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Claire Emson,1 Jonathan Corren,2 Kinga Sałapa,3 Åsa Hellqvist,4 Jane R Parnes,5 Gene Colice6 1Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 2David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; 3Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland; 4Biometrics, Late-Stage Development, Respiratory and Immunology, AstraZeneca, Gothenburg, Sweden; 5Amgen, Thousand Oaks, CA, USA; 6Late-Stage Development Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USACorrespondence: Claire EmsonAstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USATel +13013980304Email Claire.emson@astrazeneca.comBackground: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis, from binding to its heterodimeric receptor. In the phase 2b PATHWAY study, tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control, in adults with severe, uncontrolled asthma. This post hoc analysis assessed the efficacy of tezepelumab in adults with severe, uncontrolled asthma with and without nasal polyposis (NP).Methods: In this post hoc analysis of the PATHWAY study (NCT02054130), participants (N=550) were randomized 1:1:1:1 to receive subcutaneous tezepelumab 70 mg every 4 weeks (Q4W), 210 mg Q4W or 280 mg every 2 weeks (Q2W), or placebo Q2W, for 52 weeks. The AAER over 52 weeks and the change from baseline to week 52 in blood eosinophil count, fractional exhaled nitric oxide (FeNO) levels and serum levels of interleukin (IL)-5 and IL-13 with tezepelumab 210 mg (the phase 3 dose) and placebo were analyzed in patients grouped by self-reported presence (NP+) or absence (NP−) of NP at screening.Results: At baseline, NP+ patients had higher blood eosinophil counts, higher FeNO levels and higher serum IL-5 and IL-13 levels than NP− patients. Tezepelumab 210 mg reduced the AAER versus placebo to a similar extent in both NP+ and NP− patients (NP+, 75% [95% confidence interval (CI): 15, 93], n=23; NP−, 73% [95% CI: 47, 86], n=112). Patients treated with tezepelumab 210 mg demonstrated greater reductions in blood eosinophil count and levels of FeNO, IL-5 and IL-13 than placebo-treated patients, irrespective of NP status.Discussion: Tezepelumab reduced exacerbations and reduced type 2 inflammatory biomarkers in patients with and those without NP, supporting its efficacy in a broad population of patients with severe asthma.Keywords: asthma, biomarkers, nasal polyps, sinusitis, tezepelumab, thymic stromal lymphopoietin

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: AstraZeneca and Amgen., Competing Interests: Declaration of interests MEW is an employee of US National Jewish Health and has received consultancy fees from AstraZeneca, Equillium, Genentech, GlaxoSmithKline, Novartis, Regeneron, resTORbio, Sanofi, and Teva. AM-G has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, and Teva; has received speaker fees from AstraZeneca, Novartis, Roche, and Teva; participated in research with AstraZeneca, for which his institution has been remunerated; has attended international conferences with Teva; and has consultancy agreements with AstraZeneca, Sanofi, and Vectura. CEB has received grants and consultancy fees from AstraZeneca. PK has received personal fees for lectures from Adamed, Alvogen, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, HAL Allergy, LEK-AM, Menarini Group, Mylan, Novartis, Polpharma, Sanofi, and Teva. SK has received fees for lectures and advisory board meetings from AstraZeneca, GlaxoSmithKline, Novartis, Roche, Sanofi Aventis, and Teva. TW has received fees for lectures and advisory board meetings from AstraZeneca, Berlin-Chemie, GlaxoSmithKline, MSD, Novartis, Roche, and Sanofi Aventis. JMG, KS, ÅH, GA, HL, TS, and GC are employees of AstraZeneca. PK is an employee of Amgen., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022 AstraZeneca and Amgen Inc. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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 FEV 1 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 FEV 1 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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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: 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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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 <70 kg, 70 to <80 kg, or 80-90 kg), were randomized evenly to 9 groups representing injections to the abdomen, thigh, or upper arm via V-S, APFS, or AI. Tezepelumab PK parameters over 113 days were evaluated after a single 210-mg SC dose. The primary end points were comparison of C max and AUC 0-∞ between device groups. Further PK parameters, immunogenicity, safety (including injection site reactions [ISRs] and injection site pain [visual analog scale]) were also assessed., Findings: A total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of C max , AUC 0-∞ , and AUC 0-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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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 evaluate an impact of bicuspid aortic valve concomitance on arterial stiffness results. Methods: Fifty-eight patients after coarctation of aorta repair, 36 male, median age of 27.46 ± 10.57, were compared to 30 with bicuspid aortic valve and to 30 healthy, sex, age and BMI matched volunteers. Physical examination, laboratory analysis and non-invasive assessment of arterial stiffness were performed. Results: CoA patients and BAV patients have higher central arterial stiffness parameters in comparison to healthy controls: AP (7.86 ± 6.56 vs 7.68 ± 5.96 vs 1.41 ± 3.82 mmHg, p  < 0.001, p  = 0.011, respectively) and AIx (18.81 ± 14.94 vs 18.06 ± 13.38 vs 4.41 ± 10.82%, p  < 0.001, p  = 0.006, respectively). There were no differences of PWV between CoA patients, BAV patients and healthy controls (6.07 ± 1.20 vs 5.95 ± 1.20 vs 5.67 ± 0.73 m/s, p  = 0.099, p  = 0.278, respectively). In CoA group, there was correlation of PWV with age ( r  = 0.55 p  < 0.001), BMI ( r  = 0.29, p  = 0.025), fibrinogen ( r  = 0.31, p  = 0.039), glucose ( r  = 0.58, p  < 0.001), ascending aorta diameter ( r  = 0.29, p  = 0.026) and age at operation ( r  = 0.27, p  = 0.041). Among group of BAV, there was a correlation of PWV with age ( r  = 0.58, p  < 0.001), central AP with total cholesterol ( r  = 0.38, p  = 0.036) and fibrinogen ( r  = 0.41, p  = 0.024). Conclusions: The increased arterial stiffness occurs in both groups: patients after aortic coarctation repair and patients with bicuspid aortic valve. Concomitance of coarctation of the aorta and bicuspid aortic valve has no influence on arterial stiffness augmentation.

Background: 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., Methods: 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., Results: 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., Conclusions: 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: 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., (© 2019 Wiley Periodicals, Inc.)

The bicuspid aortic valve (BAV) is a congenital heart disease., Aim: 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., Materials and Methods: 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., Results: 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., Conclusions: The patients with bicuspid aortic valve have higher glucose and fibrinogen levels and they need systematic checking to reduce cardiovascular risk factors., (© 2019 MEDPRESS.)

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.

Podsiadło, Paweł, Sylweriusz Kosiński, Tomasz Darocha, Kinga Sałapa, Tomasz Sanak, and Hermann Brugger. The use of e-learning in medical education for mountain rescuers concerning hypothermia. High Alt Med Biol 19:272-277, 2018., Objective: Victims of mountain accidents are often exposed to wet and cold environments which may increase the risk of hypothermia. Mountain rescuers should be able to recognize and manage hypothermia. We aimed to assess relevant knowledge in professional and volunteer mountain rescuers, as well as to evaluate the efficacy of an e-learning platform for continuing medical education., Methods: An e-learning platform was developed to provide access to updated information about hypothermia. Volunteer and professional mountain rescuers participated in an e-learning course. Pretest, post-test, and specific lesson test scores were compared. After 1 year, a follow-up course was performed., Results: In total, 187 rescuers, comprising 136 (72.7%) volunteers and 51 (27.3%) professionals, were enrolled. Ahead of the course, no difference in knowledge was found between professionals and volunteers. After the course, one's knowledge of hypothermia increased significantly (p < 0.001). The scores achieved in the field management of hypothermia were better among professional rescuers than among volunteer rescuers (p = 0.003), whereas in post-traumatic hypothermia half of the results were insufficient in both groups. Moreover, 57 rescuers repeated the course after 12 months. While professionals partially retained the achieved level of knowledge, the volunteers had dropped back to their initial level., Conclusions: The e-learning course increased the knowledge of hypothermia among mountain rescuers. The poor retention after 1 year indicates that the interval between lectures should be reduced. An e-learning platform is an effective tool for the medical education of mountain rescuers.

The coarctation of the aorta (CoA) is a congenital condition of the thoracic aorta., Aim: The aim of the study was assessment of atherosclerosis risk factors in adult patients after surgical treatment of aortic coarctation., Materials and Methods: 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., Results: CoA patients have higher systolic blood pressure 136.55±16.27 vs 123.47±10.34 mmHg, p<0.001, 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 p<0.001. 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., Conclusions: 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., (© 2018 MEDPRESS.)

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.

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 <0.001). The IGFBP‑3 level was lower in patients with active UC compared with those with nonactive UC (P = 0.04) and controls (P = 0.04). IGF‑1 correlated negatively with C‑reactive protein (CRP) levels (P <0.01), disease activity (P <0.05), and disease duration (P <0.05). IGFBP‑3 levels correlated negatively with CRP levels (P <0.05). CONCLUSIONS    The IGF system is disrupted in patients with IBD. Systemic levels of the IGF axis components are related to disease activity and duration.

Podsiadło, Paweł, Tomasz Darocha, Sylweriusz Kosiński, Kinga Sałapa, Mirosław Ziętkiewicz, Tomasz Sanak, Rachel Turner, and Hermann Brugger. Severe hypothermia management in mountain rescue: A survey study. High Alt Med Biol 18:411-416, 2017., Introduction: Severe hypothermia is a rare but demanding medical emergency. Although mortality is high, if well managed, the neurological outcome of survivors can be excellent. The aim of the study was to assess whether mountain rescue teams (MRTs) are able to meet the guidelines in the management of severe hypothermia, regarding their equipment and procedures., Methods: Between August and December 2016, an online questionnaire, with 24 questions to be completed using Google Forms, was sent to 123 MRTs in 27 countries., Results: Twenty-eight MRTs from 10 countries returned the completed questionnaire. Seventy-five percent of MRTs reportedly provide advanced life support (ALS) on-site and 89% are regularly trained in hypothermia management. Thirty-two percent of MRTs transport hypothermic patients in cardiac arrest to the nearest hospital instead of an Extracorporeal Life Support facility; 39% are equipped with mechanical chest compression devices; 36% measure core body temperature on-site and no MRT is equipped with a device to measure serum potassium concentration on-site in avalanche victims., Conclusions: Most MRTs are regularly trained in the treatment of severe hypothermia and provide ALS. The majority are not equipped to follow standard procedural guidelines for the treatment of severely hypothermic patients, especially with cardiac arrest. However, the low response rate-23% (28/123)-could have induced a bias.

Fast and accurate measurement of core body temperature is crucial for accidental hypothermia treatment. We have developed a novel light and small adapter to the headset jack of a mobile phone based on Android. It has been applied to measure temperature and set up automatic notifications (e.g. Global Positioning System coordinates to emergency services dispatcher, ECMO coordinator). Its validity was confirmed in comparison with Vital Signs Monitor Spacelabs Healthcare Elance 93300 as a reference method, in a series of 260 measurements in the temperature range of 10-42 °C. Measurement repeatability was verified in a battery of 600 measurements (i.e. 100 readings at three points of 10, 25, 42 °C for both esophageal and tympanic catheters). Inter-method difference of ≤0.5 °C was found for 98.5% for esophageal catheter and 100% for tympanic catheter measurements, with concordance correlation coefficient of 0.99 for both. The readings were almost completely repeatable with water bath measurements (difference of ≤0.5 °C in 10 °C: 100% for both catheters; in 25 °C: 99% for esophageal catheter and 100% tympanic catheter; in 42 °C: 100% for both catheters). This lightweight adapter attached to smartphone and standard disposable probes is a promising tool to be applied on-site for temperature measurement in patients at risk of hypothermia.

Background: Recently, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become the rewarming treatment of choice in hypothermic cardiac arrest. The detailed indications for extracorporeal rewarming in non-arrested, severely hypothermic patients with circulatory instability have not been established yet. The primary purpose of the study was a preliminary analysis of all aspects of the treatment process, as well as initial identification of mortality risk factors within the group of severely hypothermic patients, treated with arteriovenous extracorporeal membrane oxygenation (VA-ECMO). The secondary aim of the study was to evaluate efficacy of VA-ECMO in initial 6-h period of treatment METHODS: From July 2013 to June 2016, thirty one hypothermic patients were accepted for extracorporeal rewarming at Severe Accidental Hypothermia Center, Cracow. Thirteen patients were identified with circulatory instability and were enrolled in the study. The evaluation took into account patients' condition on admission, the course of therapy, and changes in laboratory and hemodynamic parameters., Results: Nine out of 13 analyzed patients survived (69%). Patients who died were older, had lower both systolic and diastolic pressure, and had increased creatinine an potassium levels on admission. In surviving patients, arterial blood gases parameters (pH, BE, HCO 3 ) and lactates would normalize more quickly. Their potassium level was lower on admission as well. The values of the core temperature on admission were comparable. Although normothermia was achieved in 92% of patients, none of them had been weaned-off VA-ECMO in the first 6 h of treatment., Discussion and Conclusions: In our preliminary study more pronounced markers of cardiocirculatory instability and organ hypoperfusion were observed in non-survivors. Future studies on indications to extracorporeal rewarming in severely hypothermic, non-arrested patients should focus on the extent of hemodynamic disturbances. Short term (<6 h) treatment in severe hypothermic, non-arrested patients seems to be not clinically appropriate.

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., Aim: 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., Materials and Methods: 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., Results and Conclusions: 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.

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.

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.

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.

Introduction: 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., Objectives: 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., Material and Methods: 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., Results: 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%); (p<0.001). Patients EE and BE more frequently complained to heartburn (84.9% and 72.7%, respectively) than patients with no mucosal injury (42.9%); (p<0.001). Sleeping problems were encountered by patients with higher levels of BMI., Conclusion: This study demonstrates that overweight predispose to esophageal inflammation and increase the frequency of heartburn and sleep problems in GERD patients.

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 complicated due to the valves' size. The types of valves are: cord, remnant, semilunar, fold, and mesh/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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusion: 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.

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 %.

Aim: 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., Method: 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., Results: 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., Conclusions: 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: 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.

Aim: 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., Method: 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., Material: 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)., Results: 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., Conclusions: 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.

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 <0.001). Tumor necrosis factor α (TNF-α) levels were higher in patients with IBD, and interleukin 6 (IL-6) levels were higher only in patients with CD. In patients with UC, a positive correlation was observed between sTM and both PC and PS levels (r = 0.28 and r = 0.34, respectively, P <0.05). Only PC levels correlated with UC activity (r = 0.3, P <0.05). No correlations of TNF-α, IL-6, and C-reactive protein with PC, PS, and sTM levels were observed., Conclusions: The PC pathway is defective in patients with CD and UC. Hypercoagulability in IBD might be associated not only with the inflammatory process but also with disturbances in the anticoagulant system, since defective PC pathway was observed both in active and nonactive disease.

The proteins composed of short polypeptides (about 70 amino acid residues) representing the following functional groups (according to PDB notation): growth hormones, serine protease inhibitors, antifreeze proteins, chaperones and proteins of unknown function, were selected for structural and functional analysis. Classification based on the distribution of hydrophobicity in terms of deficiency/excess as the measure of structural and functional specificity is presented. The experimentally observed distribution of hydrophobicity in the protein body is compared to the idealized one expressed by a three-dimensional Gauss function. The differences between these two distributions reveal the specificity of structural/functional characteristics of the protein. The residues of hydrophobicity deficiency versus the idealized distribution are assumed to indicate cavities with the potential to bind ligands, while the residues of hydrophobicity excess are interpreted as potentially participating in protein-protein complexation. The distribution of hydrophobicity irregularity seems to be specific for particular structures and functions of proteins. A comparative analysis of such profiles is carried out to identify the potential biological activity of proteins of unknown function.

The three-dimensional structures of a set of 'never 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 the 'fuzzy-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 be 'unfoldable' for 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.