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Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER.Adults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)-5, IL-13, periostin, thymus and activation-regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels.Positive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL-5, IL-13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55-83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL-5, IL-13, periostin, TARC, or TSLP, when these biomarkers were assessed individually.At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.

Background Patients with severe, uncontrolled asthma experience frequent exacerbations and hospitalization, leading to poor health-related quality of life. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo. Objective This analysis further assessed the impact of tezepelumab on patient-reported outcomes (PROs) in PATHWAY. Methods Adults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. PROs were assessed using the asthma control questionnaire–6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of ≥0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity. Results Overall, 550 patients were randomized. Up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity. Conclusion Tezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma.We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078.Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per μL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per μL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group.We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per μL.AstraZeneca and Amgen.

Objectives: The coarctation of aorta is commonly related to bicuspid aortic valve. The aim of the study was to assess arterial stiffness in adults after aortic coarctation repair and to eva...

Introduction and Objectives Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP), an epithelial cytokine implicated in asthma pathogenesis. In the PATHWAY study (NCT02054130), tezepelumab consistently reduced annualized asthma exacerbation rates (AAER) versus placebo in adults with severe uncontrolled asthma, irrespective of baseline disease characteristics. This analysis evaluated the efficacy of tezepelumab by baseline body mass index (BMI). Methods Patients aged 18–75 years with severe, uncontrolled asthma were randomized to receive subcutaneous tezepelumab (70 mg every 4 weeks [Q4W], 210 mg Q4W, 280 mg every 2 weeks) or placebo, for 52 weeks. AAER was estimated for baseline BMI subgroups of Results Overall, 550 patients were randomized. Lower BMI was associated with younger age, higher baseline blood eosinophil counts and higher fractional exhaled nitric oxide levels. Among placebo recipients, AAER over 52 weeks was similar by BMI subgroup (0.70–0.76 exacerbations per person-year). AAER over 52 weeks was reduced by 79% (95% CI: 57–89), 70% (95% CI: 41–85) and 50% (95% CI: 6–73) for pooled tezepelumab groups versus placebo in patients with a BMI of Conclusions Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma irrespective of baseline BMI, providing further evidence that tezepelumab can meaningfully reduce exacerbations in a broad population of patients with severe asthma.

Introduction and Objectives In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced annualized asthma exacerbation rates (AAER) by up to 71% versus placebo in adults with severe, uncontrolled asthma. We evaluated the effect of tezepelumab on exacerbations in patients from PATHWAY with low and high bronchodilator reversibility. Methods Adults with severe, uncontrolled asthma were randomized to receive tezepelumab (70 mg every 4 weeks [Q4W], 210 mg Q4W or 280 mg every 2 weeks) or placebo for 52 weeks. AAER and the rate of exacerbations resulting in hospitalization or emergency room (ER) visits were estimated for patients with low ( Results Of 550 randomized patients, 299 and 251 had low and high FEV1 reversibility, respectively. Tezepelumab 210 mg (phase 3 dose) reduced AAER over 52 weeks by 70% (95% confidence interval [CI]: 41, 85) and 72% (95% CI: 32, 88) versus placebo in patients with low and high FEV1 reversibility, respectively. For pooled tezepelumab doses, AAER was reduced by 69% (95% CI: 50, 81) and 60% (95% CI: 26, 78) in the low and high groups, respectively. Data were similar for 70 and 280 mg. Exacerbations resulting in hospitalizations or ER visits were reduced by 85% (95% CI: 21, 97) and 78% (95% CI: −32, 96) versus placebo in patients with low and high FEV1 reversibility, respectively, for tezepelumab 210 mg, and by 84% (95% CI: 51, 94) and 64% (95% CI: −18, 89) in the pooled tezepelumab group, respectively. Conclusions Tezepelumab treatment reduced AAER irrespective of baseline bronchodilator reversibility, further supporting its potential benefits in a broad population of patients with severe asthma.

Background: In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced annualized asthma exacerbation rates (AAER) by up to 71% versus placebo in adults with severe, uncontrolled asthma. We evaluated the effect of tezepelumab on exacerbations in patients from PATHWAY with low and high bronchodilator reversibility. Methods: Adults with severe, uncontrolled asthma were randomized to receive tezepelumab (70mg every 4 weeks [Q4W], 210mg Q4W or 280mg every 2 weeks) or placebo for 52 weeks. AAER and the rate of exacerbations resulting in hospitalization or emergency room (ER) visits were estimated for patients with low ( Results: Of 550 randomized patients, 299 and 251 had low and high FEV1 reversibility, respectively. Tezepelumab 210mg (phase 3 dose) reduced AAER over 52 weeks by 70% (95% confidence interval [CI]: 41, 85) and 72% (95% CI: 32, 88) versus placebo in patients with low and high FEV1 reversibility, respectively. For pooled tezepelumab doses, AAER was reduced by 69% (95% CI: 50, 81) and 60% (95% CI: 26, 78) in the low and high groups, respectively. Data were similar for 70 and 280mg. Exacerbations resulting in hospitalizations or ER visits were reduced by 85% (95% CI: 21, 97) and 78% (95% CI: −32, 96) versus placebo in patients with low and high FEV1 reversibility, respectively, for tezepelumab 210mg, and by 84% (95% CI: 51, 94) and 64% (95% CI: −18, 89) in the pooled tezepelumab group, respectively. Conclusions: Tezepelumab treatment reduced AAER irrespective of baseline bronchodilator reversibility, further supporting its potential benefits in a broad population of patients with severe asthma.

Polish women have not been studied in regard to fear, likelihood, or confidence about dangerous situations, nor has there been an instrument to measure those perceptions. The purpose of the study was fourfold: first, to present the Polish translation and validation of the Perception of Dangerous Situations Scale (PDSS-P) and second, to assess Polish women’s perceived fear, likelihood, and confidence about dangerous situations using the PDSS-P (41 items). The third purpose was to determine to what degree the General Self-Efficacy Scale (GSES) and/or the Hope for Success Scale (KNS) correlated with any of the three subscales of the PDSS-P. The fourth purpose was to determine the congruence of the PDSS-P to the original PDSS. Two other tools (GSES and KNS) were administered to determine concurrent validity with the PDSS. A sample of 208 women aged 19 to 27 years ( M = 21.04, SD = 1.88) participated in the study. Five factors were determined for each subscale, similar to the original version of the PDSS. Women reported they were more afraid of being raped by a stranger than being murdered. Their estimation of the likelihood of some serious events occurring was not congruent with statistical realities. The women thought the least likely events to happen to them in the next year would be being raped or beaten by someone they know, or being held prisoner by someone who wanted to murder them. Confidence to manage dangerous situations was low in cases of being raped by strangers or known people, being kidnapped, or being attacked. The GSES and KNS provided useful information, in that they did not measure the same constructs as the PDSS-P.

Background Tezepelumab is an anti–thymic stromal lymphopoietin mAb. In the PATHWAY phase IIb study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. Objective This post hoc analysis assessed the efficacy of tezepelumab in PATHWAY participants with perennial allergy. Methods Adults (N = 550) with severe, uncontrolled asthma were randomized to receive tezepelumab (70 mg or 210 mg every 4 weeks or 280 mg every 2 weeks) or placebo, for 52 weeks. The AAER over 52 weeks was analyzed in patients grouped by sensitivity to perennial aeroallergens and by eligibility for omalizumab treatment according to the US or European Union prescribing information. Change from baseline to week 52 in prebronchodilator FEV1 and type 2 biomarkers was assessed in the perennial allergy subgroups. Results Across doses, tezepelumab reduced the AAER versus placebo by 66% to 78% in patients with perennial allergy (n = 254) and 67% to 71% in patients without perennial allergy (n = 261). Tezepelumab improved prebronchodilator FEV1 and reduced blood eosinophil counts and fractional exhaled nitric oxide levels over 52 weeks, irrespective of perennial allergy status. Tezepelumab reduced the AAER versus placebo by 61% to 82% in omalizumab-eligible patients (US, n = 159; European Union, n = 101) and 63% to 70% in omalizumab-ineligible patients (US, n = 372; European Union, n = 440), respectively. Conclusions Treatment with tezepelumab reduced exacerbations, improved lung function, and reduced type 2 biomarkers versus placebo in patients with severe, uncontrolled asthma with or without perennial allergy, further supporting its efficacy in a broad population of patients with severe, uncontrolled asthma.

Introduction Le tezepelumab est un anticorps monoclonal humain bloquant l’activite de la lymphopoietine stromale thymique. Dans l’etude de phase IIb PATHWAY ( NCT02054130 ), le tezepelumab a significativement reduit les taux annualises d’exacerbations de l’asthme (AAER) de 71 % par rapport au placebo, et a ameliore la fonction pulmonaire, le controle de l’asthme et la qualite de vie chez des adultes asthmatiques severes non-controles. Cette analyse post-hoc a evalue l’effet du tezepelumab chez des patients ayant un asthme allergique qui etaient eligibles a l’omalizumab (OMA). Methodes Les patients adultes ayant un asthme severe ont ete randomises entre tezepelumab (70 mg ou 210 mg SC toutes les 4 semaines Q4S, ou 280 mg SC toutes les 2 semaines Q2S) ou un placebo Q2S pendant 52 semaines. Les patients OMA-eligibles prenaient des corticoides inhales a fortes doses, avaient un resultat positif (> 0,35 unites) aux tests immuno-enzymatiques en fluorescence concernant les aero-allergenes perennes classiques, un taux serique initial total d’immunoglobulines (Ig) E ≥ 30–≤ 1500 UI/mL, et une association d’IgE et de poids corporel le rendant eligible a l’OMA. L’AAER et le volume expiratoire maximal par seconde (VEMS) ont ete determines pour les patients eligibles et ineligibles a OMA. Resultats Sur 550 patients randomises, respectivement 92 et 453 patients ont ete eligibles et ineligibles pour le traitement par OMA (5 inconnus). Les patients OMA-eligibles avaient des taux seriques totaux initiaux d’IgE et des taux de fraction expiree du monoxyde d’azote superieurs a ceux des patients OMA-ineligibles. Comparativement au placebo, le tezepelumab 210 mg a diminue l’AAER en 52 semaines de 79% (intervalle de confiance [IC] a 95 % : 37–93) et 69 % (IC95 % : 42–83) chez les patients OMA-eligibles et OMA-ineligibles ( Fig. 1 ). Concernant le tezepelumab toutes doses confondues, l’AAER a ete reduit de 76 % (IC95 % : 46–90) et 64 % (IC95 % : 45–77) respectivement chez les patients OMA-eligibles et OMA-ineligibles. Des ameliorations du VEMS ont ete observees dans les deux groupes d’eligibilite mais les estimations ponctuelles ont ete superieures chez les patients OMA-eligibles. Conclusion Le tezepelumab a diminue les exacerbations et ameliore le VEMS comparativement au placebo chez des patients ayant un asthme allergique ou non-allergique, ce qui corrobore encore ses effets benefiques dans une large population de patients atteints d’asthme severe.

Aim of the studyMinority stress is a relatively new concept which has emerged from the earlier concept of stress. It’s popularity among researchers who are interested in minority groups is increasing. Minority stress refers to the consequences of the stigma, rejection, and violence of the majority of society as experienced by the minority. The concept can be operationalised in different ways. The first is via a questionnaire, an example of which is presented in the current article: the Sexual Minority Stress Scale (SMSS). It refers to a clearly defined concept of minority stress, and uses some indicators to of stressSubject or material and methodsThis research tool was translated and adapted to fit the Polish case. This paper presents the results of statistical analysis based on answers of 206 individuals describing themselves as homosexual and 62 describing themselves as bisexual.ResultsHigh psychometric results of the questionnaire were obtained.DiscussionHigh psychometric results of the questionnaire indicate that the SMSS can be used in research on minority stress in bisexual and homosexual individuals.ConclusionsHowever, further research is required to verify its usefulness in the clinical setting as a screening tool to diagnose those who may be at risk from high levels of minority stress.

AIM To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODS Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTS Compared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81). CONCLUSION Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.

The bicuspid aortic valve (BAV) is a congenital heart disease.The aim of study was to evaluate the assessment of atherosclerosis risk factors in adult patients with bicuspid aortic valve compared against 30 healthy, age and sex matched volunteers.Thirty patients (22 males, 8 females) at an average age of 27.00 ±10.6 years were compared against thirty healthy, age and sex matched volunteers. The arterial blood pressure, lipid profile, fasting glucose, inflammation markers and the lifestyle factors were analysed.Patients with bicuspid aortic valve have a higher level of glucose (4.95 vs 4.7 mmol / l, p = 0.026) and fibrinogen (2.25 vs. 1.98 g / l, p = 0.001) compared to the control group. In the group of patients with bicuspid aortic valve there was no hypertension, diabetes, tachycardia, stress exposure, alcohol abuse and a positive family history of cardiovascular diseases.The patients with bicuspid aortic valve have higher glucose and fibrinogen levels and they need systematic checking to reduce cardiovascular risk factors.

OBJECTIVE Introduction: Improper initial management of a victim in severe hypothermia is associated with a risk of cardiac arrest. At the same time, an uncontrolled drop in core body temperature in trauma victims is an independent risk factor for mortality. Medical personnel require a thorough understanding of the pathophysiology and treatment of hypothermia. Gaps in this understanding can lead to serious complications for patients. The aim: To compare knowledge concerning hypothermia between medical personnel working in emergency departments (ED) and emergency medical services (EMS). PATIENTS AND METHODS Materials and methods: A total of 5,362 participants were included in the study. In this study, EMS and ED personnel were encouraged to participate in an e-learning course on hypothermia. Subsequently, the scores of a pre-test, lesson tests and post-test completed by participants of this course were compared. RESULTS Results: Pre-test scores were significantly higher among personnel working in EMS compared with those working in EDs. Nurses employed in EDs had significantly more failures in completing the course than EMS nurses. The most difficult topics for all practitioners were post-traumatic hypothermia and hypothermia-related clotting disorders. CONCLUSION Conclusions: EMS personnel have a higher level of knowledge of hypothermia than ED personnel. Moreover, an e-learning course is an effective tool for improving medical personnel's knowledge of hypothermia.

The right ventricle provides systemic circulation in individuals with congenitally corrected transposition of the great arteries (CCTGA) and in those with complete transposition who have had an atrial switch repair (DTGA). The aim of this study was to evaluate how the systemic right ventricle adapts to increased workload and oxygen demand during exercise. From November 2005 through December 2015, 3,358 adult patients with congenital heart disease were treated at our institution; we identified 48 (26 females, 22 males; median age, 25.4 ± 8.1 yr) who met the study criteria; 37 had DTGA and atrial switch repair, and 11 had CCTGA. We studied their echocardiographic and cardiopulmonary exercise test results. A control group consisted of 29 healthy sex- and age-matched volunteers. On exercise testing, oxygen uptake at anaerobic threshold, peak oxygen uptake, peak heart rate, and percentage of maximal heart rate were significantly lower in the group with systemic right ventricle than in the control group (all P Our results indicate that reduced exercise capacity is related to impaired systemic right ventricular function, severe tricuspid valve regurgitation, and chronotropic incompetence. There was no correlation between cardiopulmonary exercise test results and time after surgery. Chronotropic efficiency is lower in individuals with CCTGA than in those with DTGA.

Purpose Lung ultrasound (LUS) examination is used to evaluate patients with acute respiratory failure. The physiological LUS pattern during labor in healthy parturients has not been well described. The aim of this study was to evaluate the LUS pattern in a cohort of healthy women during uncomplicated labor. Methods We used the 8-point LUS assessment protocol and investigated lung sliding, A-lines, B-lines, interstitial syndrome, lung consolidation, and pleural effusion according to the International Consensus Document with two additional supradiaphragmatic projections. All patients were screened twice; once during the first stage of labor and again within 2 hours after delivery. Results We included 24 patients in this study from February 2014 to August 2015. A total of 480 LUS records were retained for further analysis. Overall, 16 of 24 patients (67%) had at least one positive region (three or more B-lines) during the peridelivery LUS evaluation. Interstitial syndrome was detected in five patients (21%). There were no differences in A-line (P = 0.38) or B-line (P = 0.68) prevalence between LUS examinations before and after delivery. Conclusions Women in uncomplicated labor can present abnormal LUS findings, which may affect the interpretation of LUS results in patients with respiratory deterioration. Further studies should address this topic in larger cohort of patients.

The optimal programmed intermittent epidural bolus regimen for labor analgesia remains unknown. Some studies indicate that better drug spread in the epidural space results from greater injection pressure; however, there is a lack of data regarding the maximum pressure generated by epidural bolus injection using different catheters and flow rates.We evaluated the flow and pressure characteristics of 11 commonly used epidural catheters combined with 3 different infusion pumps that deliver epidural infusions according to the programmed intermittent epidural bolus regimen. Pressure changes were measured over time at flow rates of 100, 250, and 400 mL·hour and with a bolus volume of 10 mL. To account for repeated measures, linear mixed models were used. Features were selected with a backward stepwise procedure continued until only statistically significant variables were left in the model.We performed 660 measurements. The mean maximal pressure generated during bolus injection ranged from 86 to 863 mm Hg for different flow rates and catheter designs. The interaction between flow rate and catheter gauge resulted in 1.31, 1.65, and 2.00 mm Hg of pressure increase for 18G, 19G, and 20G catheters, respectively, per 1 mL·hour of increased flow rate (P.001). Analyses including wire-reinforced catheters revealed a 1.16, 1.76, and 2.36 mm Hg pressure increase for 18G, 19G, and 20G catheters, respectively, per 1 mL·hour of increased flow rate (P.001). In some cases, it triggered the occlusion pump alarm.Significant differences were observed in the in vitro maximum pressure value among the various catheter and flow rate combinations with a higher pressure value for wire-reinforced catheters used in the study. The optimal flow rate and epidural catheter combination may allow for delivery of the bolus with high flow rate without triggering the occlusion alarm.

Purpose Tezepelumab is an anti–thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V–S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V–S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI). Methods This single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18–65 years. Participants, stratified according to weight (50 to Findings A total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of Cmax, AUC0–∞, and AUC0–last were close to 1, with 90% CIs all within the range of 0.8–1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V–S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V–S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V–S, APFS, and AI groups. Median visual analog scale pain score (0–100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups. Implications Tezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V–S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V–S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.

The coarctation of the aorta (CoA) is a congenital condition of the thoracic aorta.The aim of the study was assessment of atherosclerosis risk factors in adult patients after surgical treatment of aortic coarctation.58 patients (36 male, 22 female) at median age of 27.46 ±10.57 were compared with 30 healthy, age and sex matched volunteers. The arterial blood pressure, lipid profile, fasting glucose, inflammation markers and the lifestyle factors were analyzed.CoA patients have higher systolic blood pressure 136.55±16.27 vs 123.47±10.34 mmHg, p0.001, fasting glucose 4.95±0.5 vs 4.65±0.46 mmol/l p=0.002, hsCRP 1.03±0.12 vs 0.89±0.14 mg/l p=0.025 and fibrinogen 2.55±0.34 vs 1.98±0.28 g/l p0.001. Hyperlipidemia is more common 44.8% vs 23.3% p=0.048, treated with statin. When comparing hypertensive patients (N=28) with normotensive ones (N=30), the patients with arterial hypertension are older 33.5±12.23 vs 25.73±7.12 p=0.004, have higher body weight 78.03±14.58 vs 68.7±14.29 p=0.017, in this group more common are: hypoplastic aortic arch 28.6% vs 6.7% p=0.027, recoarctation 39.3% vs 13.3% p=0.024, cardiovascular disease 14.3% vs 0% p=0.032 and family history 21.4% vs 3.3% p=0.034.The coarctation of aorta is related to higher cardiovascular risk due to arterial hypertension, hyperlipidemia, higher glucose and inflammation markers levels when comparing with healthy population.

Gastroesophageal reflux disease (GERD) is connected with body mass index (BMI) according to some recent studies. However, the link between overweight and severity of GERD symptoms is still unclear.The aim of our study is to assess the influence of BMI on clinical presentation and occurrence of inflammatory changes in the esophagus in patients with GERD.121 clinically diagnosed GERD patients: 66 males (54.5%) and 55 females (45.5%), aged 19 – 89 years were involved in the study. After the detailed anamnesis BMI was counted and gastroscopy was performed. All individuals who agreed for upper endoscopy were divided into three groups. 42 patients (34.7%) were classified as Non-Erosive Reflux Disease (NERD), 53 patients (43.8%) were diagnosed with Erosive Esophagitis (EE), 11 patients (9.1%) with Barrett’s esophagus (BE). Among EE group 34 patients were diagnosed with grade A of esophagitis according to Los Angeles scale, 17 with grade B, 2 with grade C and none with grade D. The differences between groups were assessed using statistical analysis.The mean age of patients was 50.2±12.9 years and the mean BMI was 25.5±4.2 kg/m2. Patients with BE were older (61.2±12.0 years) than NERD (48.5±13.6 years); (p=0.028) and EE (50.4±11.4 years); (p=0.008). BE had higher BMI (27.0±4.4 kg/m2) as compared to NERD (24.0±3.3 kg/m2); (p=0.022) and EE (24.4±3.1 kg/m2); (p=0.048). Hiatal hernia was more frequent in EE and BE (79.2% and 90.9%, respectively) as compared to NERD (45.2%); (p0.001). Patients EE and BE more frequently complained to heartburn (84.9% and 72.7%, respectively) than patients with no mucosal injury (42.9%); (p0.001). Sleeping problems were encountered by patients with higher levels of BMI.This study demonstrates that overweight predispose to esophageal inflammation and increase the frequency of heartburn and sleep problems in GERD patients.

The aims of this study were to translate the Michigan Hand Outcomes Questionnaire into the Polish language and to test the measurement properties of its quality criteria. A total of 120 patients with hand complaints completed the Polish Michigan Hand Outcomes Questionnaire and the Disabilities of the Arm, Shoulder, and Hand questionnaire on the first assessment, along with the grip test, pinch test, and pain sore assessed using a visual analogue scale during activity. After 7 days, 76 patients completed the Michigan Hand Outcomes Questionnaire the second time. The Cronbach alpha of the Michigan Hand Outcomes Questionnaire subscales ranged from 0.79 to 0.96. The intraclass correlation coefficient varied from 0.82–0.97, and the Bland–Altman method indicated the Michigan Hand Outcomes Questionnaire total score limit of agreement was −13.2–12.3 and −9.18–9.62 for the right and left hand, respectively. The construct validity revealed a moderate to strong correlation between every subscale of the Polish Michigan Hand Outcomes Questionnaire and Disabilities of the Arm, Shoulder, and Hand, but they only correlated with the grip test and the visual analogue scale, and neither correlated with the pinch test. The study demonstrated properties similar to the original version, validating the belief that the use of this questionnaire in medical practice in Poland is justified.

Polish Medical Air Rescue is tasked to deal with the most serious incidents associated with life threatening situations, in multiple circumstances. As a consequence, medical personnel have to meet high standards of education and show a continuous theoretical and practical development of the skills which are necessary during medical treatment. Thanks to the introduction of ECMO treatment for accidental hypothermia patients, new clinical and operational possibilities have arisen, so more patients can be saved with a very good neurological outcome.To analyze the data on hypothermia collected by the personnel of Polish Medical Air Rescue and to assess the e-learning platform as an educational tool.123 persons were involved. The subject of analysis were the e-learning platform results of the Polish Medical Air Rescue medical personnel. The e-learning consisted of a pre-test, 8 lessons followed by MCQ's (multi choice questions) and a post-test.We could not prove a statistically significant difference in the knowledge about hypothermia between doctors and other medical professionals. Post-traumatic hypothermia and associated coagulation disturbances are two important topics requiring particular focus during the design of further educational and training projects. As a consequence of the training, both groups significantly improved their knowledge: i.e. a statistically significant improvement of knowledge about hypothermia between pre-test and post-test results in both groups was shown. The hypothermia e-learning platform for medical personnel is an effective educational tool.

Aims The first aim of this study was to determine the size of the Koch's triangle. The second one was to investigate relation between its dimensions and other individual-specific and heart-specific parameters as well as to create universal formula to estimate triangle dimensions based on these parameters. Methods and results This study is a prospective one, presenting 120 randomly selected autopsied hearts dissected from adult humans (Caucasian) of both sexes (31.7% females), with mean age of 49.3 ± 17.4 years. The length of triangle sides and angles were measured and the triangle area was calculated as well. Sixteen additional heart parameters were measured in order to analyse potential relationship between the dimensions of Koch's triangle and other dimensions of the heart, using linear regression analysis. The mean (±SD) length of the anterior edge was approximated to 18.0 ± 3.8 mm, the posterior edge to 20.3 ± 4.3 mm, and the basal edge to 18.5 ± 4.0 mm. The average values of the apex angle, the Eustachian angle, and the septal leaflet angle were 58.0 ± 14.4°, 53.8 ± 10.6°, and 67.6 ± 14.4°, respectively. The mean value of the Koch's triangle area was 151.5 ± 55.8 mm2. The 95th percentile of triangle's height (the distance from the apex to the coronary sinus) was 21.8 mm. Conclusion Mean values and proportions of triangle's sides and angles were presented. Koch's triangle showed considerable individual variations in size. The dimensions of the triangle were strongly independent from individual-specific and heart-specific morphometric parameters; however, the maximum triangle's height can be estimated as 22 mm.

INTRODUCTION Insulin‑like growth factor 1 (IGF‑1) is involved in the modulation of immunity and inflammation. It also plays a role in regulating the migration of endothelial cells and production of vasoactive agents. OBJECTIVES This study assessed the concentrations of IGF‑1 and insulin‑like growth factor-binding protein 3 (IGFBP‑3) and their relationships to disease activity in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS A total of 129 adult patients with IBD (69 with Crohn disease [CD] and 60 with ulcerative colitis [UC]) were involved in the study. The control group consisted of 31 healthy volunteers. Biochemical serum analyses were performed and the associations of IGF‑1 and IGFBP‑3 with inflammatory markers and disease activity were assessed. RESULTS IGF‑1 levels were decreased in patients with active UC compared with those with nonactive UC (mean [SD], 78.3 [22.7] ng/ml and 96.2 [24.5] ng/ml, respectively; P = 0.02) and controls (94.5 [26.5] ng/ml; P = 0.03). The IGF‑1 level was lower in patients with active CD compared with those with nonactive CD (mean [SD], 79.2 [24.9] ng/ml and 110.1 [43.4] ng/ml, respectively; P

INTRODUCTION Celiac disease (CD) is an immune-mediated enteropathy related to permanent gluten intolerance, characterized by gastrointestinal symptoms as well as nongastrointestinal symptoms, including neurologic ones. The presence of neuron-specific enolase (NSE), interleukin 10 (IL-10), and antiganglioside M1 (anti-GM1) antibodies has been demonstrated for neurologic conditions as well as immune disorders with neurologic manifestations. OBJECTIVES The aim of the study was to determine the concentrations of IL-10, NSE, and anti-GM1 antibodies in the course of CD and their correlation with changes in electrogastrography (EGG) and with heart rate variability (HRV). PATIENTS AND METHODS The study included 68 participants: 34 patients with CD and 34 healthy individuals. We assessed the concentrations of IL-10 and NSE as well as the presence of anti-GM1 antibodies in serum. We investigated correlations between the concentrations of IL-10, NSE, and anti-GM1 antibodies and the results of EGG and HRV. RESULTS Patients with CD had a higher level of anti-GM1 antibodies than controls (1.38 ng/ml [0.98-2.03 ng/ml] vs 0.81 ng/ml [0.35-1.15 ng/ml]). Median IL-10 concentrations in patients with CD differed significantly from those in controls (7 pg/ml [4.33-11.48 pg/ml] vs 4.27 pg/ml [2.44-7 pg/ml]; P = 0.010). In HRV analysis, a positive correlation between IL-10 concentrations and very low frequency spectrum was observed (r = 0.63; P = 0.003). There was no correlation between the concentrations of IL-10, NSE, or anti-GM1 antibodies and EGG parameters. CONCLUSIONS Chronic inflammation in the course of CD may lead to autonomic nervous system impairment and development of neurologic disorders. Therefore, anti-GM1 antibodies and IL-10 may be considered as markers of nervous system impairment in the course of CD.

INTRODUCTION Celiac disease (CD) is an immune-mediated enteropathy related to permanent gluten intolerance, characterized by gastrointestinal symptoms as well as nongastrointestinal symptoms, including neurologic ones. The presence of neuron-specific enolase (NSE), interleukin 10 (IL-10), and antiganglioside M1 (anti-GM1) antibodies has been demonstrated for neurologic conditions as well as immune disorders with neurologic manifestations. OBJECTIVES The aim of the study was to determine the concentrations of IL-10, NSE, and anti-GM1 antibodies in the course of CD and their correlation with changes in electrogastrography (EGG) and with heart rate variability (HRV). PATIENTS AND METHODS The study included 68 participants: 34 patients with CD and 34 healthy individuals. We assessed the concentrations of IL-10 and NSE as well as the presence of anti-GM1 antibodies in serum. We investigated correlations between the concentrations of IL-10, NSE, and anti-GM1 antibodies and the results of EGG and HRV. RESULTS Patients with CD had a higher level of anti-GM1 antibodies than controls (1.38 ng/ml [0.98-2.03 ng/ml] vs 0.81 ng/ml [0.35-1.15 ng/ml]). Median IL-10 concentrations in patients with CD differed significantly from those in controls (7 pg/ml [4.33-11.48 pg/ml] vs 4.27 pg/ml [2.44-7 pg/ml]; P = 0.010). In HRV analysis, a positive correlation between IL-10 concentrations and very low frequency spectrum was observed (r = 0.63; P = 0.003). There was no correlation between the concentrations of IL-10, NSE, or anti-GM1 antibodies and EGG parameters. CONCLUSIONS Chronic inflammation in the course of CD may lead to autonomic nervous system impairment and development of neurologic disorders. Therefore, anti-GM1 antibodies and IL-10 may be considered as markers of nervous system impairment in the course of CD.

The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear.

Background: The goal of this study was to assess the relationship between sociocultural factors and clinical eating disorders during the intensive process of Westernisation in Poland that occurred after 1989. The study population included girls diagnosed with an eating disorder according to DSM-IV criteria (n = 47 anorexia nervosa restrictive type [ANR], n = 16 anorexia binge/purge type [ANBP], n = 34 bulimia nervosa [BN], n = 19 eating disorder not otherwise specified [EDNOS]) who received consultation for the first time between 2002 and 2004 in the Department of Clinical Child and Adolescent Psychiatry, University Hospital, Kraków, Poland. The study included an age-matched normal control group [NOR] of 85 schoolgirls from Kraków. Methods: Relationships between two given qualitative features were investigated using the chi-square test or Fisher’s exact test. Correspondence analysis was applied to graphically explore the relationship. The Kruskal-Wallis test with the Bonferroni was performed to compare quantitative results across groups. Results: Objective sociodemographic variables and responses to the 62-item Questionnaire of Socio-cultural Context were measured. The mothers of ANBP and BN patients were less professionally active than mothers of ANR patients and NOR subjects. Subjective socio-cultural factors were more relevant for the BN group than the ANR group. Questionnaire responses in the ANBP group were more similar to those in the BN group than to those in the ANR group. The most unambiguous and specific characteristic of the ANR group was a sense of belonging to the middle class. Variables that differentiated the BN group from the NOR group included the importance attached to thinness treated as an expression of power and control over one’s self, as well as a multifaceted negative evaluation of one’s own family, including a negative assessment of the position of women and parental lack of concern for appearance and principles of nutrition. All patients, regardless of diagnosis, identified with other people with similar problems and considered anorexia and bulimia to be a major issue of their generation and social environment. Conclusions: The results of this first in Poland exploratory study of socio-cultural context of eating disorders indicate the importance of both objective and subjective socio-cultural factors in eating disorders in the group studied.

INTRODUCTION In patients with inflammatory bowel disease (IBD), disbalance between procoagulant, anticoagulant, and fibrinolytic factors has been shown. The hemostatic system is an indispensable component of the inflammatory process. Deficiencies in the protein C (PC) pathway components not only promote thrombosis, but also exacerbate inflammation. OBJECTIVES The aim of the study was to assess the components of the PC system and their correlations with disease activity in patients with IBD. PATIENTS AND METHODS The levels of PC, free protein S (PS), and soluble thrombomodulin (sTM) were measured in 55 consecutive patients with ulcerative colitis (UC), 50 patients with Crohn's disease (CD), and 41 healthy volunteers. Correlations between PC system components and disease activity, hemostatic variables, and inflammatory markers were assessed. RESULTS sTM levels in patiens with UC were higher compared with controls (24.5 vs. 17.5 ng/ml; P = 0.0042). In patients with IBD, PC activity was higher and PS activity was lower compared with controls (P

The divergence entropy: O/T and O/R measuring the distance between observed/theoretical and observed/random distributions was applied to identify the category of protein structures in respect to the hydrophobic core in protein molecules. The naive interpretation was applied treating the proteins of O/T < O/R as the molecules of hydrophobic core accordant with the theoretically assumed. The proteins of O/T > O/R are treated as representing the hydrophobic core not accordant with the assumed one. The large scale computing was performed (PDB data set) to reveal whether other than simple inequality relation should be used for this identification. The cluster analysis was applied to identify the relation O/T versus O/R as the discrimination factor to classify the category of proteins in respect to their structural form of hydrophobic core.

The cluster analysis is applied to the analysis of the data describing the status of protein structure in respect to hydrophobic core characteristics. The analysis revealed presence of two clusters distinguishing the proteins accordant with the “fuzzy oil drop” model and those which appear as discordant in respect to this model. The analysis was performed separately for chains treated as structural unit and for units defined according to IV-order (taking the functional protein complex). The characteristics of these two classification system appeared to differ in respect to number of proteins belonging to each of two clusters as well as relation between them.

Source of support: The presented research is part of a larger research project entitled “Socio-cultural, familial, and individual factors in anorexia and bulimia nervosa”, which is financed by a scientific grant from the State Committee for Scientific Research (Grant Number: 6 POSE 09021) Summary Background: The aim of this study was to assess attitudes towards eating as measured by the Eating Attitude Test (EAT26) among mothers of girls diagnosed with various types of eating disorders, in comparison with mothers of depressive girls and their relationship with daughters’ results 14 years after the beginning of the Polish political and cultural transformation of 1989. Material/Methods: The data of 68 mothers and their daughters were used in statistical analysis (anorexia nervosa restrictive type: 18, anorexia nervosa binge/purge type: 12, bulimia: 14, depression: 24). The mean age in the group of mothers was 43.5 (SD 5.3), daughters: 16.7 (SD 1.4). Results: In the group of mothers, the results of EAT26 test were lower than results of the general population of Polish females or patients’ mothers obtained in a different cultural context. Results from girls with an eating disorder diagnosis considerably exceed the mean result of Polish population studies of teenagers. There were no statistically significant differences between the EAT26 results of mothers of girls with various types of eating disorders and mothers of depressive girls. Sociocultural variables such as education and place of residence of mothers also did not differentiate the studied groups and did not have a significant influence on attitudes towards weight and body shape presented by the studied mothers. Conclusions: The obtained results may suggest that in the studied population, the social background of mothers and disturbances of their own mothers’ attitudes towards weight and body shape were not an important and specific risk factor in the development of their daughters’ eating disorders.

f ),Zdzislaw Wisniowski a ),Kinga Salapa a a ) 1 ) a The three-dimensional structures of a set ofnever born proteins� (NBP, random amino acid sequence proteins with no significant homology with known proteins) were predicted using two methods: Rosetta and the one based on thefuzzy-oil-drop� (FOD) model. More than 3000 different random amino acid sequences have been generated, filtered against the non redundant protein sequence data base, to remove sequences with significant homology with known proteins, and subjected to three- dimensional structure prediction. Comparison between Rosetta and FOD predictions allowed to select the ten top (highest structural similarity) and the ten bottom (the lowest structural similarity) structures from the ranking list organized according to the RMS-D value. The selected structures were taken for detailed analysis to define the scale of structural accordance and discrepancy between the two methods. The structural similarity measurements revealed discrepancies between structures generated on the basis of the two methods. Their potential biological function appeared to be quite different as well. The ten bottom structures appeared to beunfoldablefor the FOD model. Some aspects of the general characteristics of the NBPs are also discussed. The calculations were performed on the EUChinaGRID grid platform to test the performance of this infrastructure for massive protein structure predictions. Introduction. - The search for techniques aimed at the generation of new proteins for pharmacological and biotechnological applications is widely developed nowadays (1 - 3). This involves the selection of proteins of desirable activity among those present in Nature, as well as the production of new polypeptide compounds resulting from libraries of peptides with random amino acid sequences (4) (5). The final aim of these

Background: Altered eicosanoid metabolismis a characteristic finding of aspirin induced asthma (AIA). Oral aspirin challenge is confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. Objectives: The influence of aspirin on sputum supernatant concentration of eicosanoids during the oral challenge test was studied, using chromatography-mass spectrometry measurements. Methods: Induced sputum was collected before and following oral aspirin challenge. Sputum differential cell count and sputum supernatant concentrations of prostaglandin E 2 (PGE 2 ) was measured. Results: Aspirin precipitated bronchoconstriction was reported in all AIA (n=15) subjects, but in none of HC (n=13) and ATA (n=15). AIA was characterized by the dominance of the eosinophilic airway inflammation, whereas the paucigranulocytic phenotype was most frequent in HC. At baseline, mean induced sputum supernatant level of PGE 2 did not differ between the groups. Following the challenge, PGE 2 decreased in asthmatics patients independent of aspirin hypersensitivity (AIA p=0.002; ATAp=0.02), but not in HC (p=0.07). Cumulative doses of aspirin or the duration of the challenge had no effect on the magnitude of the PGE 2 alterations. Conclusions: During the oral aspirin challenge, PGE 2 decreases significantly in asthmatics as compared to healthy ones. The results support the theory on the inhibition of PGE 2 biosynthesis as a trigger for bronchoconstriction mediated by cysteinyl leukotrienes in AIA.

article Background: The coronary sinus ostium (CSO) is covered by the Thebesian valve (ThebV), which has a variable shape when assessed subjectively. The ThebV is an anatomical barrier during CS cannulation, which may be complicatedduetothevalves'size.The typesofvalvesare:cord,remnant,semilunar,fold,andmesh/fenestrated. The ThebV can be visible using multisliced computed tomography (MSCT), however, this method cannot show the ThebV's morphological shape, only its size. Methods: 301 randomly selected autopsied human hearts were examined. The shape of the valve was subjectively assessed, whereas the ThebV height (H) and the CSO diameter (D) were measured. The H/D-Ratio was computed as the ThebV height divided by the CSO diameter, afterwards k-means cluster analysis was performed to estimate H/D- Ratio's range of values between valves. MSCT scans from 114 patients that underwent CSO cannulation were objectively evaluated based on similar measured parameters in accordance with received H/D-Ratio values. Results: Boundaries of ratio evaluations between remnant and semilunar, and semilunar and fold types were 0.35 and 0.65 respectively. In MSCT scans, the ThebV was recorded in 61 cases (remnant = 5.3%, semilunar = 24.6%, fold = 16.7%, cord = 0.0%, mesh/fenestrated = 7.9%). Except for the remnant and cord types, the other types appear similarly as in the cadaveric and MSCT studies. There were no differences between ThebV height and the CSO diameter in cadavers and MSCT studies. Conclusion: The H/D-Ratio can be useful in assessing ThebV shape as visualized in MSCT. We give threshold values for the H/D-Ratio which easily allow the ThebV shape to be determined.

Hyperhomocysteinemia seems to be a common phenomenon in both patients with ulcerative colitis and Crohn's disease. Many factors including deficiencies of cobalamin, folate and pyridoxine, smoking habits, alcohol and coffee intake, some medications and age may predispose subjects to hyperhomocysteinemia. The study aimed to evaluate homocysteine levels in an inflammatory bowel disease cohort as dependent of life style and disease activity.85 consecutive patients with inflammatory bowel disease (38 with Crohn's disease and 47 with ulcerative colitis) and 65 control subjects were included in the prospective study. The following parameters were analyzed: disease activity, duration of the disease, location of pathological changes, presence of complications, current medications, past surgical procedures, smoking history, concomitant diseases, biochemical parameters and plasma homocysteine levels.Mild hyperhomocysteinemia was found in 16 patients with Crohn's disease (42%), 19 patients with ulcerative colitis (40%) and 19 patients in the control group (29%) (p = 0.59). There was not any significant correlation between homocysteine level and disease activity. Only folic acid supplementation and gender affected homocysteine level. Folic acid intake led to reduction of homocysteine levels in all groups of patients (11.8 micromol/l vs. 8.33 miccromol/l, p = 0.0065 in Crohn's disease patients and 10.94 micromol/l vs. 7.78 micromol/l, p = 0.0069 in ulcerative colitis patients).Homocysteine level in patients with inflammatory bowel disease is mostly normal or slightly elevated. Disease activity does not have an impact on homocysteine level. Folic acid is the most important factor having an influence on homocysteine level in patients with inflammatory bowel disease.

The aim of the study was to assess the relationship between depressive symptoms and girls' assessment of their family relations in a group of (female) patients with a diagnosis of various subtypes of eating disorders in comparison with (female) patients with a diagnosis of depressive disorders (episode of major depression, dysthymia, adjustment reaction with depressive mood) and female students in Krakow, Poland schools.Data from 54 (female) patients with a diagnosis of restrictive anorexia (ANR), 22 with a diagnosis of binge-purge anorexia (ANB), 36 with a diagnosis of bulimia (BUL), 36 with a diagnosis of depressive disorders (DEP) and a 85 (female) Krakow school students (CON) were used in the statistical analyses. There were no significant differences between age of the girls in studied groups. In analyses, results of the Polish version of the Beck Depression Inventory (BDI) and also the Family Assessment Questionnaire (KOR) were used.In the CON group, correlations attesting to a link between depressiveness and a negative assessment of the family were observed on all scales of the questionnaire with the exception of the Values and Norms scale. In the DEP group, such a dependence was ascertained on scales: Completing Tasks, Communication, Emotionality, Control, Defence, Positive Statements. In the case of the ANR group, no statistically significant relationship between results of the questionnaires was noted. In group ANB, correlations attesting to a link between depressiveness and a negative picture of the family were ascertained on scales: Communication and Defence. The same dependence was ascertained in the BUL group on scales: Completing Tasks, Emotionality, Emotional involvement, Control, General result, Negative Statements.An increase in depressiveness is linked in a significant way with a worsening assessment of the family relations amongst girls with a diagnosis of bulimia, depressive disorders and students.

BACKGROUND Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolism. Its mechanism is still unclear. Altered fibrin clot properties have been reported in patients with thromboembolism and those with chronic inflammatory states. We investigated whether fibrin characteristics are abnormal in IBD. METHODS Ex vivo plasma fibrin clot permeability (Ks), compaction, turbidity, and efficiency of fibrinolysis were assessed in 85 consecutive patients with IBD, including 47 with ulcerative colitis (UC) and 38 with Crohn's disease (CD), all with no history of thromboembolism. Forty-eight patients matched for age and sex served as controls. RESULTS Compared with controls, patients with UC and CD had 29.5% and 35.7% lower Ks associated with 13.8% and 23.1% lower compaction, respectively (all P < 0.001). Patients with UC and CD had higher maximum clot absorbance (+8.9%, P = 0.008, and +15.2%, P < 0.0001, respectively), higher maximum D-dimer released from clots (D-D(max), +27.0%, P = 0.01, and +28.7%, P < 0.0001, respectively), and prolonged clot lysis time (+19.0%, P < 0.0001, and +25.5%, P < 0.0001, respectively). Lag phase was similar in both group of patients. D-D(max) was the only parameter that differed between patients in the UC and CD groups, being higher in CD (P = 0.04). The multiple linear regression model showed that in patients with UC, but not with CD, Ks, compaction, lysis time, and D-D(max) were all independently associated with disease activity. In patients with CD, Ks and lysis time were independently predicted by fibrinogen and C-reactive protein. CONCLUSIONS Both UC and CD are characterized by formation of dense fibrin networks relatively resistant to lysis. Prothrombotic clot phenotype might represent a novel mechanism increasing thrombotic risk in IBD.

This paper presents a method for determining the structure of the early stage (ES) intermediate in the multistage protein folding process. ES structure is modeled on the basis of a limited conformational subspace of the Ramachandran plot. The model distinguishes seven structural motifs corresponding to seven local probability maxima within the limited conformational subspace. Three of these are assigned to well-defined secondary structures, while the remaining four are found to represent various types of random coils. The presented heuristic approach also provides insight into the reasons behind incorrect predictions occurring when the folding process depends on external factors (e.g., ligands, ions or other proteins) rather than on the characteristics of the backbone itself. The accuracy of the presented method is estimated at around 48 %.

This article examines the effectiveness of artificial neural networks (ANNs) as forensic voice comparison techniques. This study specifically considers feed-forward multilayer perceptron (MLP) and radial basic function (RBF) network models. Formant frequencies of Polish vowel e (stressed or unstressed) in selected contexts were used as predictors. This has already been confirmed in an earlier investigation that determined that dynamic formant frequencies of vowels are powerful elements in distinguishing the voice. It has been concluded that neural networks might assist in distinguishing speakers from the others with very good accuracy, reaching 100%. MLP models should be given preference. The results of the investigation have shown the influence of vowel e triads on the effectiveness of correct classification rates. In addition, the authors have determined that the accuracy of classification is greater when based on a single context than for similar input data aggregated over several different contexts.

To assess cultural attitudes and beliefs among (female) patients being treated for various kinds of eating disorders in comparison with (female) patients diagnosed with depression and healthy girls.Version II of the Cultural Questionnaire by M. Pilecki and B. Józefik referring to issues linked with those aspects of dulture whose importance is described as significant in the development of eating disorders.Data from patients with the following diagnoses were used in the statistical analyses: 54 (female) patients with a diagnosis of restrictive anorexia (ANR), 22 with a diagnosis of binge-purge anorexia (ANB), 36 with a diagnosis ofbulimia (BUL) and 40 with a diagnosis of depressive disorders (DEP) and also 74 female pupils from Kraków schools (KON).Groups ANB and BUL obtained high scores, indicating the greater significance of 'ideals of thinness' in their lives than in groups KON, DEP and ANR. The BUL group was characterised by a sense of yielding to fashion pressure and also by a sense of the environmental and generational significance of the disorders in relation to groups KON and DEP. The females in group KON assessed that their parents attached greater importance to appearance than did (female) patients in group ANB. A negative evaluation of the position of women in the family was given by all the studied (female) patients in comparison with group KON.The obtained results may indicate the greater significance of cultural mechanisms in bulimia than anorexia nervosa. They may also be an expression of the limited possibility of introspection of girls with a diagnosis of restrictive anorexia. A negative perception of femininity in the family and culture accompanies not only eating disorders, but also depressive disorders.

To the Editor: The risk of thromboembolic events is 3 to 4-fold higher in patients with inflammatory bowel disease (IBD) than in the general population.1 Venous thromboembolism in IBD occurs usually during exacerbation mainly in patients with more advanced complicated forms of the disease.1 The mechanisms underlying the link of IBD and thromboembolism involve endothelial injury, procoagulant effects of enhanced inflammation, hyperhomocysteinemia, and genetic predisposition.2 Typical prothrombotic abnormalities reported in IBD include elevated fibrinogen, factors (F)V, FVIII, FIX, FXIII, impaired fibrinolysis as well as reduced anticoagulant proteins such as protein S.2,3 Recently, it has been suggested that arterial thrombosis is more prevalent in IBD than in the general population.4 Tissue factor (TF) is the main initiator of blood coagulation in vivo. Although it has been suggested that circulating TF-bearing microparticles are elevated in IBD like in other inflammatory disorders,5 to our knowledge there have been no reports regarding TF levels in Crohn’s disease (CD) or ulcerative colitis (UC) patients. Moreover, increased active FXI (FXIa) levels that are known to confer a higher risk of venous and arterial thrombosis,6 have been observed in patients with active UC.5 No data on FXIa in CD have been published yet. To evaluate a potential role of procoagulant activity of TF and FXIa, we studied 80 consecutive IBD patients (39M, 41F) aged 34.5±12.1 years (±SD) (range 18 to 69), including 34 subjects with CD and 46 with UC. Active disease was observed at the time of enrollment in 19 CD patients (mean activity 169.2±93.5) and 26 UC assessed using a variation of the Truelove-Witts criteria (mean activity 5.45±3.35). Exclusion criteria were as follows: any acute illness, cancer, hepatic or renal dysfunction, previous venous thromboembolism, MI or stroke, oral anticoagulation or heparin administration. The Jagiellonian University Ethical Committee approved the study, and patients provided written, informed consent. To determine FXIa and TF in fasting citrated plasma, we used inhibitory monoclonal anti-FXI (αFXI-2) and anti-TF (αTF-5) antibodies at a final 0.1 mg/ml concentration and measured clotting time as previously described.7 The quantitation limit of our TF activity assay is 0.4 pM and that of FXIa assay is 10 pM. Age- and sex-matched healthy individuals (n=12) recruited from the hospital staff showed no detectable TF or FXIa. To assess thrombin generation in plasma, we determined thrombin-antithrombin complexes (TAT) using an ELISA (Dade Behring, Marburg, Germany). Quantifiable amounts (>10 pM) of plasma FXIa were detected in 53 of 80 (66%) patients with IBD. The concentration of FXIa varied from 17 to 156 pM with an average value of 57.2±33.6 pM. Detectable plasma TF activity was displayed in 27 of 80 (34%) IBD patients, all of whom also had circulating FXIa in plasma. Only 10 IBD patients had TF activity above 0.5 pM in the range from 0.6 to 5.1 pM. The concentration of TF in the remaining samples was below 0.4 pM. TF-positive patients did not differ from those not displaying detectable TF activity in plasma with regard to demographics, fibrinogen, C-reactive protein, creatinine, and disease activity (data not shown). This also held true for FXIa-positive and -negative patients with IBD except for age: the patients with detectable FXIa were older (36.6±12.7 years) than those with no FXIa (30.7±10.0 years, p=0.028). Importantly, plasma TAT correlated with FXIa in IBD (r2=0.49, p