Górnośląskie Centrum Medyczne

BACKGROUND: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. METHODS: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. RESULTS: Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). CONCLUSIONS: Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Aims: To investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease. Methods and results: The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39-0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11-0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37-0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27-1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10-4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07-0.97, P = 0.045). Conclusion: At one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted. ClinicalTrials.gov Identifier: NCT02015832.

Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin. Biosynthesis of melanins takes place in melanosomes, which are specialized cytoplasmic organelles of melanocytes - dendritic cells located in the basal layer of the epidermis, uveal tract of the eye, hair follicles, as well as in the inner ear, central nervous system and heart. Melanogenesis is a multistep process and begins with the conversion of amino acid L-tyrosine to DOPAquinone. The addition of cysteine or glutathione to DOPAquinone leads to the intermediates formation, followed by subsequent transformations and polymerization to the final product, pheomelanin. In the absence of thiol compounds DOPAquinone undergoes an intramolecular cyclization and oxidation to form DOPAchrome, which is then converted to 5,6-dihydroksyindole (DHI) or 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Eumelanin is formed by polymerization of DHI and DHICA and their quinones. Regulation of melanogenesis is achieved by physical and biochemical factors. The article presents the intracellular signaling pathways: cAMP/PKA/CREB/MITF cascade, MAP kinases cascade, PLC/DAG/PKCβ cascade and NO/cGMP/PKG cascade, which are involved in the regulation of expression and activity of the melanogenesis-related proteins by ultraviolet radiation and endogenous agents (cytokines, hormones). Activity of the key melanogenic enzyme, tyrosinase, is also affected by pH and temperature. Many pharmacologically active substances are able to inhibit or stimulate melanin biosynthesis, as evidenced by in vitro studies on cultured pigment cells.

The use of growth factors in combination with tissue engineering seems to be the most promising method in the future for the treatment of tissue, bone and cartilage defect. Growth factors are cytokines with regulatory functions for healing in tissues of the musculoskeletal system. These small peptides are synthesised by resident cells at the site of injury such as mesenchymal stem cells and chondrocytes, or by the infiltrating inflammatory process. Platelet-rich plasma (PRP) is a novel osteoinductive therapeutic approach that is increasingly used in treatment of such complications of bone healing processes. The activator for PRP is a mixture of thrombin and calcium chloride. After connecting these substances platelet-rich gel (PRG) is formed and numerous regulatory molecules to the injury site such as PDGF, TGF-, VEGF, IGF, EGF and antimicrobial proteins are released. The aim of this article is presentation of present knowledge about properties and possibilities of using platelet-rich plasma in the treatment of soft tissue and bone healing disturbances.

BACKGROUND:\n\nIn models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.\nOBJECTIVES:\n\nTo investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.\nMETHODS:\n\nInnate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.\nRESULTS:\n\nIn bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.\nCONCLUSIONS:\nIncreased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.

AIMS: The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial. METHODS AND RESULTS: SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35). CONCLUSIONS: Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.

PURPOSE: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naive patients with neovascular age-related macular degeneration enrolled in LUMINOUS study. METHODS: This 5-year, prospective, multicenter, observational study recruited 30,138 adult patients (treatment-naive or previously treated with ranibizumab or other ocular treatments) who were treated according to the local ranibizumab label. RESULTS: Six thousand two hundred and forty-one treatment-naive neovascular age-related macular degeneration patients were recruited. Baseline (BL) demographics were, mean (SD) age 75.0 (10.2) years, 54.9% females, and 66.5% Caucasian. The mean (SD) visual acuity (VA; letters) gain at 1 year was 3.1 (16.51) (n = 3,379; BLVA, 51.9 letters [Snellen: 20/92]) with a mean (SD) of 5.0 (2.7) injections and 8.8 (3.3) monitoring visits. Presented by injection frequencies <3 (n = 537), 3 to 6 (n = 1,924), and >6 (n = 918), visual acuity gains were 1.6 (14.93), 3.3 (16.57), and 3.7 (17.21) letters, respectively. Stratified by BLVA <23 (n = 382), 23 to <39 (n = 559), 39 to <60 (n = 929), 60 to <74 (n = 994), and ≥74 (n = 515), visual acuity change was 12.6 (20.63), 6.7 (17.88), 3.6 (16.41), 0.3 (13.83), and -3.0 (11.82) letters, respectively. The incidence of ocular/nonocular adverse events was 8.2%/12.8% and serious adverse events were 0.9%/7.4%, respectively. CONCLUSION: These results demonstrate the effectiveness and safety of ranibizumab in treatment-naive neovascular age-related macular degeneration patients.

AIM: The aim of the study was the validation and adaptation of the ORTO-15 Questionnaire in the group of the Polish schoolgirls and schoolboys. METHODS: The study included 399 participants (15-21 years old), all of them high school students in the city of Sosnowiec. The ORTO-15 is a tool created in Italy by L.M. Donini, comprising of 15 items describing intensification of orthorexia risk (population diagnosis). The validation procedure incorporated three basic methods to be applied in the reliability analysis - the comparison of double tests with the same method, the statistical properties analysis of test items as well as analysis of the relation of test items with the general test result. Moreover, the compliance of the ORTO-15 Questionnaire results with other questionnaire focused on eating habits (EAT-26) was studied. RESULTS: The reliability analysis of the ORTO-15 Questionnaire based on repeatability of the responses presents a very good (kappa: 0.81 - 1.00 for 5 items) and a good repeatability (kappa: 0.61 - 0.80 for 10 items). The reliability analysis based on the value of the Cronbach's α reached a satisfactory level (0.7 - 0.9). A full agreement of in the occurrence of orthorexia risk and the risk of eating disorders concerned 47.2% (Kappa = 0.04; 95% CI: 0.004 - 0.09) for the Ortho-40 and 88.2% (Kappa = 0.32; 95% CI: 0.17 - 0.47) for the Ortho-35. CONCLUSIONS: The ORTO-15 questionnaire is a reliable tool to identify the risk of ON in population studies in the group of urban youth aged 15 - 21.

Girls and women with autism are often undiagnosed, misdiagnosed or receive a diagnosis of autism at later age. This can result in adverse outcomes in their well-being, mental health, education, employment, and independence. The diagnosis of autism spectrum condition/disorder (hereinafter referred to as autism), with its current features linked with descriptions in the major diagnostic classification systems, is based primarily on observations and research on males. The term 'Autism Spectrum Condition' (ASC), used in this paper, has been coined by Simon Baron-Cohen and used in the professional literature for a decade to respect these individuals on the autism spectrum who feel that the term 'disorder'is stigmatizing, whereas ASC presents both the strengths of these people and difficulties they experience. The research shows that autism in females has unique symptomatology and manifests itself differently, more subtly, especially in high-functioning girls and women, i.e., those with fluent speech, average or above-average intelligence quotient. The research also shows diagnostic stereotypes and lack of required sensitivity to identify autistic females. Additionally they do not reflect the unique presentation of autism in females demonstrated by greater compensatory capacity and an ability to develop sophisticated methods of 'camouflaging'and masquerading. Furthermore, autism in females is associated with high comorbidity during adolescence including anxiety disorder, tic disorder, depression, high incidence of suicide, eating disorders, and high rates of other medical problems. Timely diagnosis, however, can reduce the difficulties that females with autism experience over their lifetime, allowing for the assessment of their needs regarding health, education, leisure, social relationships, and employment.

Background: Frailty has emerged as a key medical syndrome predictive of comorbidity, disability, institutionalization and death. As a component of the five frailty phenotype diagnostic criteria, patient grip strength deserves attention as a simple and objective measure of the frailty syndrome. The aim of this study was to assess conditions that influence grip strength in geriatric inpatients. Patients and methods: The study group consisted of 80 patients aged 78.6±7.0 years ( X ± SD), with 68.8% women, admitted to the Department of Geriatrics. A comprehensive geriatric assessment was complemented with assessment for the frailty phenotype as described by Fried et al for all patients in the study group. Functional assessment included Barthel Index of Activities of Daily Living (Barthel Index), Instrumental Activities of Daily Living Scale and Mini-Mental State Examination. Results: Three or more frailty criteria were positive in 32 patients (40%), while 56 subjects (70%) fulfilled the frailty criterion of weakness (grip strength test). Multivariate linear regression analysis revealed that two independent measures showed positive association with grip strength – Mini-Mental State Examination score (β=0.239; P =0.001) and statin use (β=0.213; P =0.002) – and four independent measures were negatively associated with grip strength – female sex (β=–0.671; P <0.001), C-reactive protein (β=–0.253; P <0.001), prior myocardial infarction (β=–0.190; P =0.006) and use of an antidepressant (β=–0.163; P =0.018). Low physical activity was identified as the only independent qualitative frailty component associated with 2-year mortality in multivariate logistic regression analysis after adjustment for age and sex (odds ratio =6.000; 95% CI =1.357–26.536; P =0.018). Conclusion: Cognitive function, somatic comorbidity and medical treatment affect grip strength as a measure of physical frailty in geriatric inpatients. Grip strength was not predictive of 2-year mortality in this group. Keywords: frailty, cognitive function, statin, antidepressant, physical activity, mortality

Background: Inpatient geriatric falls are a frequent complication of hospital care that results in significant morbidity and mortality. Objective: Evaluate factors associated with falls in geriatric inpatients after implementation of the fall prevention program. Methods: Prospective observational study comprised of 788 consecutive patients aged 79.5±7.6 years ( x̅ ± standard deviation) (66% women and 34% men) admitted to the subacute geriatric ward. Comprehensive geriatric assessment (including Mini-Mental State Examination, Barthel Index of Activities of Daily Living, and modified Get-up and Go Test) was performed. Confusion Assessment Method was used for diagnosis of delirium. Patients were categorized into low, moderate, or high fall risk groups after clinical and functional assessment. Results: About 15.9%, 21.1%, and 63.1% of participants were classified into low, moderate, and high fall risk groups, respectively. Twenty-seven falls were recorded in 26 patients. Increased fall probability was associated with age ≥76 years ( P <0.001), body mass index (BMI) <23.5 ( P =0.007), Mini-Mental State Examination <20 ( P =0.004), Barthel Index <65 ( P =0.002), hemoglobin <7.69 mmol/L ( P =0.017), serum protein <70 g/L ( P =0.008), albumin <32 g/L ( P =0.001), and calcium level <2.27 mmol/L. Four independent factors associated with fall risk were included in the multivariate logistic regression model: delirium (odds ratio [OR] =7.33; 95% confidence interval [95% CI] =2.76–19.49; P <0.001), history of falls (OR =2.55; 95% CI =1.05–6.19; P =0.039), age (OR =1.14; 95% CI =1.05–1.23; P =0.001), and BMI (OR =0.91; 95% CI =0.83–0.99; P =0.034). Conclusion: Delirium, history of falls, and advanced age seem to be the primary risk factors for geriatric falls in the context of a hospital fall prevention program. Higher BMI appears to be associated with protection against inpatient geriatric falls. Keywords: falls, geriatric inpatients, comprehensive geriatric assessment, delirium, body mass index

BACKGROUND AND OBJECTIVES: Masitinib is a selective tyrosine kinase inhibitor, targeting innate immune cells (mast cells and microglia) that are involved in the pathophysiology of progressive multiple sclerosis (MS). Study AB07002 assessed oral masitinib in patients with progressive MS who were progressing but not clinically active. METHODS: This randomized, double-blind, 2 parallel-group, placebo-controlled trial assessing 2 dose levels of masitinib vs equivalent placebo was conducted at 116 hospital clinics and specialized MS centers in 20 countries. Randomization (2:1) with minimization was performed centrally using an automated system. Patients, physicians, and outcome assessors remained masked to treatment group allocation. Patients with primary progressive MS (PPMS) or nonactive secondary progressive MS (nSPMS) without relapse for ≥2 years, aged 18-75 years, with baseline Expanded Disability Status Scale (EDSS) 2.0-6.0, and regardless of time from onset were treated for 96 weeks. The primary end point was overall EDSS change from baseline using repeated measures (generalized estimating equation, timeframe W12-W96, measured every 12 weeks), with positive values indicating increased clinical deterioration. Efficacy and safety were assessed in all randomly assigned and treated patients. RESULTS: = 0.0256. Safety was consistent with masitinib's known profile (diarrhea, nausea, rash, and hematologic events), with no elevated risk of infection. Efficacy results from the independent uptitrated masitinib 6.0 mg/kg/d parallel group were inconclusive, and no new safety signal was observed. DISCUSSION: Masitinib (4.5 mg/kg/d) can benefit people with PPMS and nSPMS. A confirmatory phase 3 study will be initiated to substantiate these data. TRIAL REGISTRATION INFORMATION: The first participant was randomized to study AB07002 on August 25, 2011. The trial was registered with the European Clinical Trials Database (#EudraCT 2010-021219-17) on July 1, 2011 (clinicaltrialsregister.eu/ctr-search/trial/2010-021219-17/ES) and with ClinicalTrials.gov (#NCT01433497) on September 14, 2011 (clinicaltrials.gov/ct2/show/NCT01433497). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that masitinib 4.5 mg/kg/d decreased progression of disability, measured by the EDSS, in adults with PPMS or patients with nSPMS (with no exacerbations in the last 2 years).

The aetiopathogenesis of fatigue in multiple sclerosis (MS) is not clear. It could be associated with structural changes of the central nervous system, but also with mood and sleep disorders. The purpose of the study was to evaluate frequency of fatigue and its association with sleep and mood disorders in MS patients. The examined group consisted of 122 MS patients (mean age 37.7 ± 10.8 years). The following questionnaires were used: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), Montgomery-Asberg Depression Rating Scale (MADRS), and Hospital Anxiety and Depression Scale (HADS). Fatigue was present in 75 MS patients (61.5%). Excessive daytime sleepiness was observed in 25 (20.5%), insomnia in 73 patients (59.8%). According to MADRS, depressive symptoms were present in 33 (27%), according to HADS in 15 people (12.3%). Anxiety was present in 32 patients (26.2%). We observed an association between fatigue (FSS) and sleep disorders (ESS, AIS) and also between fatigue and either depression (MADRS, HADS-D) or anxiety (HADS-A). The FSS score was not associated with age, sex, disease course and duration, Expanded Disability Status Stage (EDSS), treatment or level of education in MS patients. In inactive professionally people we noted significantly higher FSS scores (44.8 ± 13.8) in comparison with active individuals (37.2 ± 14.9; p = 0.0053). Fatigue is a very common symptom in MS, sometimes associated with sleep disorders, depressive symptoms or anxiety. The treatable causes of fatigue in MS such as sleep and mood disturbances should be identified and treated. Etiopatogeneza zmęczenia w stwardnieniu rozsianym (SR) jest niejasna. Może mieć związek ze zmianami strukturalnymi w obrębie ośrodkowego układu nerwowego, jak również z zaburzeniami snu i nastroju. Celem pracy była ocena częstości występowania zmęczenia u chorych na SR oraz analiza zależności ze współwystępującymi zaburzeniami snu i nastroju. W badaniu wzięło udział 122 chorych na SR (średnia wieku: 37,7 ± 10,8 roku). Badanie przeprowadzono za pomocą następujących kwestionariuszy: Skali Stopnia Zmęczenia (Fatigue Severity Scale – FSS), Skali Senności Epworth (Epworth Sleepiness Scale – ESS), Ateńskiej Skali Bezsenności (Athens Insomnia Scale – AIS), Skali Depresji Montgomery-Asberg (Montgomery-Asberg Depression Rating Scale – MADRS) oraz Skali Lęku i Depresji wg Zigmonda i Snaitha (Hospital Anxiety and Depression Scale – HADS). Zmęczenie stwierdzono u 75 chorych na SR (61,5%). U 25 osób (20,5%) rozpoznano nadmierną senność w ciągu dnia, u 73 osób (59,8%) bezsenność. Według MADRS, objawy depresyjne występowały u 33 (27%), wg HADS u 15 (12,3%) osób. Objawy lękowe były obecne u 32 chorych (26,2%). Zaobserwowano korelację pomiędzy występowaniem zmęczenia (FSS) a zaburzeniami snu (ESS, AIS), objawami depresyjnymi (MADRS, HADS-D) i lękowymi (HADS-A). Nie stwierdzono zależności pomiędzy wynikiem FSS a wiekiem, płcią, przebiegiem i czasem trwania choroby, EDSS, sposobem leczenia ani poziomem wykształcenia. Osoby nieaktywne zawodowo uzyskały znamiennie wyższy wynik w kwestionariuszu FSS (44,8 ± 13,8) w porównaniu z osobami pracującymi zawodowo (37,2 ± 14,9; p = 0,0053). Zmęczenie jest częstym objawem występującym u chorych na SR, może towarzyszyć zaburzeniom snu, objawom depresyjnym i lękowym. Przyczyny zmęczenia poddające się terapii (zaburzenia snu i nastroju) powinny być rozpoznane i leczone.

INTRODUCTION Lowering exposure to dyslipidemias is one of the biggest challenges in cardiovascular disease prevention. OBJECTIVES The aim of the study was to describe the prevalence of dyslipidemias and treatment of hypercholesterolemia in Poland, and to assess changes since the period of 2003-2005. PATIENTS AND METHODS Two cross-sectional surveys of the random samples of the Polish population were performed in the years 2003-2005 (WOBASZ) and 2013-2014 (WOBASZ II). Interviews were carried out according to a standard questionnaire. Blood lipid levels were determined in a single laboratory in frozen samples using the enzymatic colorimetric method. RESULTS The analysis included 14151 participants aged 20-74 years (WOBASZ) and 5947 participants aged 20-99 years (WOBASZ II). In the 2013-2014 survey, hypercholesterolemia was found in 70.3% of men and 64.3% of women. Isolated hypertriglyceridemia was found in 5.6% of men and 2.4% of women. Isolated low levels of high-density lipoprotein cholesterol (HDL-C) were found in 5.1% of men and in 7.3% of women. The prevalence of hypercholesterolemia did not change significantly with regards to the 2003-2005 survey. An increase in the prevalence of hypertriglyceridemia was found in men (relative ratio [RR], 1.26; 95% confidence interval [CI], 1.03-1.55), and an increase in the prevalence of low HDL-C levels was observed in both sexes (men: RR, 2.26; 95% CI, 1.77-2.88; women: RR, 1.94; 95% CI, 1.61-2.33). There was an increase in the proportion of persons receiving high- or moderate-intensity statin therapy. However, 60,6% of persons with hypercholesterolemia were not aware of their condition, and only 6% were treated and achieved the treatment target. CONCLUSIONS There is an urgent need for more effective strategies for the prevention and management of dyslipidemias.

Fatty acids (FAs) are components of cell membrane, enzymes, and hormones and are one of the most important energy sources for many organisms. There are several types of fatty-acid oxidative degradation processes in the cell, namely alpha-, beta-, and omega-oxidation, which take place in specialized cellular structures: mitochondria and peroxisomes. The best-known pathway is beta-oxidation taking place in the matrix of mitochondria. It is responsible for the degradation of straight-chain FAs. The pathway of beta-oxidation of fatty acids is comprised of at least 25 enzymes and specific transport proteins. Deficiencies in 18 of them have been demonstrated to cause disease in humans. These diseases show a wide variety of symptoms, which can be expressed at random, one at a time, or in sets, characteristic of the individual rather than the metabolic character of the disease. Disorders of beta-oxidation are believed to cause about 1-3% of unexplained sudden infant deaths (SIDS). Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), which have significant neonatal and maternal morbidity and mortality, have also been associated with beta-oxidation deficiency in fetuses. This review summarizes recent observations on disorders associated with fatty-acid oxidation: deficiencies of beta-oxidation enzymes, namely VLCAD, TFP and LCHAD, MCAD, MCKAT, M/SCHAD, and SCAD, and deficiencies of the enzymes TCP I, CT, and CPT II of the carnitine cycle.

Cognitive dysfunctions are part of the symptomatology of depressive disorders but they may persist even after the patient reaches symptomatic remission. As persistent symptoms of depression, cognitive dysfunctions may inhibit and restrict the patient's functioning in many spheres and significantly impair its quality. In addition, they increase the risk of somatic diseases and contribute to the increase of benefits disbursed from state aid. Furthermore, it is a factor negatively affecting the prognosis of depressive disorders because it increases the risk of recurrence of depression and reduces the susceptibility to pharmacotherapy. Neural network dysfunctions and changes in morphometry in particular areas of the brain are responsible for the persistence of cognitive deficits after MDD treatment. Most of currently used thymoleptics facilitate remission of depressive disorders but do not lead to reversal of cognitive deficits. There is growing evidence that antidepressants used in clinical practice can improve cognitive functions regardless of their impact on the affective component. The aim of the present study is to discuss the neurobiological mechanisms of cognitive dysfunctions and their clinical symptoms, and to present therapeutic prospects for patients with persistent cognitive dysfunctions in depressive disorders.

The article presents the melanogenesis pathway and the role of cyclic adenosine monophosphate (cAMP) and microphthalmia transcription factor (MITF) in regulation of this process. Products of melanogenesis are eu- and/or pheomelanins synthesized in a multistage process of tyrosine oxidation and polymerization. The conversions require the presence of tyrosinase (TYR, key enzyme), tyrosine hydroxylase isoform I (THI) and tyrosinase related proteins (TRP1 and TRP2). Many types of signal molecules and transcription factors participate in regulation of melanin synthesis, but the most important are cAMP and MITF. cAMP is the second messenger in the intracellular signal cascade, which is synthesized from adenosine triphosphate (ATP) by adenylyl cyclase, activated among others by the melanocortin receptor and the αS subunit of G protein. The signal molecule cAMP regulates MITF, TYR, THI, GTP-cyclohydroxylase I (GTP-CHI) transcription and phenylalanine hydroxylase (PAH) phosphorylation at Ser16 by protein kinase A (PKA). Mutations of genes encoding proteins belonging to the cAMP signal cascade may lead to McCune-Albright and Carney syndromes. MITF is one of the most important nuclear transcription factors regulating melanogenesis. Currently 10 isoforms of human MITF are known, but in melanocytes only MITF-M, MITF-Mdel, MITF-A and MITF-H occur. MITF transcription factor regulates melanogenesis by activation of tyrosinase, TRP1 and TRP2 transcription. It also affects expression of other factors regulating melanosome maturation, biogenesis and transport. Moreover, it regulates melanocyte proliferation and protection against apoptosis. Mutations of the MITF gene may lead to hereditary diseases: Waardenburg type II and Tietz syndromes.

OBJECTIVES: The following article presents the relationship between vegetarianism and orthorexia nervosa (ON). Vegetarianism is an ideology and a way of life that aims at minimizing animal exploitation. A vegetarian diet excludes the consumption of meat together with other animal derived products. According to scientists, orthorexia nervosa is considered to be a new, yet unclassified eating disorder. It involves introducing dietary restrictions by individuals who feel a desire to improve their health status by healthy eating. METHODS: The study involved 2,611 participants, namely 1,346 vegetarians and 1,265 non-vegetarians. The research questionnaire consisted of general personal and anthropometric characteristics, the BOT(Bratman Test for Orthorexia) and questions evaluating the participants' attitude towards nutrition. RESULTS: Based on the obtained results, health food fanaticism is more specific to vegetarians than non-vegetarians. The risk for orthorexia nervosa decreases with age and diet duration. The biggest number of health food fanatics was found in the group of lacto-vegetarians, a lower number among ovo-vegetarians and lacto-ovo-vegetarians, and the smallest number was observed in the vegan group. Also, vegetarians were reported to have dietary consultations as frequently as non-vegetarians. CONCLUSIONS: Very few studies can be found on the relationship between orthorexia nervosa and vegetarianism. Some scientists believe that vegetarians are particularly prone to orthorexia nervosa. In addition, it has been suggested by other researchers that vegetarianism can be used to mask eating disorders, as it allows these affected individuals to avoid certain products or situations related to food. The direction of cause and effect cannot be determined.

Inflammation is a central feature of stable chronic obstructive pulmonary disease (COPD) and involves both activation of structural cells of the airways and the lungs and the activation and/or recruitment of infiltrating inflammatory cells. This results in enhanced expression of many pro-inflammatory proteins and reduced expression of some anti-inflammatory mediators. An altered protein expression is generally associated with concomitant changes in gene expression profiles in a cell-specific manner. Increased understanding of the role of transcription factors and of the signaling pathways leading to their activation in stable COPD will provide new targets to enable the development of potential anti-inflammatory drugs. Several new compounds targeting these pathways and/or transcription factors are now in development for the treatment of stable COPD. Furthermore, glucocorticoids drugs already in clinical use act through their own transcription factor, the glucocorticoid receptor, to control the expression of inflammatory and anti-inflammatory genes.

INTRODUCTION: The identification of patients with essential thrombocythemia (ET) who are at increased risk of acquired von Willebrand syndrome (AVWS) would likely facilitate individualization of treatment and improve its outcomes. OBJECTIVES: The aim of the study was to determine the prevalence of AVWS in patients with ET and to verify whether individuals with and without this bleeding disorder differ in terms of their baseline clinical parameters. PATIENTS AND METHODS: The study included 170 consecutive patients with ET. AVWS was diagnosed on the basis of reduced levels of von Willebrand factor and abnormal results of other routine tests. Patients with and without concomitant AVWS were compared in terms of their demographic characteristics, past and current medical histories, and laboratory parameters. RESULTS: Concomitant AVWS was found in 34 patients (20%). Individuals with AVWS were diagnosed with ET at a significantly younger age than those without the syndrome. In addition, these patients significantly less often were in remission at the time of testing, had significantly higher erythrocyte and platelet counts, and showed abnormalities of the coagulation profile corresponding to defects of primary hemostasis as well as abnormal values of most parameters used i n the routine diagnosis of AVWS. CONCLUSIONS: Even every fifth patient with ET may develop AVWS. Young age at diagnosis of ET and the lack of response to its previous treatment are potential risk factors for AVWS that should be considered during the management of the primary condition. All patients with ET and signs of a bleeding disorder, irrespective of the platelet count, should be tested for the presence of AVWS.