A perspective on muscle phenotyping in musculoskeletal research.

Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.

Difference in the Standard and Novel Lipid Profile Parameters Between Patients With Alzheimer's Disease and Vascular Dementia Stratified by the Degree of Cognitive Impairment.

Background: Lipids and lipoproteins are significantly involved in maintaining structural and functional components of the human brain and neurons, but their role in the development of Alzheimer's disease (AD) and vascular dementia (VD) remains unclear. Objective: The aim of the present study was to explore the differences in the standard and novel lipid profile parameters in patients with AD and VD, stratified by the degree of cognitive impairment (CI). Methods: Present study included 66 patients with AD, 50 patients with VD, and 60 control subjects. For an evaluation of the global cognitive function the Montreal Cognitive Assessment (MoCA) test was used. In order to distinguish patients with VD from those with AD the Hachinski ischemic score was used. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with the Kruskal Wallis test followed by the Mann-Whitney test or with ANOVA followed by the Tuckey posthoc test. Results: Results of the conducted study have found that the patients in AD group with moderate CI and patients in AD group with severe CI exhibited significantly lower levels of serum TC, TG, LDL-C, VLDL-C, Non- HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C and LDL-C/HDL-C compared to cognitively normal control subjects. Moreover, patients in VD group with severe and moderate CI had significantly lower level of TG compared to control group of subjects. Our results have also shown that patients in AD group with moderate CI had significantly lower level of TC, TG, LDL-C, Non-HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C compared to VD patients with moderate CI. In addition, patients in AD group with severe CI had significantly lower level of TC, LDL-C, Non-HDL-C and TC/HDL-C compared to VD patients with severe CI. Conclusion: The results of this study have shown dysregulation of lipid metabolism in AD and VD patients with different degree of CI. In both moderate and in severe CI, patients with AD had lower levels of majority of standard and novel lipid parameters compared to patients with VD. Further larger prospective studies are required to elucidate the accuracy of standard and novel lipid parameters in the assessment of different degree of CI in AD and VD.

The impact of type 2 diabetes duration on serum asymmetric dimethylarginine and C-reactive protein concentration in Bosnian patients.

Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 µmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 µmol/L; p<0.001) and in controls (0.62±0.15 µmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20-9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40-4.30) mg/L; p<0.001] and controls [0.85 (0.50-1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.

Traditional and Non-traditional Lipid Profiles in Bosnian Patients with Probable Alzheimer's Disease and Vascular Dementia.

Background: Conflicting data exist on traditional lipid profiles in patients with Alzheimer's disease (AD) and vascular dementia (VD), whereas scarce number of studies evaluated non-traditional lipid profiles in patients with AD and VD. Studies have shown that ethnic background may affect lipid profile. Objective: The aim of the present study was to conduct comparative assessment of traditional and non-traditional lipid profiles in Bosnian patients with AD and VD. Methods: A controlled, cross-sectional study was performed with 66 patients with AD, 50 patients with VD, and 60 control subjects. The Montreal Cognitive Assessment (MoCA) test was used for an evaluation of the global cognitive function. The Hachinski ischemic score was used to distinguish patients with VD from those with AD. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with ANOVA followed by the Tuckey posthoc test or with the Kruskal Wallis test followed by the Mann-Whitney test. Results: Results of the present study have shown that patients in AD group had significantly lower level of TC, TG, LDL-C, VLDL-C, Non-HDL-C and significantly lower atherogenic index compared to the control group (CG) and compared to the VD patients. Significant difference in values of TG and VLDL-C was observed between VD and the CG, whereas no significant difference in values of TC, LDL-C, atherogenic index and Non-HDL-C was observed between these two groups. Our results have also shown that TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were significantly lower in AD patients compared to the VD and CG. Moreover, TG/HDL-C ratio was significantly lower in VD compared to the CG. However, a significant difference in TC/HDL-C and LDL-C/HDL-C was not observed between VD and the CG. Conclusion: Based on the results of the present study it can be deduced that there is a difference in traditional and non-traditional lipid profiles between AD and VD patients of Bosnian descent. Obtained results suggest that lipids are decreased in AD and in VD to a certain extent. However, since there is an inconsistence in literature whether there is an association between cholesterol and cognition, large prospective studies are required to elucidate this controversy.

Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations.

BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. AIM: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. SUBJECTS AND METHODS: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. RESULTS: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine".

The "GEnomics of Musculo Skeletal Traits TranslatiOnal NEtwork": Origins, Rationale, Organization, and Prospects.

Musculoskeletal research has been enriched in the past ten years with a great wealth of new discoveries arising from genome wide association studies (GWAS). In addition to the novel factors identified by GWAS, the advent of whole-genome and whole-exome sequencing efforts in family based studies has also identified new genes and pathways. However, the function and the mechanisms by which such genes influence clinical traits remain largely unknown. There is imperative need to bring multidisciplinary expertise together that will allow translating these genomic discoveries into useful clinical applications with the potential of improving patient care. Therefore "GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork" (GEMSTONE) aims to set the ground for the: 1) functional characterization of discovered genes and pathways; 2) understanding of the correspondence between molecular and clinical assessments; and 3) implementation of novel methodological approaches. This research network is funded by The European Cooperation in Science and Technology (COST). GEMSTONE includes six working groups (WG), each with specific objectives: WG1-Study populations and expertise groups: creating, maintaining and updating an inventory of experts and resources (studies and datasets) participating in the network, helping to assemble focus groups defined by phenotype, functional and methodological expertise. WG2-Phenotyping: describe ways to decompose the phenotypes of the different functional studies into meaningful components that will aid the interpretation of identified biological pathways. WG3 Monogenic conditions - human KO models: makes an inventory of genes underlying musculoskeletal monogenic conditions that aids the assignment of genes to GWAS signals and prioritizing GWAS genes as candidates responsible for monogenic presentations, through biological plausibility. WG4 Functional investigations: creating a roadmap of genes and pathways to be prioritized for functional assessment in cell and organism models of the musculoskeletal system. WG5 Bioinformatics seeks the integration of the knowledge derived from the distinct efforts, with particular emphasis on systems biology and artificial intelligence applications. Finally, WG6 Translational outreach: makes a synopsis of the knowledge derived from the distinct efforts, allowing to prioritize factors within biological pathways, use refined disease trait definitions and/or improve study design of future investigations in a potential therapeutic context (e.g. clinical trials) for musculoskeletal diseases.

Vitamin D3 attenuates oxidative stress and regulates glucose level and leukocyte count in a semi-chronic streptozotocin-induced diabetes model.

PURPOSE: Vitamin D3 (vit-D3) is a potent immunomodulator with anti-inflammatory and antioxidative properties. We used streptozotocin (STZ)-induced rat model of diabetes (DM) to evaluate the effects of vit-D3. We measured serum biochemical parameters, interleukin-17 (IL-17), osteocalcin (OC), malondialdehyde (MDA), and immune cell count on the 21st day of experiment. METHOD: A total of 24 Wistar rats were randomly divided into three groups. Each group had eight rats. During the 1st day of the experiment, the control group was injected intraperitoneally with citrate buffer, while STZ group and STZ + vit-D3 group were injected by a single i.p. dose (35 mg/kg) of STZ dissolved in citrate buffer (pH 4,5; 0,1 M). Vitamin D3 was applied via oral gavage once daily to the STZ + vit-D3 group for a total period of 14 days, starting from the 7th day of the experiment. RESULTS: STZ rats showed a significant reduction in OC and an increase in MDA and IL-17 serum concentrations compared to the control rats. We also observed a significant STZ-associated decrease in the number of lymphocytes and a significant increase in monocyte and eosinophil number. Oral treatment with vit-D3 to STZ-induced diabetic rats significantly increased OC and decreased MDA serum levels. Furthermore, vit-D3 treatment resulted in a good regulation of hematopoiesis such as increase in the number of segmented granulocytes and lymphocytes and a reduction in the number of monocytes and eosinophils. CONCLUSION: Vit-D3 treatment has important therapeutic effects; among many others it can attenuate oxidative stress and ameliorate the hyperglycemic state in the STZ-induced rat diabetic model, which is promising for further clinical trials.

Peripheral 8-iso-PGF2α as a Biomarker in Bosnian Patients with Alzheimer's Disease and Vascular Dementia.

BACKGROUND: Cerebrospinal levels of isoprostanes (IsoPs) have been established as biomarkers of oxidative stress in Alzheimer's disease (AD) and vascular dementia (VD). The value of peripheral levels in the diagnostics of these diseases is less conclusive. The aim of this study was to determine serum 8-iso-prostaglandin-F2alpha (8-iso-PGF2α) levels in Bosnian AD and VD patients and to establish whether there is an association between 8-iso-PGF2α serum concentration and cognitive impairment (CI) in patients with dementia. SUBJECTS AND METHODS: Serum levels of 8-iso-PGF2α were measured by enzyme immunoassay method in AD (n=30) and VD patients (n=30) and control subjects (CG, n=30). The AD and VD group were further stratified according to the level of CI. RESULTS: The serum 8-iso-PGF2α levels were significantly higher in the AD (74.00 pg/mL) and VD groups (38.00 pg/mL) compared to the CG (17.50 pg/mL). A significant difference in serum 8-iso-PGF2α levels between patients with moderate and severe CI was not established in either AD or VD. CONCLUSION: Serum 8-iso-PGF2α proved to be a good biomarker in AD and VD, however it cannot be recommended for the differentiation of moderate and severe CI.

Preoperative tumour size as a predictor of the presence of lymphovascular invasion in lung adenocarcinoma.

Aim To examine whether preoperative tumour size may serve as a biomarker for the occurrence of lymphovascular invasion (LVI) in centrally and peripherally located lung adenocarcinoma. Method The study included 261 patients surgically treated for diagnosed lung adenocarcinoma. A ROC curve was used to determine the biomarker potential of tumour size relative to the occurrence of LVI. Binary logistic regression was used to show changes of tumour size impact on the status of LVI. Result Tumour prevalence according to localization had no statistical significance (p=0.464), while the presence of LVI in central, as well as peripheral positions, was statistically significantly different (p<0.001). The area under the curve of 0.978 highlights the fact that tumour size is an excellent marker of the presence of LVI in centrally located adenocarcinomas of the lung. A similar finding was confirmed in peripherally located lung adenocarcinomas with an area below the curve of 0.943. Binary logistical regression showed that in centrally localized adenocarcinomas of the lung, each additional centimetre of tumour growth represents an increase in the likelihood of LVI+ by 17.14 times. In peripherally located adenocarcinomas of the lung, this increase in likelihood of LVI for each centimetre of growth was 5.46 times. Conclusion With a high degree of sensitivity and specificity, preoperative tumour size may serve as an important biomarker and positive predictor of the presence of LVI in lung adenocarcinoma of any location.

Review of Standard Laboratory Blood Parameters in Patients with Schizophrenia and Bipolar Disorder.

INTRODUCTION: Symptomatic and etiopathologic heterogeneity of schizophrenia (SCH) and bipolar disorder (BD) can be adequately addressed using a dimensional approach to psychopathology, as well as interpreting physiological properties and markers as predictors of disease onset and relapse. Risk factors, genetic and environmental, are likely to modify the neurobiological processes characteristic of certain physiological processes that manifest to a greater degree of overlapping symptoms. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. It gives us an insight into the general somatic condition of the patient. It assesses the ability to transport oxygen to tissues and carbon dioxide back to the lungs via erythrocytes (RBC) and hemoglobin (HGB) as their most important constituents, and is also an indicator of iron status and blood oxygenation. AIM: Schizophrenia (SCH) and bipolar disorder (BD) are psychiatric disorders whose complex etiology and pathogenesis are still far from known. A correlation between red blood cell abnormalities and these diseases has been recognized in some studies. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. However, so far there is a small number of published papers that relate to the relationship between laboratory parameters of blood and the aim of this paper is to reveal more light in this subject. METHODS: The research was done as an observational prospective clinical study that has evaluated different physiological and pathological parameters in patients with BD and SCH over a two-year period. A total of 159 patients with schizophrenia, 61 patients diagnosed with bipolar disorder and 82 healthy subjects participated in this study. RESULTS: At baseline, BD compared to SCH patients had higher mean lymphocyte count (2,6±0,7 vs. 2,0±0,6x109; p=0,006) and haemoglobin concentration (146,8±12,2 vs. 140,2±14,7 g/L; p=0,03), and significantly lower red cell distribution width (13,6±2,2 vs. 14,7±1,8%; p=0,008). In both BD and SCH patients there was a significant number of patients with low red blood cells count and low haemoglobin concentration, and high MCH and MCHC at baseline and at 3 and 6 months of follow up. CONCLUSIONS: The finding that SCH as well as BD differed from controls with respect to red blood cells, hemoglobin, lymphocytes, and average platelet count was consistent with previous findings and could be understood as a qualitative measure in the evaluation of this sample. The fact that no association with other parameters was found, as well as an association with the diagnosis, does not exclude that these associations can be found in larger samples.

Bone Mineral Density Assessment by DXA vs. QCT in Postmenopausal Females with Central Obesity.

OBJECTIVES: Although Dual-energy X-ray Absorptiometry (DXA) is gold standard for osteoporosis diagnosis, several reports have shown discordant T-score values measured by Quantitative Computed Tomography (QCT) and DXA especially in obese subjects, but it is still not clear whether BMD measurement by two modalities is affected by overall obesity or central obesity in postmenopausal females. Therefore, the aims of this study were to compare BMD and T-scores by DXA and QCT and to evaluate whether these two osteoporosis assessment modalities yield different T-score values in postmenopausal females with obesity and central obesity. METHODS: This cross-sectional study enrolled 44 postmenopausal females, referred for osteoporosis screening. Anthropometric indices (BMI-body mass index, WC-waist circumference and ICOindex of central obesity) were measured and females underwent an assessment of bone mineral density by DXA and QCT. RESULTS: Lumbar Spine (LS) T-score values were observed to be significantly lower by DXA compared to qCT in females with BMI >25 kg/m2, (-1.9±1.5 vs. -2.3±1.2; p=0.039), in females with WC>88 cm(-1.9±1.5 vs. -2.4±1.2; p=0.008) and in females with ICO>0.5(-1.96±1.4 vs. -2.5±1.2; p=0.004). However, in normal-weight females and in those without central obesity, LS T-scores by DXA were not different than qCT. DXA at lumbar spine and proximal femur revealed osteoporosis in 47.7% and 11.4% respectively, while QCT detected osteoporosis in 61.4% of females (p<0.001). Measures of central obesity; ICO and WC were not associated with QCT bone mineral density (BMD) (r=0.14 and r=0.21, respectively), but were positively associated with both DXALS BMD (r=0.29 and r=0.31; p<0.05) and DXA proximal femur BMD (r=0.41 and r=0.44; p<0.01). CONCLUSION: Our results suggest that obesity is associated with lower T-scores by DXA compared to QCT. Caution is needed when assessing osteoporosis status in obese postmenopausal females. However, further studies with larger sample size are needed to confirm the findings.

Bone marrow adiposity is inversely associated with bone mineral density in postmenopausal females.

Aim To evaluate vertebral bone marrow adiposity (BMA) using magnetic resonance spectroscopy (MRS) in postmenopausal women and to determine an association of bone density with bone marrow fat content. Methods This cross-sectional study included 120 postmenopausal women referred for osteoporosis screening. All women underwent assessment of bone mineral density by dual X-ray absorptiometry (DXA), who were divided based on T scores into osteoporosis (OST; n=60) and control group (CG; n=60). MRS was used to measure fat fraction (FF), lipid/water ratio (LWR) and fat content (FC) at vertebral spine (L1-L4). Results Mean age, menopause or reproductive period duration was not significantly different between women in OST and control group. Median LWR in OST group was significantly higher compared to CG, 31.5 (22.9-38.8) vs. 28.7 (13.7-37.3) (p=0.039). Median FC was significantly higher in OST compared to the control group, 47.0 (46.3-78.8) and 46.4 (44.3-48.6), respectively (p=0.011). FC was significantly negatively associated with BMD at lumbar spine (Rho=-0.042; p<0.001) and with BMD at hip (Rho=-0.64; p<0.001). In logistic regression model, FC remained independently associated with osteoporosis after controlling for confounders (age, menopause duration, reproductive period duration and body mass index) (OR=1.3; 95% CI 1.1-1.6). Conclusion Bone marrow adiposity is an independent predictor of low bone mass in postmenopausal women suggesting its role as a therapeutic target in postmenopausal osteoporosis management.

Effects of Different Antihypertensive Drug Combinations on Blood Pressure and Arterial Stiffness.

INTRODUCTION: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). AIM: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. METHODS: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). RESULTS: SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). CONCLUSION: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.

The Triglyceride/HDL Ratio and Triglyceride Glucose Index as Predictors of Glycemic Control in Patients with Diabetes Mellitus Type 2.

INTRODUCTION: Poor glycemic control, assessed by higher glycated hemoglobin (HbA1c) levels, is associated with greater risk of diabetic complications. AIM: The aim of this study was to assess the association of triglyceride - to - HDL cholesterol (TG/HDL-C) ratio and triglyceride glucose (TyG) index with HbA1c and to evaluate their potential role as predictors of glycemic control in patients with diabetes mellitus type 2 (DM2). PATIENTS AND METHODS: This cross-sectional study was conducted in Health Center Banovici and included a total of 113 patients with DM2 classified according to their HbA1c values in two groups: DM2 HbA1c <7% - DM2 patients with good glycemic control (n=39) and DM2 HbA1c ≥7% - DM2 patients with poor glycemic control (n=74). Anthropometric, biochemical parameters and blood pressure values were measured, while TG/HDL-C ratio and TyG index were calculated. RESULTS: TG/HDL-C ratio and TyG index were significantly higher in DM2 HbA1c≥7% compared to DM2 HbA1c<7% group (p=0.003 and p<0.001; respectively). Both TG/HDL-C ratio and TyG index were positively associated with HbA1c levels (Rho=0.29; p=0.002; Rho=0.37; p<0.001; respectively). In linear regression analysis TG/HDL-C ratio and BMI, and also TyG index and BMI were significantly independently associated with HbA1c even after controlling for age, gender, diabetes duration and smoking. When we stratified patients according to BMI values, independent association between TG/HDL-C ratio and HbA1c remained significant only in normal weight subjects (OR 0.21; 95%CI: 0.05-0.37; ß=0.65; p=0.017), while independent association between TyG index and HbA1c remained significant only in overweight and obese subjects (OR 0.063; 95%CI: 0.01- 0.12; ß=0.24; p =0.027). CONCLUSION: TG/HDL-C ratio might be a useful predictor of glycemic control in normal weight, and TyG index in overweight and obese patients with DM2.

Association Between - 675 ID, 4G/5G PAI-1 Gene Polymorphism and Pregnancy Loss: A Systematic Review.

INTRODUCTION: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. AIM: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. RESULTS: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). CONCLUSIONS: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.

The value of gamma glutamyltransferase in predicting myocardial infarction in patients with acute coronary syndrome.

AIM: To assess the utility of gamma-glutamyl transferase (GGT) and C-reactive protein (CRP) in predicting troponin elevation in patients with acute coronary syndrome. PATIENTS: The total of 119 patients were divided into troponin-positive (n = 61) and troponin-negative (n = 58) patients. RESULTS: CRP cut-off value ≥13.4 mg/l had the sensitivity of 68.1% and specificity of 62.5%, while the GGT cut-off value ≥61.5 IU/l had the sensitivity of 66.0% and specificity of 62.0% and combined use of both CRP and GGT had 71.4% sensitivity and 69.6% specificity in predicting troponin increase in acute coronary syndrome patients. CONCLUSION: GGT might be used as an adjuvant marker for risk assessment patients who present with chest pain and are suspected to have acute coronary syndrome.

Serum homocysteine levels in patients with probable vascular dementia.

Aim To investigate total homocysteine (tHcy) serum concentration in patients with probable vascular dementia (VD) and in agematched controls, as well as to determine an association between tHcy serum concentration and cognitive impairment in patients with probable VD. Methods Serum concentration of tHcy was determined by the Fluorescence Polarization Immunoassay on the AxSYM System. Cognitive impairment was tested by the Mini Mental Status Examination (MMSE) score. Body mass index (BMI) was calculated for each subject included in the study. Results Age, systolic, diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 13.35 µmol/L, while in patients with probable VD it was significantly higher, 19.45 µmol/L (p=0.002). A negative but insignificant association between serum tHcy concentration and cognitive impairment in patients with probable VD was found. Conclusion Increased tHcy concentration in patients with probable VD suggests the possible independent role of Hcy in the pathogenesis of VD.

Bosnian study of APOE distribution (BOSAD): a comparison with other European populations.

BACKGROUND: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. AIM: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations. SUBJECTS AND METHODS: Overall, 170 unrelated Bosnian subjects (108 female and 62 male), aged 53.0 (±5.0) years were included in this study. Genotypes were determined by real-time PCR. RESULTS: In our group the prevalence of heterozygotes E2/E3, E2/E4 and E3/E4 was 20.6%, 3.5% and 12.9%, respectively, while the prevalence of homozygotes E2/E2, E3/E3, E4/E4 was 0.6%, 61.2% and 1.2%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 12.6%, 78.0% and 9.4%, respectively. CONCLUSIONS: In studied European populations we observed a linear, gradually increasing trend in the frequency of ε4 allele from South to North (Pearson's test 0,7656, p value <0.00001), and the Bosnian population fits into this pattern perfectly.