarction pain present for a maximum of 12 h. In all the patients leukocyte telomere length, telomerase activity and scores related to oxidative-stress status (Protective, Damage and OXY) were evaluated. Results: Patients were divided into different groups: with stable angina pectoris (AP) (n = 22), acute myocardial infarction with: STEMI (n = 93), non-obstructive coronary arteries (MINOCA) (n = 7), blood vessel rupture (n = 6) at three time points, and compared to the group of 84 healthy subjects. Telomerase activity was significantly higher in all CAD sub-groups compared to the control group (AP = 0.373 (0.355-0.386), STEMI = 0.375 (0.349-0.395), MINOCA = 0.391 (0.366-0.401), blood vessel rupture = 0.360 (0.352-0.385) vs. CG = 0.069 (0.061-0.081), p < 0.001), while telomeres were significantly shorter in STEMI, MINOCA and blood vessel rupture groups compared to the control group (STEMI = 1.179 (0.931-1.376), MINOCA = 1.026 (0.951-1.070), blood vessel rupture = 1.089 (0.842-1.173) vs. CG = 1.329 (1.096-1.624), p = 0.030]. Values of OXY score were significantly higher in STEMI and MINOCA patients compared to the control group and AP patients (5.83 (4.55-7.54) and 10.28 (9.19-10.72) vs. 4.94 (3.29-6.18) and 4.18 (2.58-4.86), p < 0.001). Longer telomeres and higher telomerase activity were found in thromboaspirates, compared to the peripheral blood leukocytes in the same patients (1.25 (1.01-1.84) vs. 1.18 (0.909-1.516), p = 0.036; and 0.366 (0.367-0.379) vs. 0.366 (0.367-0.379), p < 0.001, respectively). In addition, telomere length and telomerase activity had good diagnostic ability to separate STEMI patients from healthy persons. Conclusions: Leukocyte telomere length and telomerase activity can differentiate CAD patients from healthy persons, and relate CAD to oxidative stress.

Predictors of Inadequate Health Literacy among Patients with Type 2 Diabetes Mellitus: Assessment with Different Self-Reported Instruments.

INTRODUCTION: Obtaining, understanding, interpreting, and acting on health information enables people with diabetes to engage and make health decisions in various contexts. Hence, inadequate health literacy (HL) could pose a problem in making self-care decisions and in self-management for diabetes. By applying multidimensional instruments to assess HL, it is possible to differentiate domains of functional, communicative, and critical HL. OBJECTIVES: Primarily, this study aimed to measure the prevalence of inadequate HL among type 2 diabetes mellitus patients and to analyze the predictors influencing health literacy levels. Secondly, we analyzed if different self-reported measures, unidimensional instruments (Brief Health Literacy instruments (BRIEF-4 and abbreviated version BRIEF-3), and multidimensional instruments (Functional, Communicative and Critical health literacy instrument (FCCHL)) have the same findings. METHODS: The cross-sectional study was conducted within one primary care institution in Serbia between March and September 2021. Data were collected through Serbian versions of BRIEF-4, BRIEF-3, and FCCHL-SR12. A chi-square test, Fisher's exact test, and simple logistic regression were used to measure the association between the associated factors and health literacy level. Multivariate analyses were performed with significant predictors from univariate analyses. RESULTS: Overall, 350 patients participated in the study. They were primarily males (55.4%) and had a mean age of 61.5 years (SD = 10.5), ranging from 31 to 82 years. The prevalence of inadequate HL was estimated to be 42.2% (FCCHL-SR12), 36.9% (BRIEF-3) and 33.8% (BRIEF-4). There are variations in the assessment of marginal and adequate HL by different instruments. The highest association was shown between BRIEF-3 and total FCCHL-SR12 score (0.204, p < 0.01). The total FCCHL-SR12 score correlates better with the abbreviated BRIEF instrument (BRIEF-3) than with BRIEF-4 (0.190, p < 0.01). All instruments indicated the highest levels for the communicative HL domain and the lowest for the functional HL domain with significant difference in functional HL between the functional HL of FCCHL-SR12 and both BRIEF-3 and BRIEF-4 (p = 0.006 and 0.008, respectively). Depending on applied instruments, we identified several variables (sociodemographic, access to health-related information, empowerment-related indicators, type of therapy, and frequency of drug administration) that could significantly predict inadequate HL. Probability of inadequate HL increased with older age, fewer children, lower education level, and higher consumption of alcohol. Only high education was associated with a lower probability of inadequate HL for all three instruments. CONCLUSIONS: The results we obtained indicate that patients in our study may have been more functionally illiterate, but differences between functional level could be observed if assessed by unidimensional and multidimensional instruments. The proportion of patients with inadequate HL is approximately similar as assessed by all three instruments. According to the association between HL and educational level in DMT2 patients we should investigate methods of further improvement.

SMART Pharmacists Serving the New Needs of the Post-COVID Patients, Leaving No-One Behind.

This study aims to demonstrate the improvements in clinical symptoms in patients with post-COVID syndrome after a community pharmacy-based intervention in Serbia. The Pharmaceutical Chamber of Serbia ("Chamber") invited pharmacists to deliver post-COVID patient care counselling, supported by the SMART Pharmacist Program, offering education and guidance. Present symptoms, duration and patient self-reported severity of symptoms on a scale of 1-5 on the first visit were recorded. After the counselling and proposed self-medication treatment, the time of the follow-up visit and the severity of the recorded symptoms were also recorded. The prospective data collection lasted from December 2021 to September 2022. In total, 871 patients with post-COVID symptoms were included in the study, served by 53 pharmacists. The most frequently reported post-COVID symptoms coincided with the literature, mostly related to the respiratory system (51.2%), immunity status (32.2%), fatigue and exhaustion (30.7%), skin, hair and nails (27.4%) and cognitive functions (27.9%). A total of 26.5% of patients were referred to their family physician (general practitioner), and 69.5% returned to the pharmacist for a follow-up visit. On the first visit, the median severity of patients' symptoms was three, while on the second visit it dropped to one. The pharmacists' intervention led to a significant improvement in the post-COVID patients' condition.

Treatment of vascular non-iatrogenic injuries of upper and lower extremities in tertiary vascular center.

BACKGROUND: The purpose of this study was to examine demographic and baseline characteristics of patients with vascular injuries of extremities and to define the most relevant factors which influenced an early outcome, as well as limb salvage after the management of vascular trauma. METHODS: This study used the database that included 395 patients with peripheral arterial injuries, who were treated in the tertiary vascular university center in the period between 2005-2020. Exclusion criteria were isolated thoracic, abdominal and neck injuries as well as iatrogenic injuries and injuries of intravenous addicts. Univariate binary logistic regression analysis and multiple logistic regression were used to determine risk factors for lomb loss (after vascular reconstruction) or mortality. Decision to perform primary amputation (without vascular reconstruction) was based on surgeons' preference and experience. RESULTS: Out of 395 vascular injuries treated in the period 2005-2020, 210 (53.2%) presented with non-iatrogenic vascular injuries of upper and lower extremities were analyzed. According to the univariate regression analysis, hemorrhage as the main clinical manifestation on admission (P=0.035) and early reintervention (P=0.048) increased, while an early patency of repaired artery (0.010) significantly decreased a 30-day amputation rate. Multivariate logistic regression analysis of these three variables showed that only early patency of repaired artery significantly decreased the early amputation rate (P=0.009). CONCLUSIONS: Based on presented experience, the patency of vascular reconstruction plays a crucial role in limb salvage in patients with non-iatrogenic peripheral vascular injuries. All factors that might influence the patency should be in focus of improvement.

Association of Adiponectin Receptors with Metabolic and Immune Homeostasis Parameters in Colorectal Cancer: In Silico Analysis and Observational Findings.

Adiponectin (ADIPOQ) as both a regulator of metabolic homeostasis and a protein involved in immune response might be of particular interest to contemporary laboratory medicine, especially in terms of minimally invasive diagnostics. The diverse roles of ADIPOQ with regard to the immune and metabolic aspects of colorectal carcinogenesis have been proposed. However, the expression of its receptors ADIPOR1 and ADIPOR2 is scarcely explored in peripheral blood mononuclear cells (PBMCs). Moreover, ADIPORs' relationships with the immune response mediator TNF-α have not been previously investigated in the PBMCs of CRC patients. This study used both in silico and observational case-control analyses with the aim of exploring the association of ADIPOR gene expression and ADIPOQ single nucleotide polymorphisms (SNPs) with the inflammatory marker TNF-α and lipid status parameters in patients with CRC. Publicly available transcriptomic datasets (GSE47756, GSE44076) obtained from analyses of monocytes and CRC tissue samples were employed for the in silico evaluation of ADIPORs' specific genetic traits. GSE47756 and GSE44076 datasets were processed with GSEA software to provide a genetic fingertip of different signaling pathways associated with ADIPORs' mRNA levels. The case-control aspect of the study included the PBMC samples of 73 patients diagnosed with CRC and 80 healthy volunteers. The PCR method was carried out for the PBMC gene expression analysis (ADIPOR1, ADIPOR2, TNF-α mRNA levels) and for the subjects' genotyping (ADIPOQ rs266729, ADIPOR1 rs7539542). GSEA showed significant associations of ADIPOR mRNA expression with gene sets related to metabolic and immune homeostasis in both datasets. The case-control study revealed the association of ADIPOR1 rs7539542 with reduced lipid status parameters in CRC. In addition, PBMC ADIPOR1 mRNA levels decreased in CRC (p < 0.001), whereas ADIPOR2 mRNA did not differ between the groups (p = 0.442). A reduction in PBMC TNF-α mRNA levels was noted in CRC (p < 0.05). Our results indicate that ADIPOR1 and ADIPOR2 play a significant role in the alteration of both metabolic and immune homeostasis during the progression of CRC. For the first time, ADIPOR1 is shown to be a specific receptor for mediating ADIPOQ's effects in the PBMCs of CRC patients.

Alteration in Redox Status and Lipoprotein Profile in COVID-19 Patients with Mild, Moderate, and Severe Pneumonia.

Background: Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods: The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results: Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions: Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.

Cross-Cultural Adaptation and Validation of the Functional, Communicative and Critical Health Literacy Instrument (FCCHL-SR) for Diabetic Patients in Serbia.

Thoroughly validated instruments can provide a more accurate and reliable picture of how the instrument works and of the level of health literacy in people with type 2 diabetes mellitus (T2DM). The present work aimed at cross-cultural adaptation and validation of the Functional, Communicative and Critical Health Literacy Instrument (FCCHL) in patients with T2DM in Serbia. After translation and back-translation, views from an expert group, one cognitive interview study (n = 10) and one survey study (n = 130) were conducted among samples of diabetic patients. Item analysis, internal consistency, content validity, confirmatory factor analysis (CFA) and reliability testing were performed. When all 14 items were analyzed, loading factors were above 0.55, but without adequate model fit. After removing two items with the lowest loadings FHL1 and IHL2 the fit indexes indicated a reasonable normed χ2 (SB scaled χ2/df = 1.90). CFI was 0.916 with SRMR = 0.0676 and RMSEA = 0.0831. To determine internal consistency, Cronbach's alpha coefficient was 0.796 for the whole FCCHL-SR12. With only minor modifications compared to the English version, the 12-item FCCHL instrument is valid and reliable and can be used to measure health literacy among Serbian diabetic patients. However, future research on a larger population in Serbia is necessary for measuring the levels of HL and their relationship with other determinants in this country.

Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer.

Background: The aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods. Methods: We analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3). Results: The RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34-4.10 mIU/L, 11.3-20.6 pmol/L, 3.5-6.32 pmol/L and 0.21-0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade (5.26 vs. 5.02, p=0.005), the fifth decade (5.26 vs. 4.94, p=0.001), the sixth decade (5.26 vs. 4.87, p<0.001), the seventh decade (5.26 vs. 4.79, p<0.001) and the group older than 70 years old (5.26 vs. 4.55, p<0.001). Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups. Conclusions: The establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations.

Novel Pharmaceutical and Nutraceutical-Based Approaches for Cardiovascular Diseases Prevention Targeting Atherogenic Small Dense LDL.

Compelling evidence supports the causative link between increased levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (CVD) development. For that reason, the principal aim of primary and secondary cardiovascular prevention is to reach and sustain recommended LDL-C goals. Although there is a considerable body of evidence that shows that lowering LDL-C levels is directly associated with CVD risk reduction, recent data shows that the majority of patients across Europe cannot achieve their LDL-C targets. In attempting to address this matter, a new overarching concept of a lipid-lowering approach, comprising of even more intensive, much earlier and longer intervention to reduce LDL-C level, was recently proposed for high-risk patients. Another important concern is the residual risk for recurrent cardiovascular events despite optimal LDL-C reduction, suggesting that novel lipid biomarkers should also be considered as potential therapeutic targets. Among them, small dense LDL particles (sdLDL) seem to have the most significant potential for therapeutic modulation. This paper discusses the potential of traditional and emerging lipid-lowering approaches for cardiovascular prevention by targeting sdLDL particles.

Effects of Apnea, Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: Full-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined. RESULTS: PCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m2) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m2 when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026-7.912], p = 0.044). CONCLUSION: Statin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.

A Questionnaire for Rating Health-related Quality of Life.

BACKGROUND: Translations of instruments for measuring quality of life developed in certain, mostly more developed, parts of the world usually do not cover regionally specific aspects of health-related quality of life, even after transcultural validation. The aim of this study was to develop and validate a reliable questionnaire in Serbian, Croatian, Bosnian, and Montenegrin languages suitable for measuring health-related quality of life in adults. METHODS: The study was of a cross-sectional type, assessing the reliability and validity of a newly developed questionnaire for measuring health-related quality of life (HRQoL) in adults residing in western Balkan states (WB-HRQoL). It was conducted on a sample of 489 adults from Serbia, Croatia, Bosnia & Herzegovina, and Montenegro, with a mean age of 52.2±14.4 years and a male/female ratio of 195/294 (39.9%/60.1%). RESULT: The definitive version of the WB-HRQoL scale with 19 items showed very good reliability, with Cronbach's alpha 0.905. The scale was temporally stable, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis brought to the surface four domains of health-related quality of life, namely the physical, psychical, social, and environmental. CONCLUSION: The WB-HRQoL scale is a reliable and valid generic instrument for measuring HRQoL that takes into account the cultural specifics of the western Balkan region.