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1.  The impact of ACE gene polymorphism on the incidence and phenotype of sarcoidosis in rural and urban settings 
Archives of Medical Science : AMS  2015;12(6):1263-1272.
Introduction
Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients’ environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings.
Material and methods
The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes.
Results
Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis.
Conclusions
Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution.
doi:10.5114/aoms.2015.48966
PMCID: PMC5108373  PMID: 27904517
sarcoidosis; ACE gene; polymorphism; T lymphocytes; environment
2.  A new diagnostic tool for masked hypertension: impaired sleep quality 
Archives of Medical Science : AMS  2016;12(6):1207-1213.
Introduction
The aim of this study was to evaluate the relationship between masked hypertension and impaired sleep quality. Additionally, we evaluated the diagnostic role and prevalence of poor sleep quality among patients with newly diagnosed masked hypertension.
Material and methods
A total of 112 individuals, 72 patients with newly diagnosed masked hypertension and 40 normotensive healthy volunteers, were included in this study. All patients underwent evaluation comprising 12-lead electrocardiography, transthoracic echocardiography, 24-hour Holter ECG, and basic laboratory tests. Additionally, all participants completed questionnaires, including the Pittsburgh Sleep Quality Index (PSQI).
Results
The total PSQI score was significantly higher in the masked hypertension group than in the normotensive healthy volunteers (4.13 ±2.43 vs. 2.33 ±1.67, p < 0.001). A PSQI score > 5 was found in 45.8% (n = 33) of patients in the masked hypertension group and 15% (n = 6) of patients in the normotensive group (p < 0.001). The non-dipper pattern was found in 17.5% of the healthy volunteer group and 59.94% (n = 41) of the masked hypertension group (p < 0.001). When we compared the dipping pattern of the masked hypertension groups, there was a significant difference in PSQI score between the dipper and non-dipper groups (4.87 ±3.21 vs. 3.58 ±2.33, p < 0.001). Multiple logistic regression analyses showed that masked hypertension, LV mass, and LV mass index score were independent predictors of poor PSQI.
Conclusions
This study demonstrates impaired sleep quality in subjects with masked hypertension, particularly those with a non-dipper pattern. Additionally, this study indicates that impaired sleep quality may help diagnose masked hypertension, particularly in the non-dipper group.
doi:10.5114/aoms.2015.51177
PMCID: PMC5108374  PMID: 27904509
masked hypertension; sleep quality; sleep disturbances
3.  Integration of medical therapy and mechanical circulatory support in the management of acute heart failure 
Archives of Medical Science : AMS  2015;12(6):1317-1323.
Acute heart failure is still characterized by poor prognosis with high mortality. Diagnosis is based on clinical symptoms and hemodynamic measurements. Early coronary revascularization in cardiogenic shock complicating myocardial infarction improves outcome. The further contemporary therapeutic options in the management of acute heart failure are limited to a merely symptomatic effect with relief of dyspnea, reduction of volume overload and improvement of hemodynamic parameters by vasodilators (in hypertension) or inotropic and vasopressor agents (in hypotension). However, so far no medical therapy has been shown to positively affect clinical outcomes of patients with acute heart failure. Early identification of impending circulatory collapse coupled with rapid implementation of mechanical circulatory support may contribute to mortality reduction as a combined concept of the management of acute heart failure.
doi:10.5114/aoms.2015.51700
PMCID: PMC5108375  PMID: 27904524
acute heart failure; cardiogenic shock; coronary revascularization; medical therapy; mechanical circulatory support
4.  Effect of Th1/Th2 cytokine administration on proinflammatory SKOV-3 cell activation 
Archives of Medical Science : AMS  2015;12(6):1337-1347.
Introduction
Interleukin(IL)-1β, IL-6 and IL-12 might associate with inflammatory processes in a tumor progression and create a specific microenvironment for tumor growth. The aim of the study was to assess whether the Th1 and Th2 type cytokines, such as IL-2 and IL-10, affect ovarian carcinoma continuous cell line (SKOV-3) pro-inflammatory activation.
Material and methods
SKOV-3 ovarian cells and peripheral blood mononuclear cells (PBMCs) were stimulated by IL-2 and IL-10. Additionally, SKOV-3 ovarian cells and PBMCs were co-cultured together. Proinflammatory activation of cancer cells was evaluated by measurement of IL-1β and IL-6 levels in culture fluid after 72 h of incubation.
Results
SKOV-3 cells and PBMCs secreted IL-1β and IL-6. After stimulation by IL-2 and IL-10, secretion of studied parameters was changed in a dose-dependent manner. The addition of a higher IL-2 level gave rise to an increase of IL-1β, IL-6 and IL-12 secretion in SKOV-3 cells. Stimulation by IL-10 increased only IL-1β secretion in SKOV-3 cells. However, IL-6 secretion decreased after stimulation with 25 ng/ml IL-10. Activatory effects of IL-2 and inhibitory effects of IL-10 in co-culture of SKOV-3 and PBMCs were observed.
Conclusions
Our results suggested that Th1/Th2 type of cytokines might influence pro-inflammatory activation of SKOV-3 ovarian cells. Co-cultures of SKOV-3 and PBMCs showed significant changes in cross-talk between cancer and immune cells.
doi:10.5114/aoms.2015.53143
PMCID: PMC5108376  PMID: 27904527
IL-1β; IL-6; IL-12; ovarian cancer SKOV-3 cells; Th1-Th2 cytokines
5.  Relationship between visual status and functional status and the risk of falls in women. The RAC-OST-POL study 
Archives of Medical Science : AMS  2016;12(6):1232-1238.
Introduction
Falls in elderly women producing fractures are a public health problem that could be largely preventable. The aim of this study was to determine the effect of visual impairment on functional status, falls and fractures in women.
Material and methods
We examined 623 women aged ≥ 55 years in order to assess the association between visual status and functional status and the risk of falls and fractures. Distance, near visual acuity, and depth perception were examined. Functional status was assessed using the Instrumental Activities of Daily Living (IADL) and Timed Up and Go (TUG) tests. The history of falls in the last 12 months and prior osteoporotic fractures were recorded.
Results
The mean age of participants was 66.01 ±7.76 years. Distance visual acuity was correlated (r = –0.13, p < 0.0001) with an increased number of falls. The most prognostic fall factor was IADL (Z = 3.19, p < 0.05), which showed a significant association with distance acuity (r = 0.27, p < 0.0001). The TUG test time significantly increased with diminishing visual acuity: 10.6 ±3.1 s for good, 12.8 ±6.1 s for moderate and 15.3 ±8.8 s for poor visual acuity (p < 0.0001, ANOVA 24.4). The IADL also differs significantly (p < 0.0001) in subgroups divided according to visual acuity (23.6 ±1.5, 22.6 ±2.9, 21.2 ±4.8 points, respectively). In multivariate logistic regression on probability of falls including IADL, TUG and visual acuity, IADL was found to be an independent prognostic factor (p = 0.025). The data revealed no association of refractive correction, depth perception, or near visual acuity with fall incidence or history of fractures.
Conclusions
Visual acuity influences functional status and number of falls in women aged over 55 years.
doi:10.5114/aoms.2015.55146
PMCID: PMC5108377  PMID: 27904513
vision; fall; Instrumental Activities of Daily Living; women
6.  Neuroprotective effects of erythropoietin against oxidant injury following brain irradiation: an experimental study 
Archives of Medical Science : AMS  2016;12(6):1348-1353.
Introduction
Radiation therapy (RT) is a major treatment modality, and the central nervous system is a dose-limiting organ in clinical RT. This experimental study aims to present the evaluation of the neuroprotective effects of erythropoietin (EPO) against oxidant injury following brain irradiation in rats.
Material and methods
Forty Wistar rats were randomly assigned to four groups (n = 10 each). In group 1 the rats received no EPO and underwent sham RT. The rats in groups 2 and 3 received EPO. In group 2 rats underwent sham RT, while in group 3 rats received RT. The rats in group 4 received no EPO and underwent RT. Rats were irradiated using a Cobalt-60 teletherapy machine using a single fraction of 20 Gy covering the whole brain. Cervical dislocation euthanasia was performed. The nitrite and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) and glutathione peroxidase (GSHPX) activities were evaluated in dissected brain tissues.
Results
The nitrite and MDA levels were higher in the RT group (2.10 ±0.62 ppm, 26.02 ±2.16 nmol/ml; p < 0.05) and lower in the EPO + RT group (1.45 ±0.12 ppm, 25.49 ±1.90 nmol/ml; p < 0.05). The SOD and GSHPX activity was higher in the EPO + RT group (2.62 ±0.49 U/mg, 1.75 ±0.25 U/mg, p < 0.05).
Conclusions
This study supports the probable neuroprotective effects of EPO against oxidant injury following brain irradiation in a rat model, presumably through decreasing free radical production and increasing expression of antioxidant enzymes.
doi:10.5114/aoms.2016.58622
PMCID: PMC5108378  PMID: 27904528
brain; irradiation; oxidant injury; neuroprotective effects; erythropoietin
7.  Safety and efficacy of tenecteplase versus alteplase in acute coronary syndrome: a systematic review and meta-analysis of randomized trials 
Archives of Medical Science : AMS  2016;12(6):1181-1187.
Introduction
Alteplase and tenecteplase are two widely used thrombolytic agents and are both approved for the treatment of acute myocardial infarction. These two molecules have increased fibrin specificity compared with older thrombolytics but distinct pharmacokinetic properties and may differ in terms of risks and benefits. We decided to review the available evidence comparing the safety and efficacy of these two molecules in acute coronary syndrome (ACS) or pulmonary embolism (PE).
Material and methods
To compare the efficacy and safety profile of alteplase and tenecteplase, we systematically searched PubMed, Cochrane and Embase for randomized studies comparing weight-adjusted alteplase to weight-adjusted tenecteplase in patients with ACS or PE. The primary endpoint was the risk of major bleeding, and secondary endpoints were risk of intracranial haemorrhage (ICH), vessel recanalization and 30-day mortality.
Results
Three studies including 17,325 patients with ACS were included in a quantitative meta-analysis. No study compared alteplase to tenecteplase in acute PE. Tenecteplase was associated with a statistically significant reduction of the risk of major bleeding compared to alteplase (RR = 0.79; 95% CI: 0.69–0.90, p = 0.0002). The risk of intracranial haemorrhage (RR = 0.96; 95% CI: 0.71–1.31, p = 0.82) and 30-day mortality (RR = 1.02; 95% CI: 0.9–1.15) were similar in patients treated with alteplase or tenecteplase. No difference was observed in the rate of vessel recanalization.
Conclusions
The available evidence suggests that tenecteplase is associated with a reduced risk of major bleeding compared to alteplase in ACS without evidence of reduced efficacy. These results are however mainly dependent on a single study.
doi:10.5114/aoms.2016.58929
PMCID: PMC5108379  PMID: 27904506
thrombolysis; alteplase; tenecteplase; systematic review; acute coronary syndrome
8.  Testing the feasibility and safety of the Nintendo Wii gaming console in orthopedic rehabilitation: a pilot randomized controlled study 
Archives of Medical Science : AMS  2016;12(6):1273-1278.
Introduction
The Nintendo Wii game console is already used as an additional training device for e.g. neurological wards. Still there are limited data available regarding orthopedic rehabilitation. The authors’ objective was to examine whether the Nintendo Wii is an appropriate and safe tool in rehabilitation after orthopedic knee surgery.
Material and methods
A prospective, randomized, controlled study comparing standard physiotherapy vs. standard physiotherapy plus game console training (Wii group) in patients having anterior cruciate ligament (ACL) repair or knee arthroplasty was conducted. The subjects of the Wii group (n = 17; mean age: 54 ±19 years) performed simple knee exercises daily under the supervision of a physiotherapist in addition to the normal rehabilitation program. The patients of the control group (n = 13; 52 ±18 years) were treated with physiotherapy only. The participants of both groups completed a questionnaire including the International Knee Documentation Committee (IKDC) score, the Modified Cincinnati Rating System and the Tegner Lysholm Knee Score prior to the operation, before discharge from hospital and four weeks after treatment.
Results
There was no significant difference in the score results between the Wii and the control group (p > 0.05).
Conclusions
We demonstrated that physiotherapy using the Nintendo Wii gaming console after ACL reconstruction and knee arthroplasty does not negatively influence outcome. Because training with the Wii device was highly accepted by patients, we see an opportunity whereby additional training with a gaming console for a longer period of time could lead to even better results, regarding the training motivation and the outcome after orthopedic surgery.
doi:10.5114/aoms.2016.59722
PMCID: PMC5108380  PMID: 27904518
rehabilitation; Nintendo Wii; physiotherapy; orthopedic surgery
9.  Mind Conduct disorders in children with poor oral hygiene habits and attention deficit hyperactivity disorder in children with excessive tooth decay 
Archives of Medical Science : AMS  2016;12(6):1279-1285.
Introduction
Dental caries and poor oral hygiene are among the major childhood public health problems. Although dental research frequently refers to the link between these conditions and behavioural issues, little attention has been paid to understanding the reason for oral health problems from a psychiatric point of view. The aim of this study was to examine the relationship between poor oral health and hygiene and parental attitudes towards child rearing, parents’ and children’s oral hygiene behaviours, and childhood psychiatric disorders.
Material and methods
This study included 323 children aged 3–15 years. Decayed, missing, filled and decayed, extracted, filled indices, the Simplified Oral Hygiene Index, the Strengths and Difficulties Questionnaire, and the Parent Attitude Research Instrument were used in the study.
Results
We found that the subjects’ hyperactivity/inattention scores were positively correlated with poor oral health (p = 0.001) and heavy cariogenic food consumption (p = 0.040). Tooth brushing frequency was found to be significantly lower in children who have a risk for conduct/oppositional disorders than in their non-problematic peers (p = 0.001).
Conclusions
Dental health and oral hygiene behaviours have close links with psychiatric disorders and psychosocial issues. Improving cooperation between child psychiatrists and dentists seems to be important in the prevention of paediatric dental problems.
doi:10.5114/aoms.2016.59723
PMCID: PMC5108381  PMID: 27904519
child psychiatry; dental health; conduct disorder; hyperactivity
10.  New agents approved for treatment of acute staphylococcal skin infections 
Archives of Medical Science : AMS  2016;12(6):1327-1336.
Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that have been recently approved by the FDA: dalbavancin, oritavancin, and tedizolid. The mechanism of action, indications, antibacterial activity profile, microbial resistance, pharmacokinetics, clinical efficacy, adverse effects, interactions as well as available formulations and administration of each of these new antibiotics are described. Dalbavancin is a once-a-week, two-dose, long-acting intravenous bactericidal lipoglycopeptide antibiotic. Oritavancin, a lipoglycopeptide with bactericidal activity, was developed as a single-dose intravenous treatment for acute bacterial skin and skin-structure infections (ABSSSI), which offers simplifying treatment of infections. Tedizolid is an oxazolidinone-class bacteriostatic once-daily agent, available for intravenous as well as oral use. Increased ability to overcome bacterial resistance is the main therapeutic advantage of the novel agents over existing antibiotics.
doi:10.5114/aoms.2016.59838
PMCID: PMC5108382  PMID: 27904526
acute bacterial skin; skin-structure infection; anti-bacterial agents; dalbavancin; oritavancin; tedizolid
11.  The effects of vitamin D on severity of coronary artery atherosclerosis and lipid profile of cardiac patients 
Archives of Medical Science : AMS  2016;12(6):1199-1206.
Introduction
A deficiency of 25-hydroxyvitamin D (25(OH)D) (the standard biomarker for vitamin D status) can have multiple impacts on the cardiovascular system. The aim of the study was to assess of the influence of 25(OH)D on severity of coronary atherosclerosis and lipid profile.
Material and methods
The study involved prospectively 637 patients subject to coronary catheterization. The stage of coronary atherosclerosis was assessed using the Coronary Artery Surgery Study score (CASSS). Plasma concentration of 25(OH)D was measured using an electrochemiluminescent immunoassay. The levels of total cholesterol (TC), high-density cholesterol (HDL-C) and triglycerides (TG) were measured using the enzymatic method, and the concentration of low-density cholesterol (LDL-C) was calculated with the Friedewald equation.
Results
The average level of 25(OH)D was 15.85 ng/ml. A higher level of 25(OH)D was observed in men (16.28 ng/ml vs. 15.1 ng/ml; p = 0.027). The study did not reveal any significant correlation between the level of 25(OH)D and severity of coronary atherosclerosis. It was observed however that the increase of 25(OH)D level results in an increased number of patients without significant lesions in the coronary arteries. In the whole group of women and men in the age group of 70–80 years an inverse relationship was observed between the level of 25(OH) and the severity of coronary atherosclerosis. The whole study group showed a statistically significant inverse correlation of the 25(OH)D level with TC (p = 0.0057), LDL-C (p = 0.00037) and TG (p = 0.00017).
Conclusions
Women and men over 70 years showed an inverse correlation of the 25(OH)D level and the stage of coronary atherosclerosis. Deficiency of 25(OH)D affects the levels of TC, LDL-C and TG.
doi:10.5114/aoms.2016.60640
PMCID: PMC5108383  PMID: 27904508
vitamin D; coronary atherosclerosis; gender; lipid profile
12.  Anti-aggregatory effect of boswellic acid in high-fat fed rats: involvement of redox and inflammatory cascades 
Archives of Medical Science : AMS  2016;12(6):1354-1361.
Introduction
A high-fat diet is one of the main dietary factors promoting platelet aggregation. The present study was conducted to elucidate the involvement of boswellic acid (BA) on the platelet hyperaggregability in HFD-fed rats. As platelet hyperaggregability in HFD rats is closely linked to inflammation and enhanced free radical production, the present study was extended to evaluate the anti-inflammatory and anti-oxidative effect of BA on HFD-promoted platelet aggregation.
Material and methods
Rats were assigned to normal, HFD-fed, aspirin-treated (30 mg/kg), and BA-treated (250 and 500 mg/kg) groups.
Results
Boswellic acid administration in a high dose was effective in attenuating the severity of hyperlipidemia and platelet aggregation, indicated by lower collagen/epinephrine-induced platelet aggregation, as evidenced by the significant increase (p < 0.05) in the circulating platelet count and reduction in the number of thrombi in the lungs. Moreover, it attenuated the oxidative stress and the intensity of inflammatory mediators associated with platelet hyperaggregability, as evidenced by the inhibitory effects on interlukin-1β, COX-2 and tumor necrosis factor-α, indicating that the antiplatelet activity of BA is likely a consequence of controlling oxidative stress and inflammation.
Conclusions
The present data suggest that BA shows a promising anti-aggregatory effect by attenuating the enhanced hyperlipidemia, oxidative stress and inflammation associated with HFD.
doi:10.5114/aoms.2016.60675
PMCID: PMC5108384  PMID: 27904529
boswellic acid; high-fat diet; inflammation; oxidative stress; platelet aggregation; rat
13.  Impact of variants in CETP and apo AI genes on serum HDL cholesterol levels in men and women from the Polish population 
Archives of Medical Science : AMS  2016;12(6):1188-1198.
Introduction
Polymorphisms in the cholesterol ester transfer protein (CETP) gene and apolipoprotein AI (apo AI) gene are identified as the most common genetic factors influencing high-density lipoprotein cholesterol (HDL cholesterol) levels. Low HDL cholesterol is an important risk factor for cardiovascular disease. We investigated the effect of the TaqIB polymorphism of the CETP gene and the 75G/A polymorphism of the apo AI gene on the HDL cholesterol concentration in a sample of Polish adults.
Material and methods
A total of 621 subjects, 414 women and 207 men, were included in this study. Lipid levels were measured using standard protocols, and apolipoprotein AI was determined by immunoturbidimetric assay. CETP and apo AI genotyping was performed using a restriction fragment length polymorphism based method.
Results
Significantly lower HDL cholesterol concentrations were found in B1B1 homozygotes than in carriers of the B2 allele of the TaqIB polymorphism in the CETP gene among both men and women. In GG homozygotes of the 75G/A polymorphism in the apo AI gene lower HDL cholesterol levels were observed, but the difference did not reach statistical significance. A statistically significant association of low HDL cholesterol (< 25th percentile) with CETP genotypes was found in women (p < 0.0001) and in men (p = 0.0368).
Conclusions
These data demonstrate a significant impact of the TaqIB polymorphism in the CETP gene on HDL cholesterol levels in the studied Polish population, while the effect of the 75G/A polymorphism in the apo AI gene appears not to be significant.
doi:10.5114/aoms.2016.60870
PMCID: PMC5108385  PMID: 27904507
high-density lipoprotein cholesterol; cholesterol ester transfer protein; apolipoprotein AI; gene polymorphism
14.  Interaction between C-reactive protein and cognitive functions according to APOE gene polymorphism in post-menopausal women 
Archives of Medical Science : AMS  2016;12(6):1247-1255.
Introduction
A potential factor increasing the risk of the development of cognitive impairment with age is apolipoprotein E (APOE) ε4 carrier status. A subsequent factor which may increase the risk of development of cognitive impairment at an older age is the concentration of C-reactive protein (CRP). The objective of the study was to examine the relationship between cognitive functions and the concentration of CRP in post-menopausal women who were carriers of particular apolipoprotein E gene (APOE) polymorphisms.
Material and methods
A group of 402 women was recruited to the study. The inclusion criteria were: minimum two years after the last menstruation, follicle-stimulating hormone (FSH) concentration 30 U/ml, no dementi signs on Montreal Cognitive Assessment (MoCA). The computerized battery of the Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. APOE genotyping was performed by multiplex PCR. The blood plasma CRP levels were determined. Statistical analysis was performed using Statistica software.
Results
The level of neurocognitive index (NCI) and cognitive functions in post-menopausal women depends on apolipoprotein E gene polymorphism (p < 0.001) and the concentration of CRP (p < 0.05). A negative correlation was found between CRP and NCI (p = 0.018), and the reaction time (p = 0.008) of women with APOE ε2/ε3. A positive correlation was observed between CRP and visual memory (p = 0.025) in women with APOE ε3/ε3, and verbal memory (p = 0.023) in women with APOE ε3/ε4 or ε4/ε4.
Conclusions
Apolipoprotein E gene polymorphism may modify the relationship between CRP concentration and cognitive functions in post-menopausal women.
doi:10.5114/aoms.2016.62868
PMCID: PMC5108386  PMID: 27904515
menopause; cognition functions; apolipoprotein E gene polymorphisms; C-reactive protein
15.  Intraoperative diagnosis of sentinel lymph node metastases in breast cancer treatment with one-step nucleic acid amplification assay (OSNA) 
Archives of Medical Science : AMS  2016;12(6):1239-1246.
Introduction
The aim of the study was to evaluate the clinical usefulness of a one-step nucleic acid amplification assay (OSNA) for intraoperative detection of metastases to sentinel lymph nodes (SLNs) in comparison to examination of frozen sections, and to summarize the results of previous studies.
Material and methods
We enrolled 98 patients aged 58.13 ±10.74 years treated surgically for breast cancer, and 99 biopsies of SLNs were followed by analysis of 105 SLNs. The central 1 mm slice of SLN was used for examination of frozen sections, whereas 2 outer slices of SLNs were analyzed intraoperatively with OSNA. Detection of isolated tumor cells (ITC), micrometastases or macrometastases with OSNA extended surgery to axillary lymph node dissection. Congruency of results was assessed between OSNA and examination of frozen sections.
Results
One-step nucleic acid amplification assay detected metastases in 29/105 SLNs in surgery of 27/99 breasts, including ITC in 3/29 SLNs, micrometastases in 12/29 and macrometastases in 14/29. One-step nucleic acid amplification assay detected significantly more metastases to SLNs than examination of frozen sections (p < 0.0001). All 8 inconsistent results were positive in OSNA and negative in examination of frozen sections; ITC were identified in 2/8 SLNs and micrometastases in 6/8 SLNs. Sensitivity for OSNA was calculated as 100%, specificity as 90.47%, and κ was 79.16%.
Conclusions
One-step nucleic acid amplification assay analysis allows rapid and quantitative detection of mRNA CK19 with high specificity and a low rate of false positives. One-step nucleic acid amplification assay is a reliable tool for intraoperative diagnosis of whole SLNs during surgery of breast cancer. One-step nucleic acid amplification assay minimizes the need for secondary surgery and avoids delays in the adjuvant treatment.
doi:10.5114/aoms.2016.62902
PMCID: PMC5108387  PMID: 27904514
breast cancer; sentinel lymph node; intraoperative molecular study; cytokeratin 19
16.  The role of near-infrared spectroscopy in the detection of vulnerable atherosclerotic plaques 
Archives of Medical Science : AMS  2016;12(6):1308-1316.
Coronary artery disease is the leading cause of mortality worldwide. Most acute coronary syndromes are caused by a rupture of a vulnerable atherosclerotic plaque which can be characterized by a lipid-rich necrotic core with an overlying thin fibrous cap. Many vulnerable plaques can cause angiographically mild stenoses due to positive remodelling, which is why the extent of coronary artery disease may be seriously underestimated. In recent years, we have witnessed a paradigm shift in interventional cardiology. We no longer focus solely on the degree of stenosis; rather, we seek to determine the true extent of atherosclerotic disease. We seek to identify high-risk plaques for improvement in risk stratification of patients and prevention. Several imaging methods have been developed for this purpose. Intracoronary near-infrared spectroscopy is one of the most promising. Here, we discuss the possible applications of this diagnostic method and provide a comprehensive overview of the current knowledge.
doi:10.5114/aoms.2016.62904
PMCID: PMC5108388  PMID: 27904523
near-infrared spectroscopy; lipid-core plaque; vulnerable plaque
17.  Effects of hyperbaric oxygen therapy combined with platelet-rich plasma on diabetic wounds: an experimental rat model 
Archives of Medical Science : AMS  2016;12(6):1370-1376.
Introduction
Hyperbaric oxygen and platelet-rich plasma are used in the treatment of diabetic wounds. The aim of this study is to evaluate the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing diabetic wounds.
Material and methods
Thirty-six female Wistar albino rats were used in this study. Diabetes mellitus was induced chemically with an intraperitoneal injection of streptozotocin. The rats were divided into a control group, a hyperbaric oxygen group, a platelet-rich plasma group, and a combined therapy group. Platelet-rich plasma was applied just after the creation of the wound; hyperbaric oxygen treatment was carried out daily over 7 days. Wound healing was evaluated according to four parameters: ulcerations, epidermal thickness, density of dermal collagen fibers, and proliferation of dermal blood vessels.
Results
The number of active ulcers in the combined therapy group was fewer than in the control group (p = 0.039), and the wound area was greatest in controls (p < 0.001). The epidermal thickness in platelet-rich plasma and combined therapy groups was non-significantly greater than in the control group (p = 0.097 and p = 0.074, respectively). The amount of fibrous collagen in these two groups was greater than in the control group (p = 0.002).
Conclusions
Combined hyperbaric oxygen and platelet-rich plasma therapy was found to be successful in diabetic wound healing. The combination therapy had no additive effect in terms of angiogenesis and the development of new collagen fibers.
doi:10.5114/aoms.2016.62905
PMCID: PMC5108389  PMID: 27904531
hyperbaric oxygen; platelet-rich plasma; combination therapy
18.  Inducing apolipoprotein A-I synthesis to reduce cardiovascular risk: from ASSERT to SUSTAIN and beyond 
Archives of Medical Science : AMS  2016;12(6):1302-1307.
Increasing attention has focused on efforts to promote the biological activities of high-density lipoproteins (HDL) in order to reduce cardiovascular risk. Targeting apolipoprotein A-I (apoA-I), the major protein carried on HDL particles, represents an attractive approach to promoting HDL by virtue of its ability to increase endogenous synthesis of functional HDL particles. A number of pharmacological strategies that target apoA-I, including upregulation of its production with the bromodomain and extraterminal (BET) protein inhibitor RVX-208, development of short peptide sequences that mimic its action, and administration as a component of reconstituted HDL particles, have undergone clinical development. The impact of these approaches on cardiovascular biomarkers will be reviewed.
doi:10.5114/aoms.2016.62906
PMCID: PMC5108390  PMID: 27904522
apolipoprotein A-I; atherosclerosis; risk factors; clinical trials; lipids
19.  Serum pregnancy-associated plasma protein A levels in the first, second and third trimester of pregnancy: relation to newborn anthropometric parameters and maternal tobacco smoking 
Archives of Medical Science : AMS  2016;12(6):1256-1262.
Introduction
The purpose of this study was to evaluate the associations of the first, second and third trimester serum pregnancy-associated plasma protein A (PAPP-A) concentrations with neonatal anthropometric parameters. The effect of tobacco smoking during pregnancy on PAPP-A level was also studied.
Material and methods
One hundred and fifty healthy pregnant women were divided into smoking and tobacco-abstinent groups. Serum PAPP-A level was measured with the KRYPTOR rapid random-access immunoassay analyzer. The relationship between PAPP-A and newborn related outcome as well as markers of estimated intensity of cigarette smoking was evaluated by univariate and multivariate linear regression.
Results
Pregnancy-associated plasma protein A concentration was positively correlated with birth weight in the first (β = 31.6; p < 0.001), second (β = 10.6; p < 0.05), and third (β = 4.6; p < 0.001) trimester of gestation. A significant association between PAPP-A and birth body length and head circumference in the second (β = 0.02; p < 0.05) and third trimester (β = 0.01; p < 0.01) was also found. The serum PAPP-A levels were significantly lower in the smoking than in the tobacco-abstinent group in each trimester of pregnancy (p < 0.001). The largest impact of the number of cigarettes smoked per day on PAPP-A level was found in the second (β = –1.2; p = 0.004) and third trimester (β = –2.6; p = 0.001).
Conclusions
Maternal serum PAPP-A levels during gestation might be significant predictors for birth weight. Increased PAPP-A concentrations in the second and third trimester appeared to also be predictive for newborn body length and head circumference. Smoking alters maternal PAPP-A levels in all trimesters, with the greatest impact related to the number of cigarettes smoked per day.
doi:10.5114/aoms.2016.62908
PMCID: PMC5108391  PMID: 27904516
pregnancy-associated plasma protein A; tobacco smoking; pregnancy; birth weight; birth body length; head circumference
20.  Correlation between plasma angiopoietin-1, angiopoietin-2 and matrix metalloproteinase-2 in coronary heart disease 
Archives of Medical Science : AMS  2016;12(6):1214-1219.
Introduction
Angiopoietin-2 (Ang-2) plays a critical role in inducing tumor cell infiltration, and this invasive phenotype is caused by up-regulation of matrix metalloproteinase (MMP)-2. The relationship between Ang-2 and MMP-2 in atherosclerosis has not been reported yet. The aim is to measure the plasma concentrations of Ang-1, Ang-2 and MMP-2 and assess the correlation between the concentrations of these factors in coronary heart disease (CHD) patients.
Material and methods
The testing was done in a cross-sectional study. We prospectively enrolled 42 individuals with acute myocardial infarction, 42 individuals with unstable angina pectoris, 42 individuals with stable angina pectoris and 45 healthy control subjects. Concentrations of Ang-1, Ang-2 and MMP-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Spearman’s rank correlation was calculated to evaluate the relationships between MMP-2 and Ang-1, and MMP-2 and Ang-2 in patients with CHD.
Results
Patients with acute myocardial infarction and unstable angina pectoris had higher Ang-2 and MMP-2 levels compared with stable angina patients and healthy control subjects (p < 0.05), while concentrations of Ang-1 were not statistically different between the groups. Spearman’s rank correlation showed that Ang-2 levels positively correlated with MMP-2 in patients with CHD (r = 0.679, p < 0.001).
Conclusions
Plasma Ang-2 and MMP-2 levels but not Ang-1 levels were increased in patients with CHD. Ang-1 correlated weakly with MMP-2, whereas the Ang-2 and MMP-2 correlation was strong in patients with CHD. Ang-2 may play a role in atherosclerosis, and have an interaction with MMP-2.
doi:10.5114/aoms.2016.62909
PMCID: PMC5108392  PMID: 27904510
angiopoietin-1; angiopoietin-2; matrix metalloproteinase-2; coronary heart disease; correlation
21.  Correlation research between osteoporosis and left ventricular hypertrophy in older men 
Archives of Medical Science : AMS  2016;12(6):1220-1224.
Introduction
The aim of the study was to correlate between osteoporosis and left ventricular hypertrophy (LVH) in older men.
Material and methods
One hundred and forty-six cases of senile male subjects were selected and divided into a normal bone mineral density group, an osteopenia group, and an osteoporosis group based on bone mineral density (BMD). Detailed history inquiry and clinical examination were used to determine biochemical indicators. Femoral neck BMD and lumbar BMD were determined. Electrocardiography was performed to calculate the left ventricular mass index (LVMI). One-way analysis of variance and multiple linear regression analysis were performed.
Results
With the bone mass reduced, LVMI was gradually increased (p < 0.05), incidence of left ventricular hypertrophy was increased, and there were significant differences (p < 0.05). With LVMI as the dependent variable, multiple linear regression analysis showed that lumbar bone density, body mass index, age and serum creatinine were associated with LVMI independently (p < 0.05).
Conclusions
In patients with osteoporosis and osteopenia, LVH rates were much higher than in normal bone mineral density patients. Moreover, there might be a relationship between osteoporosis and LVH.
doi:10.5114/aoms.2016.62910
PMCID: PMC5108393  PMID: 27904511
osteoporosis; left ventricular hypertrophy; elderly men
22.  Exosomes as nanocarriers for siRNA delivery: paradigms and challenges 
Archives of Medical Science : AMS  2016;12(6):1324-1326.
Exosomes are nano-sized vesicles that facilitate intercellular communications through carrying genetic materials and functional biomolecules. Owing to their unique size and structure, exosomes have emerged as a useful tool to overcome the limitations of siRNA delivery. The use of exosomes as siRNA delivery vehicles lacks certain disadvantages of the existing foreign delivery systems such as viruses, polycationic polymers and liposomes, and introduces several advantages including inherent capacity to pass through biological barriers and escape from phagocytosis by the reticuloendothelial system, as well as being biocompatible, non-toxic, and immunologically inert. Different strategies have been employed to harness exosome-based delivery systems, including surface modification with targeting ligands, and using exosome-display technology, virus-modified exosomes, and exosome-mimetic vesicles. The present review provides a capsule summary of the recent advances and current challenges in the field of exosome-mediated siRNA delivery.
doi:10.5114/aoms.2016.62911
PMCID: PMC5108394  PMID: 27904525
exosome; siRNA; microRNA; nanomedicine; drug delivery; gene therapy
23.  A diagnostic one-step real-time reverse transcription polymerase chain reaction method for accurate detection of influenza virus type A 
Archives of Medical Science : AMS  2016;12(6):1286-1292.
Introduction
Influenza A is known as a public health concern worldwide. In this study, a novel one-step real-time reverse transcription polymerase chain reaction (rtRT-PCR) assay was designed and optimized for the detection of influenza A viruses.
Material and methods
The primers and probe were designed based on the analysis of 90 matrix nucleotide sequence data of influenza type A subtypes from the GenBank database of the National Center for Biotechnology Information (NCBI). The influenza virus A/Tehran/5652/2010 (H1N1 pdm09) was used as a reference. The rtRT-PCR assay was optimized, compared with that of the World Health Organization (WHO), and its analytical sensitivity, specificity and reproducibility were evaluated. In total, 64 nasopharyngeal swabs from patients with influenza-like illness (ILI) and 41 samples without ILI symptoms were tested for the virus, using conventional cell culture, direct immunofluorescence antibody (DFA) methods, and one-step rtRT-PCR with the designed primer set and probe and the WHO’s.
Results
The optimized assay results were similar to the WHO’s. The optimized assay results were similar to WHO’s, with non-significant differences for 10–103 copies of viral RNA/reaction (p > 0.05). It detected 10 copies of viral RNA/reaction with high reproducibility and no cross reactivity with other respiratory viruses. A specific cytopathic effect was observed in 6/64 (9.37%) of the ILI group using conventional culture and DFA staining methods; however, it was not seen in non-ILI. Also, the results of our assay and the WHO’s were similar to those of viral isolation and DFA staining.
Conclusions
Given the high specificity, sensitivity and reproducibility of this novel assay, it can serve as a reliable diagnostic tool for the detection of influenza A viruses in clinical specimens and lab experiments.
doi:10.5114/aoms.2016.62914
PMCID: PMC5108395  PMID: 27904520
influenza A virus; one-step real-time polymerase chain reaction; detection
24.  What should the target blood pressure goals be? 
Archives of Medical Science : AMS  2016;12(6):1377-1380.
doi:10.5114/aoms.2016.62916
PMCID: PMC5108396  PMID: 27904532

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