Publications by authors named "Nataša Nikolić"

43 Publications

The prevalence of 30 HPV genotypes detected by EUROArray HPV in cervical samples among unvaccinated women from Vojvodina province, Serbia.

PLoS One 2021 14;16(4):e0249134. Epub 2021 Apr 14.

Merck Sharp & Dohme D.O.O., Belgrade, Serbia.

This study evaluates the pre-vaccination prevalence of HPV infection in women from Vojvodina, Serbia, according to age and cytological status. A total of 1,495 women, ranging from 18 to 65 years of age, with different cytological results were enrolled. The HPV genotyping assay was performed using the EUROArray HPV test in order to detect thirty genitally relevant HPV subtypes. In our study, the most prevalent genotypeswere HPV 16, 31, 51, and 53. Among these, HPV 16 was consistently present in all cytological subgroups. Twelve HPV genotypes classified as carcinogenic to humans (Group 1) were detected in 77.8.0% of HSIL/ASCH and 55.0% of NILM with abnormal colposcopy findings. Six possible carcinogens-HRs (group 2B) were often found in women with normal cytology (14.8%) and mild abnormalities (ASCUS and LSIL), but with lower frequence in HSIL/ASCH lesions (7.1%). HPVs 6 and 11(Group 3) were not found in the cases of HSIL/ASCH. Unclassified HPV types were equally distributed in all cytology groups: 20.7%, 19.1%, 16.3% and 13% of NILM, ASCUS, LSIL and HSIL/ASCH, respectively. Our findings highlight that majority of abnormal Pap test results are caused by Group 1 HPVs among women from our region. Low frequency HPVs of group 2A/2B, especially HSIL/ASCH, supports the conclusion that individual genotypes require consideration of each type as an individual agent. We expect a positive impact of HPV vaccine in reducing HPV-associated cervical lesions among women from Vojvodina province, after establishing vaccination programs in our country.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249134PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046239PMC
April 2021

Effect of differentiation, de novo innervation, and electrical pulse stimulation on mRNA and protein expression of Na+,K+-ATPase, FXYD1, and FXYD5 in cultured human skeletal muscle cells.

PLoS One 2021 26;16(2):e0247377. Epub 2021 Feb 26.

Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Denervation reduces the abundance of Na+,K+-ATPase (NKA) in skeletal muscle, while reinnervation increases it. Primary human skeletal muscle cells, the most widely used model to study human skeletal muscle in vitro, are usually cultured as myoblasts or myotubes without neurons and typically do not contract spontaneously, which might affect their ability to express and regulate NKA. We determined how differentiation, de novo innervation, and electrical pulse stimulation affect expression of NKA (α and β) subunits and NKA regulators FXYD1 (phospholemman) and FXYD5 (dysadherin). Differentiation of myoblasts into myotubes under low serum conditions increased expression of myogenic markers CD56 (NCAM1), desmin, myosin heavy chains, dihydropyridine receptor subunit α1S, and SERCA2 as well as NKAα2 and FXYD1, while it decreased expression of FXYD5 mRNA. Myotubes, which were innervated de novo by motor neurons in co-culture with the embryonic rat spinal cord explants, started to contract spontaneously within 7-10 days. A short-term co-culture (10-11 days) promoted mRNA expression of myokines, such as IL-6, IL-7, IL-8, and IL-15, but did not affect mRNA expression of NKA, FXYDs, or myokines, such as musclin, cathepsin B, meteorin-like protein, or SPARC. A long-term co-culture (21 days) increased the protein abundance of NKAα1, NKAα2, FXYD1, and phospho-FXYD1Ser68 without attendant changes in mRNA levels. Suppression of neuromuscular transmission with α-bungarotoxin or tubocurarine for 24 h did not alter NKA or FXYD mRNA expression. Electrical pulse stimulation (48 h) of non-innervated myotubes promoted mRNA expression of NKAβ2, NKAβ3, FXYD1, and FXYD5. In conclusion, low serum concentration promotes NKAα2 and FXYD1 expression, while de novo innervation is not essential for upregulation of NKAα2 and FXYD1 mRNA in cultured myotubes. Finally, although innervation and EPS both stimulate contractions of myotubes, they exert distinct effects on the expression of NKA and FXYDs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247377PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909653PMC
February 2021

Validation of the STANDARD Q COVID-19 antigen test in Vojvodina, Serbia.

PLoS One 2021 22;16(2):e0247606. Epub 2021 Feb 22.

Department of Epidemiology, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia.

Background: Since COVID-19 pandemic is a global crisis, tests with high sensitivity and specificity are crucial for the identification and management of COVID-19 patients. There is an urgent need for low-cost rapid antigen COVID-19 test with a good diagnostic performance. Although various antigen rapid detection tests are widely available, strong evidence of their usefulness in clinical practice are still limited. Therefore, our aim was to evaluate clinical performance of STANDARD Q COVID-19 Ag Test (SD Biosensor, Gyeonggi-do, South Korea).

Methods: The performance of the STANDARD Q COVID-19 Ag Test for the detection of SARS-CoV-2 antigen was evaluated in comparison to RT-qPCR results in 120 symptomatic patients (median age 49, IQR 36-70) who presented to health care facility in Novi Sad, Vojvodina, Serbia.

Results: Twenty five out of 120 samples have been tested positive using STANDARD Q COVID-19 Ag Test, and all of them were also positive on RT-qPCR. Overall, the STANDARD Q COVID-19 Ag Test showed sensitivity of 58.1% (95% CI 42.1-73.0) but it was higher in the early days of disease, when the highest viral loads were detected. During the first five days after the symptom onset, the sensitivity ranged from 66.7% to 100% and the pooled accuracy and Kappa values were high (0.92 and 0.852).

Conclusions: A strong agreement between performance of STANDARD Q COVID-19 Ag Test and RT-qPCR was observed during the first five days of illness, suggesting that this rapid antigenic test can be very useful for COVID-19 diagnosis in the early phase of disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247606PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899368PMC
March 2021

Health assessment of medicinal herbs, celery and parsley related to cadmium soil pollution-potentially toxic elements (PTEs) accumulation, tolerance capacity and antioxidative response.

Environ Geochem Health 2021 Jan 13. Epub 2021 Jan 13.

Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad, Serbia.

Celery and parsley are recognized as medicinal herbs and nutraceutical vegetables due to their valuable pharmacological properties and numerous health benefits. However, in recent years, soil loadings with various PTEs have become a serious concern across the world, leading to plants pollution, which can consequently diminish their quality and safety for human consumption. Therefore, we attempted to quantify quality and safety of celery and parsley grown in Cd polluted soil. We examined the presence of PTEs: As, Cu, Fe, Mn, Ni, Cu and Cd in soil and selected herbs, as well as their physiological responses to different Cd exposures (control-without Cd addition, 3 and 6 µg/g Cd of dry soil). Following elevation of Cd in plants, both species showed increasing trend of As, Pb and Cu in plants, which overcome safe limits, with exception for Cu. Further, celery showed strong phytoextraction ability (99.9 µg/g Cd of dry weight) with high potential to tolerate Cd due to the efficient antioxidative machinery. Besides that herbs pollution was evident on the basis of target hazard quotients (HQ), hazard index (HI) and cancerogenic risk (CR), revealing that chronic consumption of contaminated herbs can consequently endanger human health. HI was greater than 1, while CR exceeded safe limits in treated plants, with exception for As. In the point of view of toxicology and food safety, growing of medicinal plants should be strictly regulated and distinguished based on the purpose of growing, and further herbs usage.
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http://dx.doi.org/10.1007/s10653-020-00805-xDOI Listing
January 2021

Innervation and electrical pulse stimulation - in vitro effects on human skeletal muscle cells.

Appl Physiol Nutr Metab 2021 Apr 6;46(4):299-308. Epub 2020 Aug 6.

Department of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Norway.

Contraction-induced adaptations in skeletal muscles are well characterized in vivo, but the underlying cellular mechanisms are still not completely understood. Cultured human myotubes represent an essential model system for human skeletal muscle that can be modulated ex vivo, but they are quiescent and do not contract unless being stimulated. Stimulation can be achieved by innervation of human myotubes in vitro by co-culturing with embryonic rat spinal cord, or by replacing motor neuron activation by electrical pulse stimulation (EPS). Effects of these two in vitro approaches, innervation and EPS, were characterized with respects to the expression of myosin heavy chains (MyHCs) and metabolism of glucose and oleic acid in cultured human myotubes. Adherent human myotubes were either innervated with rat spinal cord segments or exposed to EPS. The expression pattern of MyHCs was assessed by quantitative polymerase chain reaction, immunoblotting, and immunofluorescence, while the metabolism of glucose and oleic acid were studied using radiolabelled substrates. Innervation and EPS promoted differentiation towards different fiber types in human myotubes. Expression of the slow MyHC-1 isoform was reduced in innervated myotubes, whereas it remained unaltered in EPS-treated cells. Expression of both fast isoforms (MyHC-2A and MyHC-2X) tended to decrease in EPS-treated cells. Both approaches induced a more oxidative phenotype, reflected in increased CO production from both glucose and oleic acid. Innervation and EPS favour differentiation into different fiber types in human myotubes. Both innervation and EPS promote a metabolically more oxidative phenotype in human myotubes.
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http://dx.doi.org/10.1139/apnm-2019-0575DOI Listing
April 2021

ribotype distribution in a large teaching hospital in Serbia.

Gut Pathog 2020 22;12:26. Epub 2020 May 22.

1University of Belgrade, Faculty of Medicine, Dr Subotića 8, 11000 Belgrade, Serbia.

Background: The global epidemic of nosocomial diarrhea caused by ( started in 2000, with high mortality rates and emergence of a new hypervirulent strain NAP1/BI/027. The aim of this study was to assess the presence of ribotype 027 and other ribotypes in a Serbian University Hospital, compare the temporal variability of ribotypes 3 years apart, as well as to compare clinical, demographic and laboratory characteristics and disease outcome among patients infected with 027 and non-027 ribotype. This was a prospective observational cohort study addressing 4-month intervals during 2014/2015 and 2017/2018.

Results: Ribotyping was performed in 64 non-duplicate strains. Ribotype 027 was the most prevalent, and was detected in 53 (82.8%) patients (43/45 and 10/19 patients in 2014-2015 and 2017/2018, respectively). Other detected ribotypes were 001/072 in 4 (6.3%), 002 in 4 (6.3%), 014/020 in 2 (3.1%) and 176 in 1 (1.5%) patient. The percentage of the patients infected with ribotype 027 significantly decreased during the 3-year period, from 95.6 to 52.6% (< 0.001). Ribotype 027 infection was associated with fluoroquinolone treatment more frequently than infection with other ribotypes [33 (62.3%) vs. 2 (18.2%), = 0.010)]. A severe infection was diagnosed more often in patients with the detected ribotype 027 compared to those infected with non-027 ribotypes (p = 0.006). No significant difference in the mortality and recurrence rates was found between the patients infected with ribotype 027 and those infected with other ribotypes [10/53 (18.8%) vs. 2/11 (18.2%), p = 0.708, and 10/35 (28.6%) vs. 0/2 (0%), p = 1.000, respectively].

Conclusion: ribotype 027 was the most prevalent ribotype among patients in a large Serbian hospital, but there is a clear decreasing trend.
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http://dx.doi.org/10.1186/s13099-020-00364-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243319PMC
May 2020

Genetic variability of the neuraminidase gene of influenza A(H1N1)pdm09 viruses circulating from the 2012/2013 to 2017/2018 season in Vojvodina Province, Serbia.

Mol Cell Probes 2020 08 5;52:101557. Epub 2020 Mar 5.

Institute of Public Health of Vojvodina, Futoska 121, 21000, Novi Sad, Serbia; University of Novi Sad, Medical Faculty, Hajduk Veljkova 1-3, 21000, Novi Sad, Serbia.

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http://dx.doi.org/10.1016/j.mcp.2020.101557DOI Listing
August 2020

Risk factors associated with poor clinical outcome in pyogenic spinal infections: 5-years' intensive care experience.

J Infect Dev Ctries 2020 01 31;14(1):36-41. Epub 2020 Jan 31.

Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia.

Introduction: Management of pyogenic spinal infections (PSI) after the development of neurological deficit has not been specifically addressed in the literature. We aimed to describe real-life clinical outcomes of PSI in patients admitted to an intensive care unit with neurological deficit and identify factors associated with good prognosis.

Methodology: Consecutive patients admitted to ICU with a possible diagnosis of spinal infection over five years' period were included. Descriptive statistics were performed to examine the demographics and clinical parameters.

Results: The majority (71%) of patients were male. The mean age was 57.4 years (27-79), and 71% were > 50 years old. At least one underlying risk factor was identified in 68% of the patients; the most common comorbidity was diabetes mellitus (DM). All patients have presented with fever accompanied by a neurological deficit (86%) and back pain (79%). A complete recovery was achieved in 25% of patients. However, the majority of patients had adverse outcomes with 21.4% mortality, and 43% remaining neurological sequelae. Increased age with a cut-off of 65 years and pre-existing DM were identified as being associated with poor outcome.

Conclusion: Mortality among patients admitted to ICU with PSI was significantly higher than reported in the literature. The residual neurological deficit was common, one-third of patients had remaining neurological sequelae, and only one-fourth had complete recovery. Increased age and background DM were the most important determinants of poor clinical outcome. The impact of DM appears to be much more important than currently recognised in this population.
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http://dx.doi.org/10.3855/jidc.12260DOI Listing
January 2020

IL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury.

J Infect Dev Ctries 2019 05 31;13(6):526-535. Epub 2019 May 31.

Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia.

Introduction: Patients with severe fibrosis or cirrhosis are at high risk for liver-related complications, even after successful antiviral treatment and/or regression of fibrosis. These are the first published results concerning the role of IL-28B genotypes as predictors of the durability of sustained virological response (SVR) and long-term outcome, in patients with baseline severe fibrosis and cirrhosis caused by hepatitis C (HCV) infection.

Methodology: Genetic testing for three different single nucleotide polymorphisms (SNP) near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed in 42 patients with HCV-related advanced fibrosis and cirrhosis, who achieved SVR after successful interferon-based treatment. Baseline clinical and laboratory parameters were analysed, as well as IL28B genotype association with late virological relapse, fibrosis progression and clinical outcomes.

Results: The most prevalent genotypes in all three tested SNP positions were: CCrs12979860 genotype in 69% of patients, GTrs8099917 in 78.6% and GGrs12980275 in 47.6% of patients. The presence of IL28B CCrs12979860 genotype was identified as a negative predictor of late virological relapse. Further analysis did not confirm the association of other IL28B genotypes with the progression of fibrosis and clinical outcomes.

Conclusions: Varying long-term prognosis in patients with HCV-related severe fibrosis and cirrhosis is due to multiple interactions between host genetic factors, virus and environment. These are first published results demonstrating the significance of IL28B CCrs12979860 genotype as a negative predictor of late virological relapse. A further investigation concerning genetic factors is necessary to identify patients under risk for late relapse, complications and unfavorable outcomes, so that they can be reevaluated and offered new treatment options.
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http://dx.doi.org/10.3855/jidc.11351DOI Listing
May 2019

Citric acid as soil amendment in cadmium removal by L., alterations on biometric attributes and photosynthesis.

Int J Phytoremediation 2020 31;22(1):29-39. Epub 2019 Jul 31.

Faculty of Sciences, Department of Biology and Ecology, University of Novi Sad, Novi Sad, Serbia.

During the past decade, the target in cleaning polluted sites is an application of chelating agents, such as citric acid (CA), which is proposed as a good candidate in the promotion of phytoremediation. Among heavy metals, cadmium (Cd) is one of the most common and dangerous elements, which strongly disturbs morphophysiological properties in plants. A pot experiment was assessed to evaluate the influence of CA in Cd phytoremediation in alkaline soil by (clone SV068). The effects of CA on Cd bioavailability, mobility, and distribution in plants, various morphometric measurements, and physiological performances as photosynthesis, transpiration, water use efficiency, and pigment content were tested. The highest Cd accumulation was evident after 60 days of growing, in plants subjected to combined treatment of CA with a higher dose of Cd. Application of CA showed a beneficial effect in maintaining the photosynthetic rate as well as gas exchange capacity in willows grown in Cd-contaminated soil. Furthermore, CA slightly increased plant growth and biomass production, depending on applied Cd dose and harvest period. A chelating agent like CA showed strong influence in plant response to combat Cd toxicity.
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http://dx.doi.org/10.1080/15226514.2019.1633999DOI Listing
December 2019

Body Weight Parameters are Related to Morbidity and Mortality After Liver Transplantation: A Systematic Review and Meta-analysis.

Transplantation 2019 11;103(11):2287-2303

Institute of Nursing Science, Department Public Health, University of Basel, Basel, Switzerland.

Background: Weight gain and obesity are well-known clinical issues in liver transplantation (LTx). However, their impacts on patient outcomes remain unclear, as only the impact of pre-LTx body mass index (BMI) on survival has been meta-analyzed. We summarized and synthesized the evidence on pre- and post-LTx body weight parameters' relations with post-LTx outcomes such as survival, metabolic and cardiovascular comorbidities, and healthcare utilization.

Methods: We followed the Cochrane Handbook for Systematic Reviews of Interventions' recommendations. Quality was assessed via a 19-item instrument. Odds ratios and 95% confidence intervals were calculated for outcomes investigated in ≥5 studies.

Results: Our meta-analysis included 37 studies. Patients with pre-LTx BMI ≥ 30 kg/m and BMI ≥ 35 kg/m had lower overall survival rates than those with pre-LTx normal weight (72.6% and 69.8% versus 84.2%; P = 0.02 and P = 0.03, respectively). Those with pre-LTx BMI ≥ 30 kg/m had worse overall graft survival than normal weight patients (75.8% and 85.4%; P = 0.003). Pre-LTx BMI and pre-LTx overweight were associated with new-onset diabetes (P < 0.001 and P = 0.015, respectively), but post-LTx BMI showed no relationship. No associations were evident with healthcare utilization.

Conclusions: Patients with BMI values ≥30 kg/m had worse patient and graft survival than those with normal weight. Few of the reviewed studies examined post-LTx body weight parameters or other relevant outcomes such as cardiovascular comorbidities. High heterogeneity as well as diverse definitions and operationalizations of measurement and outcomes severely impeded comparability.
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http://dx.doi.org/10.1097/TP.0000000000002811DOI Listing
November 2019

Primary defects in lipid handling and resistance to exercise in myotubes from obese donors with and without type 2 diabetes.

Appl Physiol Nutr Metab 2020 Feb 5;45(2):169-179. Epub 2019 Jul 5.

Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo 0316, Norway.

Several studies have shown that human primary myotubes retain the metabolic characteristic of their donors in vitro. We have demonstrated, along with other researchers, a reduced lipid turnover and fat oxidation rate in myotubes derived from obese donors with and without type 2 diabetes (T2D). Because exercise is known to increase fat oxidative capacity in skeletal muscle, we investigated if in vitro exercise could restore primary defects in lipid handling in myotubes of obese individuals with and without T2D compared with lean nondiabetic donors. Primary myotubes cultures were derived from biopsies of lean, obese, and T2D subjects. One single bout of long-duration exercise was mimicked in vitro by electrical pulse stimulation (EPS) for 24 h. Lipid handling was measured using radiolabeled palmitate, metabolic gene expression by real-time qPCR, and proteins by Western blot. We first showed that myotubes from obese and T2D donors had increased uptake and incomplete oxidation of palmitate. This was associated with reduced mitochondrial respiratory chain complex II, III, and IV protein expression in myotubes from obese and T2D subjects. EPS stimulated palmitate oxidation in lean donors, while myotubes from obese and T2D donors were refractory to this effect. Interestingly, EPS increased total palmitate uptake in myotubes from lean donors while myotubes from T2D donors had a reduced rate of palmitate uptake into complex lipids and triacylglycerols. Myotubes from obese and T2D donors are characterized by primary defects in palmitic acid handling. Both obese and T2D myotubes are partially refractory to the beneficial effect of exercise on lipid handling.
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http://dx.doi.org/10.1139/apnm-2019-0265DOI Listing
February 2020

Growth, physiology, and phytoextraction potential of poplar and willow established in soils amended with heavy-metal contaminated, dredged river sediments.

J Environ Manage 2019 Jun 25;239:352-365. Epub 2019 Mar 25.

Institute of Lowland Forestry and Environment, University of Novi Sad, Novi Sad, Serbia.

Phytotechnologies have been used worldwide to remediate and restore damaged ecosystems, especially those caused by industrial byproducts leaching into rivers and other waterways. The objective of this study was to test the growth, physiology, and phytoextraction potential of poplar and willow established in soils amended with heavy-metal contaminated, dredged river sediments from the Great Bačka Canal near Vrbas City, Serbia. The sediments were applied to greenhouse-grown trees of Populus deltoides Bartr. ex Marsh. clone 'Bora' and Salix viminalis L. clone 'SV068'. Individual pots with trees previously grown for two months were amended with 0, 0.5 and 1.0 kg of sediment containing 400 mg Cr kg, 295 mg Cu kg, 465 mg Zn kg, 124 mg Ni kg, 1.87 mg Cd kg, and 61 mg Pb kg. Following amendment, trees were grown for two seasons (i.e., 2014, 2015), with coppicing after the first season. In addition to growth parameters, physiological traits related to the photosynthesis and nitrogen metabolism were assessed during both growing seasons. At the end of the study, trees were harvested for biomass analysis and accumulation of heavy metals in tree tissues and soils. Application of sediment decreased aboveground biomass by 37.3% in 2014, but increased height (16.4%) and leaf area (19.2%) in 2015. Sediment application negatively impacted the content of pigments and nitrate reductase activity, causing them to decrease over time. Generally, the effect of treatments on growth was more pronounced in poplars, while willows had more pronounced physiological activity. Accumulation patterns were similar to previously-published results. In particular, Zn and Cd were mostly accumulated in leaves of both poplar and willow, which indicated successful phytoextraction. In contrast, other metals (e.g., Cr, Ni, Pb, Cu) were mostly phytostabilized in the roots. Differences in metal allocation between poplar and willow were recorded only for Cu, while other metals followed similar distribution patterns in both genera. Results of this study indicated that the composition of heavy metals in the sediments determined the mechanisms of the applied phytoremediation technique.
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http://dx.doi.org/10.1016/j.jenvman.2019.03.072DOI Listing
June 2019

Significance of *28 Genotype in Patients with Advanced Liver Injury Caused By Chronic Hepatitis C.

J Med Biochem 2019 Mar 1;38(1):45-52. Epub 2019 Mar 1.

Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia.

Background: Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse.

Methods: Genetic testing of TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging.

Results: *28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p=0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of genotype in CHC patients with severe liver injury.

Conclusions: Frequencies of genotype are high in both Serbian CHC patients and healthy subjects. The presence of genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.
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http://dx.doi.org/10.2478/jomb-2018-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298452PMC
March 2019

Prevalence of oncogenic Human papillomavirus and genetic diversity in the L1 gene of HPV16 HPV 18 HPV31 and HPV33 found in women from Vojvodina Province Serbia.

Biologicals 2019 Mar 20;58:57-63. Epub 2019 Feb 20.

Department of Gynecology, Community Health Centre, Novi Sad, Serbia.

The main purpose of this paper is to estimate the pre-vaccination prevalence of 12 hrHPV types among 564 women from Vojvodina province (Serbia). The corrected contingency coefficient (Ccorr) was used to estimate the importance of association of examined HPV types and cytological diagnosis. The highest association with the abnormal cytology was observed for HPV 16 (Ccorr = 0.493) in all age groups of participants. The effect of HPV 16 was especially clear within the group of women older than 35 years (Ccorr = 0.691), compared with women younger than 35 (Ccorr = 0.333). The molecular characterization at the level of L1 gene of HPV 16, 18, 31 and 33 variants was for the first time assessed in our region. Nearly all HPV 16 isolates cluster with variant lineage A (96.4%) the remaining isolates clustering with variant lineage D. All of HPV 18 and HPV 33 isolates are clustering within the lineage A while isolates of HPV 31 group with lineages A and C. This contributes to understanding of intrinsic geographical and biological differences of examined HPV types and could be useful for development of cervical cancer screening strategies in Vojvodina (Serbia) and diagnosis of HPV related cervical cancer in general.
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http://dx.doi.org/10.1016/j.biologicals.2019.02.001DOI Listing
March 2019

Pre- and post-transplant factors associated with body weight parameters after liver transplantation - A systematic review and meta-analysis.

Transplant Rev (Orlando) 2019 01 12;33(1):39-47. Epub 2018 Oct 12.

Institute of Nursing Science, Department Public Health, University of Basel, Bernoullistrasse 28, CH-4056 Basel, Switzerland; Academic Center for Nursing and Midwifery, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. Electronic address:

Background: Weight gain and obesity can increase liver transplant (LTx) recipients' disease burden. We aimed to summarize and synthesize the evidence on pre- and post-transplant factors related to post-LTx BMI, weight gain, and obesity.

Methods: For this systematic review and meta-analysis we searched Medline (PubMed), Cochrane library, CINAHL, PsycINFO, and EMBASE for quantitative studies on 6 classes of factors (i.e., genetic, sociodemographic, behavioral, biomedical, psychological, and environmental) linked to body weight parameters in adult first-time LTx patients. A 19-item instrument was used for quality assessment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for relationships investigated in ≥5 studies. Factors investigated in <5 studies were summarized and described.

Results: Of 16,495 articles retrieved, 43 assessed factors in LTx. These examined 82 mainly biomedical and sociodemographic factors. However, variation between definitions allowed inclusion of only 2 factors (i.e., tacrolimus, cyclosporine) in our meta-analyses of 6 studies examining a shared parameter for body weight (median patient sample: 171 (range: 63-455); Europe n = 3; United States n = 3; publication years: 1997-2015). Neither tacrolimus (OR, 0.75; 95% CI, 0.47-1.21; p = 0.24) nor cyclosporine (OR, 1.40; 95% CI, 0.89-2.18; p = 0.14) were related significantly with post-LTx obesity.

Conclusions: Evidence on modifiable factors related to post-LTx body weight parameters is still scarce, as definition variability limits data extraction and pooling for meta-analyses. To facilitate future research, studies should apply theoretical frameworks to guide their study design, select variables of interest and systematically examine interrelationships among selected factors.
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http://dx.doi.org/10.1016/j.trre.2018.10.002DOI Listing
January 2019

Electrical Pulse Stimulation of Primary Human Skeletal Muscle Cells.

Methods Mol Biol 2019 ;1889:17-24

Department of Life Sciences and Health, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.

Electrical pulse stimulation (EPS) is an in vitro method of inducing contractions in cultured skeletal muscle cells of human and animal origin. Motor neuron activation of muscle fibers can be replaced by applying EPS on differentiated skeletal muscle cells (myotubes) in culture (Thelen et al. Biochemical J 321:845-848, 1997, Fujita et al. Exp Cell Res 313:1853-1865, 2007).Here we describe two protocols for EPS of human myotubes in 6-well plates: acute, high-frequency (single bipolar pulses of 2 ms, 100 Hz for 200 ms every fifth second for 5-60 min, 10-30 V) and chronic, low-frequency (single bipolar pulses of 2 ms, 1 Hz 10-30 V for 48 h) at the end of a 7 days long differentiation.
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http://dx.doi.org/10.1007/978-1-4939-8897-6_2DOI Listing
June 2019

Heavy metal accumulation in vegetable species and health risk assessment in Serbia.

Environ Monit Assess 2018 Jul 11;190(8):459. Epub 2018 Jul 11.

Faculty of Sciences, Department for Biology and Ecology, University of Novi Sad, Trg Dositeja Obradovica 3, Novi Sad, 21000, Serbia.

Continuous monitoring of heavy metal content in vegetables is of high priority for population nutrition control, as well as risk assessment for human health. The chemical composition of plants is a reliable indicator of their contamination by hazardous substances accumulated in the environment as a consequence of inadequately applied agro-technology. The main goal of this study was to examine the quality of vegetables that reach consumer markets as a function of growth location. Samples of 11 of the most common vegetable species used in the human diet were collected during a 4-year survey. Vegetables originated from local farm producers who cultivated them at different locations in Vojvodina Province, Serbia. Many vegetable samples contained disturbingly high levels of the investigated metals: cadmium, lead, nickel, and chromium. The plant species with the highest Cd accumulation was spinach, where Cd leaves exceeded the maximum permissible concentrations (MPCs) in more than half of the analyzed samples from different localities (54%). Pb concentrations in spinach were also higher than MPC values (according to Serbian law 3.0 μg/g) in 46% of all analyzed samples. Results showed that Cr levels in all tested vegetable species were below MPC values recommended by the FAO/WHO organization. The largest chromium accumulator was spinach, with average values of 2.3 μg/g, followed by beetroot and parsnips with an average concentration of 1.4 μg/g. The highest average content of Ni in all analyzed vegetable species was also recorded in spinach leaves, with an average value of 2.2 μg/g, followed by broccoli (1.7 μg/g) and tomatoes (1.5 μg/g).
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http://dx.doi.org/10.1007/s10661-018-6743-yDOI Listing
July 2018

Utilization of lactic acid in human myotubes and interplay with glucose and fatty acid metabolism.

Sci Rep 2018 06 29;8(1):9814. Epub 2018 Jun 29.

Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.

Once assumed only to be a waste product of anaerobe glycolytic activity, lactate is now recognized as an energy source in skeletal muscles. While lactate metabolism has been extensively studied in vivo, underlying cellular processes are poorly described. This study aimed to examine lactate metabolism in cultured human myotubes and to investigate effects of lactate exposure on metabolism of oleic acid and glucose. Lactic acid, fatty acid and glucose metabolism were studied in myotubes using [C(U)]lactic acid, [C]oleic acid and [C(U)]glucose, respectively. Myotubes expressed both the MCT1, MCT2, MCT3 and MCT4 lactate transporters, and lactic acid was found to be a substrate for both glycogen synthesis and lipid storage. Pyruvate and palmitic acid inhibited lactic acid oxidation, whilst glucose and α-cyano-4-hydroxycinnamic acid inhibited lactic acid uptake. Acute addition of lactic acid inhibited glucose and oleic acid oxidation, whereas oleic acid uptake was increased. Pretreatment with lactic acid for 24 h did not affect glucose or oleic acid metabolism. By replacing glucose with lactic acid during the whole culturing period, glucose uptake and oxidation were increased by 2.8-fold and 3-fold, respectively, and oleic acid oxidation was increased 1.4-fold. Thus, lactic acid has an important role in energy metabolism of human myotubes.
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http://dx.doi.org/10.1038/s41598-018-28249-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026123PMC
June 2018

FIB-4 and APRI scores for predicting severe fibrosis in chronic hepatitis C - a developing country's perspective in DAA era.

J Infect Dev Ctries 2018 Mar 31;12(3):178-182. Epub 2018 Mar 31.

Clinical Centre of Serbia, Belgrade, Serbia.

Introduction: Chronic Hepatitis C Virus (HCV) infection leads to progressive fibrosis making fibrosis staging necessary in the evaluation of such patients. Different fibrosis scores are emerging as possible non-invasive alternatives for liver biopsy. The Fibrosis-4 Index (FIB-4) and AST to Platelet Ratio Index (APRI) scores are the most widely used and the most extensively tested. This study aims to determine if it was possible to accurately use these to identify patients that are unlikely to have severe fibrosis.

Methodology: One hundred and forty-two patients with chronic hepatitis C infection who underwent liver biopsy since January 1st 2014 until May 31st 2017 at the Hospital for Infectious and Tropical Diseases in Belgrade were analyzed. The FIB-4 and APRI scores were calculated for each patient and compared to histologically determined fibrosis stage.

Results: A comprehensive statistical analysis was conducted in order to compare patients with and without severe fibrosis and to evaluate the accuracy of the fibrosis scores. Patients with non-severe fibrosis were younger, had higher platelet counts and lower transaminase levels. FIB-4 had an AUC of 0.875 and the APRI score had an AUC of 0.861. No patients with severe fibrosis or cirrhosis had a FIB-4 lower than 1.08. FIB-4 was superior to APRI in identifying patients with severe fibrosis in the study cohort.

Conclusion: FIB-4 was superior to APRI in the recognition of severe fibrosis. FIB-4 may prove very useful in identifying patients without advanced liver disease, especially if other non-invasive methods are inaccessible.
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http://dx.doi.org/10.3855/jidc.10190DOI Listing
March 2018

The prevalence and the risk factors for hepatitis C virus infection in Serbia.

J Infect Dev Ctries 2018 Mar 31;12(3):171-177. Epub 2018 Mar 31.

Clinical Center of Serbia, Belgrade, Serbia.

Introduction: The epidemiological characteristics of the hepatitis C virus (HCV) infection in Republic of Serbia have not been studied sufficiently so far. The aim of this study was to estimate the prevalence of anti-HCV positivity in the general population of Serbia and determine the risk factors for this infection.

Methodology: Estimation of the prevalence was done using the median ratio method with data from several regional countries to a previously determined prevalence of anti-HCV positivity among volunteer blood donors of 0.19%. In order to determine the risk factors a matched case-control study was conducted of 106 subjects with confirmed HCV infection from the Clinic for Infectious and Tropical Diseases, Clinical Center of Serbia and the same number of hospital controls matched by sex and age.

Results: The estimated prevalence of anti-HCV positivity in the general population of Serbia was 1.13% (95% CI: 1.0-1.26%). The most important predictive risk factors of HCV infection were: intravenous drug use (OR = 31.0; 95% CI: 3.7-259.6), blood transfusions (OR = 3.7; 95% CI: 1.6-8.7), invasive dental treatment (OR = 3.1; 95% CI: 1.4-6.8), and low level of education (OR = 2.2; 95% CI:1.1-4.7). A total of 91.5% of the persons with hepatitis C had at least one of the significant risk factors.

Conclusion: The prevalence of anti-HCV positivity ranks Serbia in the range of mid-endemic European countries. Preventive measures should be directed at preventing drug use, on education about getting the infection, creating safe conditions for blood transfusions, and strict adherence to adopted practices in dentistry.
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http://dx.doi.org/10.3855/jidc.10172DOI Listing
March 2018

Correction to: Antifungal activity of Myrtus communis against Malassezia sp. isolated from the skin of patients with pityriasis versicolor.

Infection 2018 04;46(2):287

Department of Biomedical Sciences, University of Sassari, V. le San Pietro 43/C, 07100, Sassari, Italy.

The original version of this article unfortunately contained two mistakes in authors' names.
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http://dx.doi.org/10.1007/s15010-017-1104-2DOI Listing
April 2018

Antifungal activity of Myrtus communis against Malassezia sp. isolated from the skin of patients with pityriasis versicolor.

Infection 2018 Apr 20;46(2):253-257. Epub 2017 Nov 20.

Department of Biomedical Sciences, University of Sassari, V. le San Pietro 43/C, 07100, Sassari, Italy.

The increasing incidence of fungal infections and antifungal resistance has prompted the search for novel antifungal drugs and alternative agents. We explored the antifungal activity of Myrtus communis essential oil (EO) against Malassezia sp. isolated from the skin of patients with pityriasis versicolor. These broad-spectrum antimicrobial activities of M. communis EO and its potent inhibiting activity on Malassezia growth deserve further research with aim to considerate this EO as candidate for topical use in treatment of skin diseases.
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http://dx.doi.org/10.1007/s15010-017-1102-4DOI Listing
April 2018

Procalcitonin in heart failure: hic et nunc.

Biomark Med 2017 Oct 4;11(10):893-903. Epub 2017 Oct 4.

Department of Cardiology, Zvezdara University Medical Center, Belgrade, Serbia.

Although procalcitonin (PCT) was evaluated for the first time in the setting of heart failure (HF) in 1999, its utility in HF patients is still under examination. Patients with HF have significantly higher plasma PCT concentrations than healthy subjects and PCT levels are associated with severity of HF. It has been confirmed that higher levels of PCT are associated with worse outcomes, such as increased mortality and higher rate of rehospitalization, in HF patients with no evidence of infection. Furthermore, it has been approved that PCT-guided antibiotic treatment in HF patients reduces duration of antibiotic therapy and improves outcomes. This review summarizes current evidence from the published literature of the usefulness and limitations of PCT as a biomarker in HF.
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http://dx.doi.org/10.2217/bmm-2017-0160DOI Listing
October 2017

[Not Available].

Krankenpfl Soins Infirm 2017 Feb;110(1):14-17

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February 2017

Evolution of body weight parameters up to 3 years after solid organ transplantation: The prospective Swiss Transplant Cohort Study.

Clin Transplant 2017 03 24;31(3). Epub 2017 Jan 24.

Institute of Nursing Science, University of Basel, Basel, Switzerland.

Obesity and weight gain are serious concerns after solid organ transplantation (Tx); however, no unbiased comparison regarding body weight parameter evolution across organ groups has yet been performed. Using data from the prospective nationwide Swiss Transplant Cohort Study, we compared the evolution of weight parameters up to 3 years post-Tx in 1359 adult kidney (58.3%), liver (21.7%), lung (11.6%), and heart (8.4%) recipients transplanted between May 2008 and May 2012. Changes in mean weight and body mass index (BMI) category were compared to reference values from 6 months post-Tx. At 3 years post-Tx, compared to other organ groups, liver Tx recipients showed the greatest weight gain (mean 4.8±10.4 kg), 57.4% gained >5% body weight, and they had the highest incidence of obesity (38.1%). After 3 years, based on their BMI categories at 6 months, normal weight and obese liver Tx patients, as well as underweight kidney, lung and heart Tx patients had the highest weight gains. Judged against international Tx patient data, the majority of our Swiss Tx recipients' experienced lower post-Tx weight gain. However, our findings show weight gain pattern differences, both within and across organ Tx groups that call for preventive measures.
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http://dx.doi.org/10.1111/ctr.12896DOI Listing
March 2017

Risk factors for severe influenza A virus infections in post-2009 pandemic period.

Srp Arh Celok Lek 2016 Nov-Dec;144(11-12):626-32

Introduction: Literature data concerning risk factors for severe influenza in post-2009 pandemic period, from low- and middle-income Central and Eastern European countries are very limited.

Objective: The aim of this study was to investigate the risk factors for severe A(H1N1)pdm09 and A(H3N2) influenza during the post-2009 pandemic period.

Methods: During four consecutive seasons of 2010/2011–2013/2014, nasopharyngeal or nasal and pharyngeal swab samples from 153 patients with mild and 147 patients with severe influenza were tested using real-time reverse transcription polymerase chain reaction (real-time RT PCR) assays.

Results: The study indicated three statistically significant risk factors of influenza severity, including presence of chronic underlying illness/condition [odds ratio (OR) of 15.2, 95% confidence interval (CI) of 1.8–125.4, p = 0.001), age ≥15 years (OR 9.2, 95% CI 3.5–24.1, p < 0.001), and delay in medical care of more than two days after the symptoms onset (OR 3.2, 95% CI 1.6–6.4, p = 0.001).

Conclusion: Obtained results confirmed that patients with chronic underlying illness/condition and older than 15 years had the highest risk for serious complications from influenza and highlighted the importance of start of antiviral therapy within the first two days of illness in order to reduce the risk for the most severe outcomes of influenza, such as acute respiratory distress syndrome and lethal outcome.
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May 2018

Perceived Health-Related Quality of Life in Women With Vulvar Neoplasia: A Cross Sectional Study.

Int J Gynecol Cancer 2016 09;26(7):1313-9

*Institute for Applied Nursing Sciences IPW, University of Applied Sciences FHS St. Gallen, St. Gallen; †Departement of Neurosurgery, University Hospital Zurich, Zürich, Switzerland; ‡Hechinger Nursing GmbH, Munich, Germany; §Institute of Nursing Science, University of Basel, Basel, Switzerland; ‖Department of Obstetrics and Gynaecology, Universitätsklinikum Düsseldorf, Düsseldorf, Germany; ¶Department of Gynecology and Obstetrics, Bern University Hospital, Bern, Switzerland; #Institute for Nursing Science IPW, University of Applied Sciences FHS St. Gallen, St. Gallen, Switzerland; and **Sydney Nursing School, University of Sydney, Sydney, Australia.

Objective: The aim of the study was to determine health-related quality of life (HRQoL) of women with surgically treated vulvar intraepithelial neoplasia (VIN) and vulvar cancer (VC) during the first week after hospital discharge. Further objectives were to investigate differences between women with VIN and VC as well as to examine whether correlations exist between women's symptom experience and HRQoL.

Methods: This cross-sectional study was conducted in 8 hospitals in Germany and Switzerland. Women with VIN and VC rated HRQoL with the validated German Short-Form 36. Differences between HRQoL in women with VIN and VC were tested with Wilcoxon rank-sum score. The WOMen with vulvAr Neoplasia (WOMAN) - Patient reported Outcome (PRO) self-report instrument was used to measure women's symptom experience. Correlations between symptoms and HRQoL were calculated using Spearman correlation coefficient.

Results: Women with VIN and VC (n = 65) reported lower HRQoL in physical aspects (Physical Component Summary [PCS], 34.9) than that in mental aspects (Mental Component Summary, 40.5). Women with VC had lower HRQoL than women with VIN, as manifested by significant differences concerning the dimensions of "physical functioning" and "role-physical." "Difficulties in daily life" as a distressing symptom correlated with MCS and PCS. Wound-related symptoms correlated with PCS and psychosocial symptoms/issues with MCS.

Conclusions: Analysis showed that women with vulvar neoplasia reported lower HRQoL in the physical and mental dimensions 1 week after discharge than comparable studies referring to months or years after surgery. Health-related quality of life is influenced by physical impairment because physical symptoms are prevalent 1 week after discharge. Patient education should focus on symptom management in an early postsurgical phase to enhance women's HRQoL.
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http://dx.doi.org/10.1097/IGC.0000000000000770DOI Listing
September 2016

Frequency of twelve carcinogenic human papilloma virus types among women from the South Backa region, Vojvodina, Serbia.

Turk J Med Sci 2016 Jan 5;46(1):97-104. Epub 2016 Jan 5.

Faculty of Medicine, University of Novi Sad, Serbia.

Background/aim: The aim of this study was to determine the presence and age distribution of different oncogenic human papilloma virus (HPV) types in women in the South Backa region and its relationship to Pap results.

Materials And Methods: In a group of 1087 women with normal and abnormal cytology, the commercial HR HPV Real-TM kit (Sacace Biotechnologies, Italy) was used.

Results: Overall, 50.5% of the women were HPV positive. The presence of HPV types 18, 31, 51, and 58 was significantly influenced by age, while the presence of HPV types 16 and 45 was significantly influenced by cervical cytology. Results of the LSD test show a wide spectrum of high risk HPV among women with normal cytology and women with a low grade cervical lesion rate (atypical squamous cell of undetermined significance (ASCUS) and low grade squamous intraepithelial lesions (LSIL). The most prevalent HPV types found were 16, 31, 51, 18, and 52. In the HSIL group the most prevalent HPV types were 16 and 45.

Conclusion: The reported results provide new data on the circulation of oncogenic HPV genotypes and frequency of multiple infections among women in Vojvodina and suggest that a prophylactic vaccine against HPV 16 and 18 has the potential to prevent approximately half of the high-grade lesions.
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http://dx.doi.org/10.3906/sag-1410-47DOI Listing
January 2016

Influenza B Viruses in the Population of Province of Vojvodina during the 2012/2013 Season: Differentiation of B/Yamagata and B/Victoria Lineages by Real-time RT-PCR, Antigenic and Phylogenetic Characterization.

Srp Arh Celok Lek 2015 Jul-Aug;143(7-8):429-37

Introduction: At present, two phylogenetically distinct influenza B virus lineages, B/Yamagata and B/ Victoria, co-circulate worldwide and can cause significant morbidity and mortality.

Objective: The aim of this study was to determine the prevalences of two influenza B virus lineages in the population of Vojvodina and to identify their antigenic and phylogenetic properties.

Methods: A total of 369 and 334 nasopharyngeal, or nasal/throat swab samples, collected during the 2012/2013 and 2013/2014 seasons, respectively, were tested using specific singleplex influenza A, influenza B, influenza B/Yamagata and influenza B/Victoria real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Antigenic and genetic testing were done by hemagglutination inhibition assay and hemagglutinin and neuraminidase gene sequence analysis, respectively.

Results: During the 2012/2013 season, influenza B viruses were present in 53.4% (101/189) of influenza positive samples.The B/Yamagata-like viruses (81.2%) significantly predominated over the B/Victoria-like viruses (18.8%). Comparing to B/Victoria-like positive patients, among B/Yamagata-like positive patients, children 5-14 years of age were significantly more represented (5.3% vs. 35.4%, respectively), as well as patients with mild form of illness (15.8% vs. 45.1%, respectively). The results of sequence analysis and antigenic testing showed that tested viruses were not closely related to B/Wisconsin/1/2010, the vaccine virus for 2012/2013. During the 2013/2014 season influenza B viruses were not detected.

Conclusion: The results of this study confirmed the health significance of influenza B viruses and indicated that B/Yamagata-like viruses were significantly more prevalent than B/Victoria lineage viruses, during the 2012/2013 season. They also showed a sub-optimal match between the tested viruses and the vaccine virus for season 2012/2013.
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http://dx.doi.org/10.2298/sarh1508429rDOI Listing
December 2015