Matrix Metalloproteinase-2 (MMP-2) and-9 (MMP-9) Gene Variants and Microvascular Complications in Type 2 Diabetes Patients.

Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to type 2 diabetes. The MMP-2 variant -1306T showed a negative correlation with diabetic polyneuropathy (p=0.017), meaning that allele-1306T has a protective role in regards to diabetic polyneuropathy while the presence of allele -1306C increases the probability of developing diabetic polyneuropathy by 3.4 fold. Our study showed that the MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes, and for the first time an association of this gene variant and the presence of diabetic polyneuropathy was shown.

ADRB2 Gene Polymorphisms and Salbutamol Responsiveness in Serbian Children with Asthma.

Inhaled ß2 adrenergic receptor (ß2-AR) agonists are the mainstay of asthma therapy. The ß2-AR protein is encoded by the ADRB2 gene and variants within this gene can have significant consequences for modulating the response to asthma therapy. This cross-sectional study performed at the University Children's Hospital in Belgrade, included 54 children with asthma. The subjects were genotyped for ADRB2 +46A>G (Arg16Gly, rs1042713) and +79C>G (Gln27Glu, rs 1042714) polymorphisms and the association with asthma severity and response to inhaled salbutamol was examined. In Serbian asthmatic children, allele +46A was detected with a frequency of 41.7% and allele +79G was detected with a frequency of 23.1%. Allele +46G was found to be associated with a better response to inhaled salbutamol (p <0.05) and with mild form of asthma (p <0.05). Polymorphism ADRB2 +46A>G may be a determinant of asthma severity and response to salbutamol in children with asthma. We did not find any association of +79C>G polymorphisms with the asthma severity and bronchodilator response to inhaled salbutamol. The results of this study can be potentially useful for personalization of asthma treatment.

Prospective measurement of quality of life in myotonic dystrophy type 1.

INTRODUCTION: Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 (DM1). AIM: To analyze changes of Individualized Neuromuscular Quality of Life questionnaire (INQoL) scores in clinic patients with DM1 over a 6-year period. METHOD: Patients completed the INQoL at baseline and after a 6-year period through their attendance in a neurology outpatient clinic. Severity of muscular involvement in DM1 was analyzed using the Muscular Impairment Rating Scale (MIRS). RESULTS: Ninety-nine DM1 patients completed a baseline visit. Sixty-seven of these patients were retested at an interval time. The overall INQoL score improved in our sample of patients (P<.05) as did the following subscales: myotonia (P<.05), pain (P<.05), activities (P<.01), social relationships (P<.01), and body image (P<.05). No changes were observed for the independence and emotions scales. There were no differences in mean change of INQoL scores between patients with worsened MIRS and those with no change in MIRS scale after follow-up (P>.05). CONCLUSION: Individualized Neuromuscular Quality of Life questionnaire scores improved in our cohort of DM1 patients during a 6-year period. INQoL score did not correlate with progression of muscle weakness. This must be better understood before the selection of the instrument for use in trials to measure therapeutic benefit in DM1 patients.

Electrophysiological findings in patients with low density lipoprotein receptor related protein 4 positive myasthenia gravis.

BACKGROUND AND PURPOSE: The aim was to determine the electrophysiological profile of our cohort of low density lipoprotein receptor related protein 4 (LRP4) positive myasthenia gravis (MG) patients. METHODS: A repetitive nerve stimulation (RNS) test and jitter analysis using a concentric needle electrode were performed in 17 LRP4 positive MG patients. The results were compared to 31 muscle-specific tyrosine kinase (MuSK) positive and 28 acetylcholine receptor (AChR) positive MG patients. RESULTS: The RNS test was negative in almost all patients belonging to the LRP4/seronegative and LRP4/MuSK groups. It was positive most frequently in the AChR MG patients, especially those without anti-LRP4 antibodies. The presence of anti-LRP4 antibodies was connected to lower decrement values, whilst the independent presence of anti-AChR or anti-MuSK antibodies was connected to higher decrement values. Lowest jitter was recorded in patients with LRP4/seronegative MG. The highest percentage of pathological jitter analysis test results was present in MuSK and AChR MG patients. The isolate presence of anti-LRP4 antibodies did not influence the mean consecutive difference values, whilst mean consecutive difference values were higher in the presence of anti-AChR or anti-MuSK antibodies. CONCLUSIONS: Low density lipoprotein receptor related protein 4 positive patients make a distinct MG subgroup with rarely detected pathological electrophysiological test results. The lack of influence of anti-LRP4 antibodies on the different electrophysiological parameters brings into question the pathogenic role of anti-LRP4 antibodies in MG.

Morphologic predictors of in hospital mortality in acute type III aortic dissection. / Morfologicheskie prediktory gospital'noi smertnosti u bol'nykh s ostrym rassloeniem aorty III tipa.

INTRODUCTION: In-hospital mortality of acute aortic type III dissection ranged about 12%. Complicated dissections represent about 18% of all cases, and require open surgery or TEVAR. More morphological predictors of in hospital mortality are needed to differentiate patients who should be selected for immediate, surgical or endovascular intervention. METHODS: From January 2009 to December 2014, 74 patients with acute aortic type III dissection were enrolled at Clinic of Vascular and Endovascular Surgery in Belgrade Serbia and retrospectively analyzed. Every MSCT was observed in regard to morphologic characteristics of dissection. RESULTS: By analyzing morphologic parameters in patients between survival and non-survival group only localization of intimal tear showed statistical significance (p=0,020). The size of the intimal tear didn't reach statistical significance with the tendency of doing so in a larger sample of patients (p=0,063) with the cut-off value of 9.55mm. The shape of the true lumen was on the border of statistical significance (p=0,053). CONCLUSION: Inner curvature intimal tear localization, huge intimal tear as well as elliptic shape of the true lumen together should raise awareness to a subgroup at risk for in hospital mortality. More liberal endovascular treatment in this subgroup of patients is advocated.

High frequency of DQB1*05 and absolute absence of DRB1*13 in muscle-specific tyrosine kinase positive myasthenia gravis.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of allelic variants, the aim of this study was to explore the human leukocyte antigen (HLA) profile of our patients with muscle-specific tyrosine kinase (MuSK) MG. METHODS: Human leukocyte antigen (HLA) typing was performed in our cohort of 31 MuSK MG patients available for the study. The allele groups of DRB1* and DQB1* loci were typed with sequence-specific oligonucleotide probes and high resolution typing for DQB1* was performed using sequence-specific primers. HLA frequencies were compared with unrelated healthy bone marrow donors. RESULTS: Significant association of MuSK MG with alleles DRB1*14 [odds ratio (OR) 3.8], DRB1*16 (OR 3.3) (P < 0.01) and DQB1*05 (OR 2.2) (P < 0.05) was found. In our patients the most frequent DQB1* allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of MuSK MG patients was also found, whilst this allele was present in 25% (495/1992) of control subjects (OR 0) (P < 0.01). The HLA DRB1*16-DQB1*05 (OR 2.9) haplotype was found to be associated with MuSK MG (P < 0.05). CONCLUSIONS: The strong association of MuSK MG with DQB1*05 alleles observed in patient series from other countries was confirmed. The novel finding in our cohort of MuSK MG patients was the absolute absence of DRB1*13 allele, which might have a protective role in the development of MuSK MG, at least in our population.

The impact of ultrasound-guided erector spinae plane block on hemodynamic stability and postoperative pain in patients undergoing modified radical mastectomy for breast cancer.

OBJECTIVE: Breast cancer, a prevalent global malignancy in women, necessitates a comprehensive treatment approach, with surgery playing a crucial role. Severe acute pain is common post-radical breast cancer surgery, emphasizing the significance of hemodynamic stability and postoperative pain control for optimal outcomes. This study evaluates the impact of ultrasound-guided erector spinae plane block (ESPB) on these parameters in ASA scores 1-2 patients undergoing modified radical breast cancer surgery with general anesthesia. PATIENTS AND METHODS: Forty-eight patients were divided into two groups: a general anesthesia group, with erector spinae plane block (GA+ESPB), and a control group receiving only general anesthesia (GA). Hemodynamic parameters were continuously monitored, and postoperative pain was assessed using the visual analog scale (VAS) at various time points. RESULTS: Ultrasound-guided ESPB effectively maintained hemodynamic stability and reduced postoperative pain in breast cancer surgery patients. Statistically significant differences were observed in heart rate, systolic and diastolic blood pressure, and mean arterial pressure between the GA and GA+ESPB groups at multiple time points (p < 0.05). VAS scores showed a significant interaction time*group (p < 0.001), with consistent differences between the groups at all time points (p ≤ 0.001). CONCLUSIONS: Ultrasound-guided ESPB application proved effective in preserving hemodynamic stability and managing postoperative pain in modified radical breast cancer surgery. The technique demonstrates promise in minimizing complications related to hemodynamic variations and postoperative pain, contributing to a comprehensive approach to breast cancer surgical treatment.

Epidemiological study of adult-onset myasthenia gravis in the area of Belgrade (Serbia) in the period 1979-2008.

BACKGROUND: The aim of this study was to analyze the prevalence and incidence of adult-onset myasthenia gravis (MG) in the Belgrade population from 1979 to 2008. METHODS: Data on the number of MG patients and their basic demographic and clinical characteristics were collected from hospital records (1979-1992) and the Belgrade MG Registry (1993-2008). Incidence and prevalence were standardized by the direct method (using the world standard population). A time-trend analysis of MG incidence was performed using a linear regression model. RESULTS: During the study period 562 cases (316 women, 246 men) were registered. On December 31st, 2008, the standardized prevalence (according to the world standard population) was 188.3/1,000,000 (women: 237.8/1,000,000; men: 139.4/1,000,000). The average annual standardized incidence rate was 13.3/1,000,000 (women: 14.1/1,000,000; men: 12.2/1,000,000). The incidence rates tended to increase significantly in both sexes during the study period (y = 3.299 + 14.363x, p = 0.002). Age-specific incidence rates for women demonstrated a bimodal pattern, with the first peak in the 20- to 29-year age group and the second one in the ≥70-year group. For both genders, an increase in age-specific incidence rates was registered for all age groups, although this was significant (p = 0.001) only for an MG onset of ≥60 years of age. CONCLUSIONS: The study confirms an increase in the incidence of MG in the area of Belgrade during the study period, especially for those with MG onset after 60 years of age.

Comparative structural and optical properties of different ceria nanoparticles.

Herein a comparative study of five nanocrystalline cerium oxides (CeO(2-delta)) synthesised by different methods and calcined at 500 degrees C is reported. XRPD analysis showed that stoichiometry parameter delta, crystallite size/strain and lattice constant were only slightly affected by the method utilized. All ceria nanoparticles are nearly spherical in shape with faceted morphology, free of defects and with a relatively uniform size distribution. The average microstrain was found to be approximately 10 times higher than that of bulk counterpart. The absorption edge of nanocrystalline materials was shifted towards a higher wavelengths (red shift) in comparison with bulk counterpart, and band gap values were in the range 2.7-3.24 eV (3.33 eV for bulk counterpart).

Ultrasound assessment of cervical status compared to the Bishop score - predicting the success of labor induction using a machine learning-based model.

OBJECTIVE: The main aim of this study was to develop a machine-learning-based model for predicting the success of labor induction (IOL). To that end, the clinical and ultrasound parameters that affect the successfulness of labor induction were assessed. Then, a new ultrasound scoring system (USS) was developed and assessed. PATIENTS AND METHODS: This prospective observational study included 192 term women who underwent induction of labor. First, a wide range of clinical and ultrasound pre-induction parameters were recorded. The induction was initiated by endocervical administration of dinoprostone gel (for Bishop score ≤5) or intravenous oxytocin (for Bishop score ≥6). After evaluating ultrasound parameters, we created an ultrasound scoring system and compared it with the Bishop score and clinical parameters. Finally, a comprehensive model using machine learning algorithms for predicting the success of the induction of labor was developed. RESULTS: In terms of clinical parameters, this study found that IOL correlates with parity, body mass index (BMI) (both at p<0.05), and the Bishop score (p<0.001). All ultrasound parameters were statistically significant (p<0.05) apart from the posterior cervical angle. However, compared to the Bishop score, the new USS showed a slightly lower sensitivity (0.55 compared to 0.64) but much higher specificity (0.75 compared to 0.44) at a cut-off of 1.66. The proposed model, which can predict 83% of the events correctly, encompasses the Bishop score, USS, and clinical parameters. CONCLUSIONS: The findings imply that the model developed in this study, which takes into account clinical parameters (parity, BMI), the ultrasound parameters and the Bishop score and uses machine learning algorithms, yields better results than models using other parameters.

Effects of Eu3+ concentration on structural, optical and vibrational properties of multifunctional Ce(1-x)Eu(x)O2-delta) nanoparticles synthesized by thermolysis of 2,4-pentanedione complexes.

The 5-10 nm Ce(1-x)Eu(x)O(2-delta) (0 < or = x < or = 0.30) nanoparticles with fluorite structure were synthesized by thermal decomposition of Eu- and Ce-2,4-pentanedione complexes mixtures. X-ray line broadening analysis of mixed samples Ce(1-x)Eu(x)O(2-delta) (0.05 < or = x < or = 0.30) showed that the crystallite size was lower and root mean square strain higher than in pure ceria. However, within mixed samples Ce(1-x)Eu(x)O(2-delta) (0.05 < or = x < or = 0.30) crystallite size and root mean square strain were independent of Eu3+ concentration. Raman spectroscopy results indicated that europium ions yield disorder by breaking the phonon propagation and therefore making the non-centre Brillouin zone modes Raman active. The absorption bands in the spectra of mixed oxides were blue-shifted in comparison to pure CeO(2-delta) nanopowder. The samples show red emission typical for Eu ions. The biggest photoluminescent intensity was observed for the highest Eu3+ concentration (x = 0.30) and further enhanced with the increase in crystallinity.

Human giardiasis in Serbia: asymptomatic vs symptomatic infection.

Despite the public health importance of giardiasis in all of Europe, reliable data on the incidence and prevalence in Western Balkan Countries (Serbia, Bosnia and Herzegovina, Croatia, Montenegro and FYR Macedonia) are scarce, and the relative contribution of waterborne and food-borne, or person-to-person and/or animal-to-person, transmission of human giardiasis is not yet clear. To provide baseline data for the estimation of the public health risk caused by Giardia, we here review the information available on the epidemiological characteristics of asymptomatic and symptomatic human infection in Serbia. Although asymptomatic cases of Giardia represent a major proportion of the total cases of infection, high rates of Giardia infection were found in both asymptomatic and symptomatic populations. No waterborne outbreaks of giardiasis have been reported, and it thus seems that giardiasis mostly occurs sporadically in our milieu. Under such circumstances, control measures to reduce the high prevalence of giardiasis in Serbia have focused on person-to-person transmission, encouraging proper hygiene, but for more targeted intervention measures, studies to identify other risk factors for asymptomatic and symptomatic infections are needed.

Optimization of photoluminescence of Y(2)O(3):Eu and Gd(2)O(3):Eu phosphors synthesized by thermolysis of 2,4-pentanedione complexes.

Spherical shaped nanoparticles of series Y(2 - x)Eu(x)O(3) (x = 0.06, 0.10, 0.20, and 2) and Gd(2 - x)Eu(x)O(3) (x = 0.06, 0.10) were prepared by thermolysis of 2,4-pentanedione complexes of Y, Gd, and Eu. The bixbyite phase of Gd(2 - x)Eu(x)O(3) samples was formed at 500 degrees C, whereas the thermal decomposition of Y and Eu complexes' mixtures occurred at higher temperatures. Linearity in the concentration dependence on lattice parameter confirmed the formation of solid solutions. The distribution of Eu(3+) in Gd(2 - x)Eu(x)O(3) was changed with thermal annealing: in the as-prepared sample (x = 0.10) the distribution was preferential at C(3i) sites while in the annealed samples, Eu(3+) were distributed at both C(2) and C(3i) sites. Rietveld refinement of site occupancies as well as emission spectra showed a random distribution of cations in Y(2 - x)Eu(x)O(3). The photoluminescence (PL) measurements of the sample showed red emission with the main peak at 614 nm ((5)D(0)-(7)F(2)). The PL intensity increased with increasing concentration of Eu(3+) in both series. Infrared excitation was required to obtain good Raman spectra. The linear dependence of the main Raman peak wavenumber offers a non-destructive method for monitoring the substitution level and its homogeneity at the micron scale.

Validation of Serbian version of the disease-specific myasthenia gravis questionnaire.

AIM: The aim of this study was to validate translated and cross-cultural adapted Italian version of myasthenia gravis-specific questionnaire (MGQ) in Serbian MG patients. MATERIALS AND METHODS: The questionnaire was validated in 140 consecutive MG patients from Belgrade. In each patient association between the total MGQ score and form and severity of the disease was determined. Also, correlation between regional domain scores of MGQ and main clinical findings according to Besinger's clinical score was analyzed. RESULTS: Patients' participation in the assessment was satisfactory with excellent internal consistency and reproducibility. Total MGQ score, as well as domain scores, correlated with highly significant inverse relationship with the disease severity and clinical status of patients at the moment of completing the questionnaire. Furthermore, the bulbar domain of the questionnaire appeared more specific and sensitive than clinical history and examination. CONCLUSION: We concluded that the Serbian version of the MGQ may be useful as a measure of clinical outcome in patients with MG.

The structure of sterile cytoplasm types within a maize genebank collection.

Maize Research Institute (MRI) gene bank maintains a collection of 6000 maize accessions. Within this collection over 100 sources of cytoplasmic male sterility (CMS) were found in field trials, i.e. more than 2% of the total accession numbers. These sources are distributed among Yugoslav open-pollinated varieties (4.56% of them contain CMS), as well as introduced heterozygous genotypes and inbred lines. In order to identify cytoplasm types the gene-bank sources of CMS were screened using a PCR assay with specific primers for C, T and S cytoplasms. Predominant cytoplasmic male sterility type among the analyzed accessions was CMS-S. Results were inconclusive for three accessions, i.e. different results for the progenies of two ears per accession were obtained. For another two accessions a new PCR product profile was identified, consisting of one band characteristic for CMS-S and one unspecific for any of the three CMS types. The PCR approach enabled a simple, fast and reliable large scale screening of maize cytoplasm among MRI gene bank accessions, significantly reducing time for cytoplasm characterizations compared to classical method of testing with restorers for each known type of CMS.

Ssr analysis for genetic structure and diversity determination of maize local populations from former Yugoslavia territories.

A collection of 2178 local populations from ex-Yugoslavia territories is maintained in Maize Research Institute (MRI) gene bank. These populations were characterized mainly by morphological markers. In this work 21 local populations belonging to seven different agro-ecological groups have been subjected to SSR analysis using a DNA-pooling strategy. The objective of this work was to develop genetic fingerprints for characterization, identification and classification of the populations, as well as for estimation of their genetic diversity. Also, a DNA-pooling strategy was employed with the aim to certify if it could be applied for population analysis with SSR markers. Statistical analysis of 25 informative SSR primers revealing 224 alleles (bands) showed that the average within-population mean number of alleles was 2.55, the average values for total and within-population diversity were 0.784 and 0.502, respectively and G(ST) value was 0.360. Genetic distance values calculated using Modified Rogers' Distance were in the range from 0.35 to 0.60. The silver staining method of DNA used for bulked samples showed some weakness that could be overcome with a more sensitive staining method. Nevertheless, the results in this work indicate that the SSR analysis of bulks could be used for characterizing a large number of populations in gene banks.

Corticosteroids in chronic inflammatory demyelinating polyneuropathy : A retrospective, multicentre study, comparing efficacy and safety of daily prednisolone, pulsed dexamethasone, and pulsed intravenous methylprednisolone.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) can be treated with corticosteroids or intravenous immunoglobulins. Various corticosteroid regimens are currently used in CIDP, but it is unknown whether they are equally efficacious. In this retrospective study, we compared efficacy and safety of three corticosteroid regimens in CIDP patients. METHODS: We included treatment naïve patients that fulfilled the EFNS/PNS criteria for CIDP. Patients were treated with corticosteroids according to the local protocol of three CIDP expertise centres. Corticosteroid regimens consisted of daily oral prednisolone, pulsed oral dexamethasone, or pulsed intravenous methylprednisolone. Outcomes were number of responders to treatment, remission rate of treatment responders, overall probability of 5-year remission, and the occurrence of adverse events. RESULTS: A total of 125 patients were included. Sixty-seven (54%) patients received daily prednisone or prednisolone, 37 (30%) pulsed dexamethasone, and 21 (17%) pulsed intravenous methylprednisolone. Overall, 60% (95% CI 51-69%) responded to corticosteroids, with no significant difference between the three treatment regimens (p = 0.56). From the 75 responders, 61% (95% CI 50-73%) remained in remission, during a median follow-up of 55 months (range 1-197 months). The probability of responders reaching 5-year remission was 55% (95% Cl 44-70%), with no difference between the three groups. Adverse events leading to a change in treatment occurred in ten patients (8%). Two patients had a serious adverse event. CONCLUSION: Corticosteroids lead to improvement in 60% of patients and to remission in 61% of treatment responders. There were no differences between treatment modalities in terms of efficacy and safety.

Undercooked meat consumption remains the major risk factor for Toxoplasma infection in Serbia.

Toxoplasma gondii infection prevalence and infection risk factors were analyzed in a series of 765 women of generative age from throughout Serbia tested at the Institute for Medical Research Toxoplasmosis Laboratory between 2001 and 2005. The infection risk factors were additionally analyzed in a group of 53 women with acute infection (cases) compared to a group of seronegative women matched for age and education level (controls). The overall prevalence of infection was 33%. Infection risk factors in the whole series were undercooked meat consumption (RR = 1.77, 95% CI = 1.16-2.7, P = 0.008) and exposure to soil (RR = 1.63, 95% CI = 1.17-2.29, P = 0.004), particularly in less educated women. Moreover, undercooked meat consumption was the single predictor of infection in women with acute infection, with an 11-fold increased risk of infection in women who acknowledged consumption of undercooked meat (RR = 11.21, 95% CI = 3.10-40.53, P = 0.000). These data prompted us to analyze the significance of consumption of particular meat types as sources of infection. Of all the meat types mostly consumed in Serbia, only consumption of beef (RR = 1.006, 95% CI = 1.001-1.011, P = 0.027) was shown to influence Toxoplasma infection rates.