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The aim of the research was a spatial and functional analysis of the accessibility of retail food environments in relation to the inhabitants of dispersed settlements who are socially and geographically disadvantaged in purchasing g food. The consumer behavior and food shopping habits of the inhabitants of these areas largely depend on the spatial and functional characteristics of the dispersed settlement and the surrounding area. In terms of food consumption, an important determinant is the availability of convenience stores, defined by the economic and physical ability to access food sources. The ability to access stores is strongly influenced by transport options and transport infrastructure. The investigated area belongs to a group of specific areas with dispersed settlements. This type of settlement, typical in the mountains of Slovakia and on the border with the Czech Republic, can also be found around the town of Nová Baňa, located in the west of central Slovakia. This area consists of two towns and 12 municipalities and is referred to as the “Novobanská štálová oblasť ”. These specific territories are characterized by a lack of access to fresh and affordable food, which can contribute to social disparities in diet and endanger people's health with various serious diseases. Spatial identification of areas with difficult access to food stores in the Novobanská štálová area has been a pioneering attempt to visualize areas with the highest demand for improvement in food access, and this process may be helpful in identifying other areas with similar characteristics. The methods utilized represent an accessible, transparent and reproducible process for assessing the accessibility of grocery stores. These methods can be used for cost-effective, periodic surveillance and meaningful engagement with communities, retailers and policy makers. The conclusions and results of our research should positively contribute to the growing debate on the inequality of living conditions and marginalization of rural municipalities.

The regeneration through meristem culture is an advanced biotechnological technique which is a very useful and valuable method and represents a key in the fruit stock material production chain. In the modern fruit planting material production system and in the pathogen elimination systems it occupies a central place. In this article we will present the main aspects regarding the behavior of some plum cultivars in the process of the in vitro meristem culture: initiation, multiplication, acclimation. It is well known the fact that the propagation of woody fruit species and in general that of stone fruit species is difficult through tissue cultures and especially the propagation systems through meristems. For initation there has been used four variants concerning two nutritive media and two apex sizes, one of 0.2-0.8 mm. The culture media was MS medium (Murashige and Skoog, 1967) with two different hormone concentration 0,7 mg/l BAP and 2 mg/l BAP. The biological material used was represented by apices isolated from annual shoots of 25 cm harvested in autumn at cultivars V1- Jubileu 50, V2-Ivan, V3-Iulia, V4- Geta. For multiplication it has been used two variants of nutritive media: MS and WPM with 0,7 mg BAP concentration. The rooting formula used was MS media with 0.7 mg/l BAP, 1 mg/l 1BA, 1 mg/l B1 vitamin, 30 g/l saccharose. [ABSTRACT FROM AUTHOR]

In the report we concentrate on the influences of water-induced morphodynamic processes and surface flow on the development of tarns in alpine environment conditions of selected valleys in the High Tatras. Model areas are represented by higher basins parts in the Malá Studená valley and the Veľká Studená valley, where we confirmed that slope-gravitational processes in the form of rockfall, water-gravitational processes in the form of debris flows, but also fluvial-proluvial processes as the accumulation of the soft fractions from the area of debris cones take part in the material deposition in the tarns. In this context we focused on the creation of the model of spatial distribution of the water-induced potential of material deposition in drainage tarn basins. The model includes three basic factors: slope and curvature of the relief and land cover character. Map processing with GIS technologies was done on the basis of a 3-D relief model, which allowed the locating of the local erosion bases areas, where the material could be accumulated. The achieved results confirmed the hypothesis that tarn basin development of the alpine environment is subordinated to permanent backfilling as a consequence of the cumulative influence of the several processes connected with rainfall and the runoff regime of the drainage basins.

During the years 2010-2012, we observed the spatial activity of long-eared owls by the radio telemetry in an agricultural land. The average home range size of tracked long-eared owls for 100 and 95% minimum convex polygon (MCP) was 415.93 and 350 ha, respectively. Between the breeding and the non-breeding season, we did not record significant differences in the size of home ranges. Open land units (meadows and arable lands) belonged to the most abundant land units in the home ranges of tracked owls (mean for 100 and 95% MCP was 24.6 and 24.3%, respectively). Forest edges with their ecotone character also represented the abundant land unit (mean for 100 and 95% MCP was 11.4 and 10.6%, respectively). An amount of built-inhabited areas in home ranges (mean for 100 and 95% MCP was 8.2 and 10.1%, respectively) correlated positively with their size (Spearman rank correlation: for 100% MCP: rs = 0.83, p

The paper presents a Kalman filtering problem for discrete–time linear systems with parametric uncertainties. A stochastic model with multiplicative noise both in the state and in the output equations is used to represent the system with uncertain parameters. The solution of the filtering problem is a Kalman type filter which gain is determined by solving the H2 optimization problem for the resulting system obtained by coupling the filter with the stochastic system. It is proved that the optimal gain of the filter may be computed by solving a trace minimization problem with constraints expressed in terms of a system of matrix inequalities. The proposed filtering approach is illustrated by a case study aiming to estimate the states of the pitch dynamics of a space launch vehicle in its center of mass.

Successful micropropagation of black chokeberry (Aronia melanocarpa) cultivars ‘Nero’, ‘Melrom’ and ‘Galicjanka’ was realized using young shoots with the aim of an optimized hormones concentration for initiation, multiplication and rooting phases. Good potential of initiation was observed at ‘Nero’ and ‘Galicjanka’ cultivars, respectively of shoots regeneration at ‘Galicjanka’ and ‘Melrom’ cultivars. Results showed that the use of antioxidant solutions is crucially in the initiation phase in order to prevent explants oxidation. Good initiation rates were obtained at ‘Nero’ (57 %) and ‘Galicjanka’ (57%) cultivars, while for ‘Melrom’ the rate was only 33% by using a hormonal balance of 0.7 mg/L BAP and a reduced level of 0.3 mg/L GA3. The in vitro shoots multiplication rate was relatively stable during the first subcultures. Best micropropagation rates were obtained at ‘Galicjanka’ and ‘Melrom’ cultivars followed by ‘Nero’ cultivar, using a 0.7 mg/L BAP and 0.5 mg/L GA3. The study showed also that, rooting process is enhanced when the culture medium contains activated charcoal (1.2 g/L) and a lower IBA concentration (0.5 mg/L) compared with the application of higher auxin concentration of the same hormone (1.0 mg/L). Activated charcoal seems to promote a good rooting process, thus being very important in the rooting phase. Researches revealed that the genotype influences the capacity of inoculums regeneration, the multiplication capacity and the rooting ability.

Objectives: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs., Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured., Results: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76)., Conclusions: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Meaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries., Methods: Built on previous research findings on potential barriers, a prioritisation survey was conducted online with CEE stakeholders. Recommendations for prioritised barriers were formed through a face-to-face workshop by CEE stakeholders and HTx experts., Results: A total of 105 stakeholders from 13 CEE countries completed the prioritisation survey and identified 12 of the 22 potential barriers as highly important. The workshop had 36 participants representing 9 CEE countries, and 5 Western European countries coming together to discuss solutions in order to form recommendations based on best practices, real-life experience, and transferability aspects. Stakeholder groups involved in both phases included HTA organisation representatives, payers, patients, caregivers, patient organisation representatives, patient experts, health care providers, academic and non-academic researchers, health care consultants and health technology manufacturers/providers. As a result, 12 recommendations were formed specified to the CEE region's context, but potentially useful for a broader geographic audience., Conclusion: In this paper, we present 12 recommendations for meaningful, systematic, and sustainable patient involvement in HTA in CEE countries. Our hope is that engaging more than a hundred CEE stakeholders in the study helped to spread awareness of the importance and potential of patient involvement and that the resulting recommendations provide tangible steps for the way forward. Future studies shall focus on country-specific case studies of the implemented recommendations., Competing Interests: Patient involvement should be open to all and non-discriminative on the grounds of previous experience and presumed support time needed. There are multiple initiatives locally and internationally aiming to ease patient recruitment with education, coordination and/or databases. We recommend organisations leading these initiatives to come together and join forces on the base of commonly agreed principles. We also recommend local HTA/payer organisations to set up their open call for local patients, carers, patient advocates, patient experts and patient organisation representatives to be able to express interest. We suggest to actively promote this opportunity to harder to reach patient communities and a periodical revision of the registry. Regarding ethical and compliance issues, a clear policy on financial and other conflicts of interests (how interests are declared, assessed and addressed) should be in place. Those registered should complete a declaration of interest form both on personal and organisational level conflict of interests and update it periodically. It should be clarified what kind of involvement with industry (e.g., attending a single advisory board meeting with a company versus only in case of direct conflict of interest) would impose restrictions on how a person can be involved in the HTA and decision-making process. We argue that in situations where patient experts and/or patient organisation representatives are difficult to identify, a softer approach should be taken and special measures could be proposed, equivalent to the “expert witness” status at the European Medicines Agency (EMA). Expert witnesses can be heard or participate in the deliberations but are not allowed to take part in the vote. However, the consequences of not being transparent with potential conflict of interests should be serious and communicated clearly from the beginning.KrT, RH, ZP, BN, and ZK were employed by Syreon Research Institute. At the time of the study IJ was the President of the European Patients’ Forum Youth Group, a Board of Trustees member at the EUPATI Foundation and employed by Syreon Research Institute. MN is the founder and co-owner of HealthQuest, a health technology assessment and market access consulting company. DaD is a Trustee of Thrombosis UK. TB was employed by Patvocates GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jakab, Dimitrova, Houÿez, Bereczky, Fövényes, Maravic, Belina, Andriciuc, Tóth, Piniazhko, Hren, Gutierrez-Ibarluzea, Czech, Tesar, Niewada, Lorenzovici, Kamusheva, Manova, Savova, Mitkova, Tachkov, Németh, Petykó, Dawoud, Delnoij, Knies, Goettsch and Kaló.)

Background and Objective: Several novel methods have been suggested to extend a conventional value assessment to capture a more comprehensive perspective of value from a patient perspective. The objective of this research was to demonstrate a framework for implementing a combined qualitative and quantitative method to elicit and prioritize patient experience value elements in rare diseases. Neuromyelitis optica spectrum disorder was used as a case study., Methods: The method for eliciting and prioritizing patient experience value elements involved a three-step process: (1) collecting potential patient experience value elements from existing literature sources followed by deliberation by a multi-stakeholder research team; (2) a pre-workshop webinar and survey to identify additional patient-reported value elements; and (3) a workshop to discuss, prioritize the value elements using a swing weighting method. Outcomes were prioritized value elements with normalized weights for patients considering a treatment for neuromyelitis optica spectrum disorder., Results: A literature review and deliberation resulted in the following initial value elements: ability to reach important personal milestones, patient's financial burden, value of hope/balance or timing of risks and benefits, Uncertainty about long-term benefits and safety of the treatment, Patient empowerment through therapeutic advancement and technology, Caregiver/family's financial burden, patient experience related to treatment regimen, Therapeutic options, and Caregiver/family's quality of life. Eight patients with neuromyelitis optica spectrum disorder participated in the case study. In the online survey, participants found the nine proposed patient experience value elements both understandable and important with no additions. During the workshop, 'Uncertainty about long-term benefits and safety,' 'Patient experience related to treatment regimen,' and 'Patient's financial burden' were found to be the most important patient experience value elements, with a respective weight of 25%, 19.2%, and 14.4% (out of total 100%)., Conclusions: This case study provides a framework for eliciting and prioritizing patient experience value elements using direct patient input. Although elements/weights may differ by disease, and even in neuromyelitis optica spectrum disorder, additional research is needed, value frameworks, researchers, and manufacturers can use this practical method to generate patient experience value elements and evaluate their impact on treatment selection., (© 2022. The Author(s).)

Objectives: Decision-aids (DAs) may facilitate shared decision-making for patients and caregivers, by providing evidence-based information to assist healthcare professionals, patients, and caregivers in making choices about aspects of care, and/or highlighting decision factors to discuss with the potential of altering the treatment decision. These decision factors may not be well integrated in DAs., Methods: A systematic literature review was conducted in the field of multiple myeloma (MM) on peer-reviewed publications, extended with a gray literature search. Data on whether and how patient and caregiver experience elements, other than survival and physical quality of life, were mentioned as decision factors in the identified MM DAs were extracted and analyzed qualitatively., Results: Seventy MM DAs were found and analyzed; 51% of DAs mentioned any patient non-routinely assessed experience decision factors and only 17% mentioned any caregiver-related information. One hundred and forty potential decision factors were extracted, deduplicated and categorized into the following categories: 1) financial, 2) mode of administration / transportation issues, 3) personal beliefs and values, 4) emotional and social quality of life, 5) other medical information, 6) availability of social support, 7) caregiver burden. None of the DAs presented a comprehensive framework on all seven categories of decision factors being consider when mapping patient and caregiver experience value elements in MM., Conclusions: Based on available DAs, we recommend a set of patient and caregiver experience decision factors that have the potential to affect treatment choices of patients with MM, which should be included in DAs, including MM clinical guidelines., (Copyright © 2022. Published by Elsevier Inc.)

Patients' perspectives are important to identify preferences, estimate values and appreciate unmet medical needs in the process of research and development and subsequent assessment of new health technologies. Patient and public involvement in health technology assessment (HTA) is essential in understanding and assessing wider implications of coverage and reimbursement decisions for patients, their relatives, caregivers, and the general population. There are two approaches to incorporating the patients' voice in HTA, preferably used in a mix. In the first one, patients, caregivers and/or their representatives directly participate at discussions in different stages of the HTA process, often at the same table with other stakeholders. Secondly, patient involvement activities can be supported by evidence on patient value and experience collected directly from patients, caregivers and/or their representatives often by patient groups Patient involvement practices, however, are limited in Central and Eastern European (CEE) countries without clear methodology or regulatory mechanisms to guide patient involvement in the HTA process. This poses the question of transferability of practices used in other countries, and might call for the development of new CEE-specific guidelines and methods. In this study we aim to map potential barriers of patient involvement in HTA in countries of the CEE region., Competing Interests: Authors IJ, AZ, BN, and ZK are employed by Syreon Research Institute. At the time of the study IJ was the President of the European Patients' Forum Youth Group and a Board of Trustees member at the EUPATI Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dimitrova, Jakab, Mitkova, Kamusheva, Tachkov, Nemeth, Zemplenyi, Dawoud, Delnoij, Houýez and Kalo.)

Background: Chronic pelvic pain (CPP) is a common condition which significantly impacts the quality of life and wellbeing of many women. Laparoscopy with histopathology is recommended for investigation of pelvic pain and identification of endometriosis with concurrent removal. Never-the-less, the association between endometriosis and pelvic pain is challenging, with endometriosis identified in only 30-50% of women with pain., Aims: To explore the predictors for undergoing surgery, for identifying endometriosis and endometriosis severity in a cohort of women with CPP., Materials and Methods: This study forms part of the Persistent Pelvic Pain project, a prospective observational cohort study (ANZCTR:ACTRN12616000150448). Women referred to a public gynaecology clinic with pain were randomised to one of two gynaecology units for routine care and followed for 36 months with 6-monthly surveys assessing demographics, medical history, quality of life, and pain symptoms measured on a Likert scale. Operative notes were reviewed and endometriosis staged., Results: Of 471 women recruited, 102 women underwent laparoscopy or laparotomy, of whom 52 had endometriosis (n = 37 stage I-II; n = 15 Stage III-IV). Gynaecology unit, pelvic pain intensity and lower parity were all predictors of surgery (odds ratio (OR) 0.342; 95% CI 0.209-0.561; OR 1.303; 95% CI: 1.079-1.573; OR 0.767; 95% CI: 0.620-0.949, respectively). There were no predictors identified for endometriosis diagnosis and the only predictor of severity was increasing age (OR 1.155; 95% CI: 1.047-1.310)., Conclusions: Gynaecology unit and pain intensity were key predictors of undergoing laparoscopy; however, pain severity did not predict endometriosis diagnosis or staging. These findings indicate the need to review current frameworks guiding practice toward surgery for pelvic pain., (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

This study aimed to investigate the potential application of image texture processing method on visible crumb structure of salty cake pogácsa, which was prepared with different baking times (5 and 7 min) and temperatures (200, 215, and 230°C). For this purpose, changes in gray level co-occurrence matrix (GLCM) features including energy, contrast, correlation, homogeneity, and entropy were monitored and their relationship with the instrumental texture parameters (hardness, adhesiveness, cohesiveness, springiness, gumminess, and chewiness) were assessed. The pore ratios were also extracted and visualized using image processing technique. Texture profile parameters indicated strong correlation (p < .01) with the image pattern parameters in different pogácsa groups. Gumminess showed strong correlation with contrast (0.503), correlation (-0.498), and homogeneity (0.401). Hardness also exhibited correlation with contrast (0.517), entropy (0.341), and correlation (-0.476). The pore ratio showed marked variation in crumb structure when different times and temperatures were used. Baking at 230°C for 7 min maximized the pore ratio (0.56). Penalty analysis revealed that oiliness, pore structure, and color of products were linked with baking time and temperature. Overall, the results suggested that the GLCM-based technique had the potential to be used as a nondestructive method for rapid quality assessment of pogácsa., (© 2021 Wiley Periodicals LLC.)

BACKGROUND: Inclusion of patient experience (PEx) in health technology assessment (HTA) has become increasingly important; however, no harmonized approach exists to help manufacturers or decision makers ensure PEx considerations are fair, consistent, and thorough within global HTA frameworks. OBJECTIVE: To develop a proposal for including PEx in the HTA frameworks of health technologies. METHODS: A systematic literature review (SLR) on existing value frameworks (VFs) was conducted to capture how PEx-related value judgment is currently considered. Guided by the results of the SLR, a research group including HTA experts and patient representatives used an iterative process to develop potential value domains to capture PEx, in accordance with international guidelines. Subsequently, a panel of international payer experts was used to challenge the proposed PEx domains and provide recommendations for implementation. RESULTS: The SLR found 61 VFs and multi-criteria decision analyses (MCDAs) that considered PEx; however, PEx-related value elements were often referred to superficially, without clear definitions. Five potential PEx domains, with proposed measures for each, were developed and refined using expert feedback: (1) responsiveness to patient's individual needs, (2) improved health literacy and empowerment, (3) patient and caregiver reported outcomes, (4) household's financial burden, and (5) improved access for vulnerable patient populations. A flexible approach for framework implementation was proposed. CONCLUSIONS: Proposed PEx domains could be implemented at multiple levels of healthcare decision making to formalize consideration of PEx in the assessment of value, either through the extension of existing VFs or to create new PEx-focused VFs and more holistic decision making tools. DISCLOSURES: This study was funded and sponsored by UCB Pharma. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. Charokopou, Mountain, and Szegvari are employed by UCB Pharma. Inotai, Jakab, and Kalo are employed by Syreon Research Institute, which received funding from UCB Pharma for this research. Brixner has received fees from AbbVie, Elevar, Millcreek Outcomes Group, Novartis, Sanofi, UCB Pharma, and Xcenda. Campbell has received grants and contracts from the PhRMA Foundation and the Institute for Clinical and Economic Review. During a sabbatical leave, Campbell collaborated with Syreon Research Institute on research projects that included funding from UCB Pharma. Hawkins has received consultancy fees from UCB Pharma. Kristensen has received speakers bureau fees from Pfizer, AbbVie, Amgen, UCB Pharma, Celgene, Bristol-Myers Squibb, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals and consultancy fees from UCB Pharma.

Background: Defining the value of healthcare is an elusive target, and depends heavily on the decision context and stakeholders involved. Cost-utility analysis and the quality-adjusted life year (QALY) have become the method and value definition of choice for traditional value judgements in coverage and pricing decisions. Other criteria that may influence value are often not measured and therefore omitted from value assessments, or are only used to qualitatively contextualize assessments. The objective of this study was to engage two key stakeholders; patients and payers to elicit and rank the importance of additional value criteria, potentially assessed in Multiple Criteria Decision Analysis (MCDA). Methods: This study consisted of a focus group with cancer patients ( n = 7), including follow-up questions through an electronic survey, and in-depth phone interviews with payers ( n = 5). Results: For payers, value equated either with criteria that provided tangible benefits (from their perspective) such as new treatment options that respond to serious unmet need. For patients, population-level value equated to options that would potentially benefit them in the future and the value of hope. However, these criteria were seen by payers as difficult to measure and incorporate into objective decision making. Limitations: The findings from this study are primarily limited due to generalizability. Due to the small sample size, it was outside the scope of this study to calculate a weight for each criterion that could be used as part of a quantitative MCDA. Conclusion: MCDA, with particular attention to qualitative aspects, is an avenue to incorporate these additional criteria into value assessments, as well as provide an opportunity for reflecting the patient's preferences in assessing the value of a treatment., Competing Interests: Author SR was employed by the company Real Endpoints, LLC. Author IJ and ZK were employed by Syreon Research Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jakab, Whittington, Franklin, Raiola, Campbell, Kaló and McQueen.)

Background: Multicriteria Decision Analysis (MCDA), a formal decision support framework, has been growing in popularity recently in the field of health care. MCDA can support pricing and reimbursement decisions on the macro level, which is of great importance especially in countries with more limited resources., Objectives: The aim of this systematic review was to facilitate the development of future MCDA frameworks, by proposing a set of criteria focusing on the purchasing decisions of single-source innovative pharmaceuticals in upper middle-income countries., Methods: A systematic literature review was conducted on the decision criteria included in value frameworks (VFs) or MCDA tools. Scopus, Medline, databases of universities, websites of Health Technology Assessment Agencies, and other relevant organizations were included in the search. Double title-abstract screening and double full-text review were conducted, and all extracted data were double-checked. A team of researchers performed the merging and selection process of the extracted criteria., Results: A total of 1,878 articles entered the title and abstract screening. From these, 341 were eligible to the full-text review, and 36 were included in the final data extraction phase. From these articles 394 criteria were extracted in total. After deduplication and clustering, 26 different criteria were identified. After the merging and selection process, a set of 16 general criteria was proposed., Conclusion: Based on the results of the systematic literature review, a pool of 16 criteria was selected. This can serve as a starting point for constructing MCDA frameworks in upper middle-income countries after careful adaptation to the local context., (Copyright © 2020 Jakab, Németh, Elezbawy, Karadayı, Tozan, Aydın, Shen and Kaló.)

The total polyphenolic content and the antioxidant activity have been analyzed in ground beans of green, light, medium and dark roasted coffee by UV-VIS spectrometry. Water coffee extracts showed the highest levels of polyphenols in green and light roasted coffees where the total polyphenolic content (TPC) ranged from 49.19 ± 0.70 to 74.05 ± 0.28 and from 59.79 ± 1.45 to 38.34 ± 1.26 g GAE.kg -1 , respectively. In medium roast samples it ranged from 43.90 ± 3.07 to 74.05 ± 0.28g GAE.kg -1 and in dark roast from 37.44 ± 0.63 to 47.41 ± 0.69 g GAE.kg -1 . The total antioxidant capacity (TAC) reached the highest values (DPPH inhibition ranging from 69.08 ± 1.33% to 78.55 ± 0.89%) in light roasted coffees. Dark roasted coffees showed both the lowest content of polyphenols as well as the total antioxidant capacity. In case of TPC, statistically significant differences (P˂0.001) have been identified between green coffee and other roasted degrees. Also, dark coffee showed statistically noticeable differences (P˂0.001) in TPC in relation to other roasted stages. Statistically important difference (P˂0.001) has been discovered between the total antioxidant capacity of dark roasted coffee and other roasting levels. The results demonstrated that roasting process affects both the oxidative activity as well as polyphenolic content.

The Societe de Psychopathologie de L'Expression (SIPE) was founded in 1959 in Verona, Italy, during the International Congress on Lombroso. Robert Volmat asked us to get together for discussing the possibility of establishing a society for the research of the art of the insane. The author introduces the most important events and publications after the initiation of the research on the psychopathology of expression.

We studied whether non-adrenergic, non-cholinergic (NANC) relaxation of the rabbit sphincter of Oddi was influenced by tolerance to nitroglycerin (NG) in vitro. Sphincter of Oddi (SO) muscle rings precontracted with EC50 concentrations of cholecystokinin octapeptide (CCK8) were exposed to cumulative increases in NG concentrations and tested for relaxation by measurement of isometric tension. A separate group of six rings was subjected to a preceding exposure to 275 microM nitroglycerin over 60 min to induce in vitro tolerance to nitroglycerin. The rings (both tolerant and non-tolerant) were subjected to electrical field stimulation (FS: 50 V, 0.1 ms, 20 Hz, 3 and 10 stimuli). The rings were then preincubated with NANC solution: phentolamine, oxprenolol and atropine (all 1 microM) for 20 min and FS was applied again. FS was repeated after additional incubation with NG-nitro-L-arginine methyl ester (L-NAME), and inhibitor of NO synthase (30 microM) and after a successive incubation with 3 mM L-arginine (20 min). Maximum contractions produced by CCK8 in 'tolerant' and 'non-tolerant' sphincters were 29.9 +/- 5.8 and 28.3 +/- 5.2 mN, respectively. The sensitivity to CCK8 also was not different between the two groups with EC50 (-log M) values of 8.5 +/- 0.2 and 8.3 +/- 0.1, respectively. FS evoked twitchlike contraction followed by relaxation in the ampullary SO in both 'tolerant' and 'non-tolerant' preparations. Incubation in NANC solution resulted in monophasic relaxations in response to FS in non-tolerant sphincters but not in tolerant ones. L-NAME (30 microM) reversed NANC relaxation in non-tolerant muscle rings whereas it failed to modify NANC contractions in the tolerant preparations. L-arginine (3 mM) reversed the inhibitory effect of L-NAME on NANC relaxation in the 'non-tolerant' rings and it was without effect on FS-induced contractions in the 'tolerant' SO. As measured by radioimmunoassay, tolerance to NG was without any significant effect on tissue content of both cyclic adenosine 3':5' monophosphate (cAMP) and cyclic guanosine 3':5' monophosphate (cGMP). FS significantly increased tissue cAMP and cGMP content in 'non-tolerant' preparations. FS failed to increase the level of either cyclic nucleotide in 'tolerant' tissue. We conclude that NANC relaxation of the ampullary part of the rabbit SO is significantly impaired in the state of tolerance to NG 'in vitro'.

In this article we studied whether the nitrergic relaxation of the rabbit sphincter was sensitive to glibenclamide. Field stimulation relaxed the sphincter of Oddi rings after incubation with atropine (1 microM) and guanethidine (4 microM) with threefold and fourfold increases in tissue guanosine 3':5'-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate contents, respectively. These changes were blocked by 30 microM NG-nitro-L-arginine methyl ester. Glibenclamide (0.1-10 microM) attenuated the field stimulation-induced relaxation and completely abolished the relaxation produced by 0.1 microM cromakalim. We conclude that nitrergic relaxation of the rabbit sphincter of Oddi comprises a mechanism sensitive to glibenclamide., (Copyright 1997 The Italian Pharmacological Society.)

We studied the role of the L-arginine-nitric oxide (NO) pathway in non-adrenergic, non-cholinergic (NANC) relaxation of the rabbit sphincter of Oddi by recording changes in isometric tension in response to electrical field stimulation in two series of experiments. In a first set of experiments, biliary sphincters of Oddi removed from New Zealand white rabbits were placed horizontally in an organ bath containing oxygenized, buffered (pH 7.4) Krebs solution. Contractile responses of the whole sphincter to field stimulation were determined. In the second set of experiments, sphincter of Oddi was divided into two parts and the effects of field stimulation were studied separately on areas close to the duodenal papilla (area I) and areas close to the common bile duct (area II). In the whole sphincter of Oddi, field stimulation induced an initial twitch-like contraction followed by relaxation proportional to the number of stimuli (3 and 10 stimuli at 20 Hz, 50 V, 0.1 ms). The magnitude of the contractile responses was considerably reduced by 1 microM atropine, phentolamine and oxprenolol (NANC solution). Field stimulation produced dose-dependent contractions of both segments of sphincter of Oddi in response to the same protocol as used with whole sphincter of Oddi. However, preincubation with NANC solution produced monophasic relaxations in response to field stimulation in area I, whereas area II preparations such as the whole sphincter of Oddi responded with contractions followed by minimal relaxations. Field stimulation failed to induce either contractions or relaxations in the presence of 1 microM tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial ischemia assessed by intracavital ST-segment elevation, shortening of ventricular effective refractory period (VERP), and increase in left ventricular end-diastolic pressure (LVEDP) was provoked by ventricular overdrive pacing (VOP) in conscious rabbits. Cromakalim (10 micrograms/kg), an ATP-sensitive K+ channel opener, and cicletanine (30 mg/kg), a cGMP-phosphodiesterase inhibitor, reduced VOP-induced ST-segment elevation and LVEDP-increase. Under resting conditions, cromakalim lowered blood pressure, increased heart rate (HR), and shortened VERP, whereas cicletanine decreased HR, prolonged VERP without changing blood pressure. Co-administration of cromakalim and cicletanine additively reduced VOP-induced ST-segment elevation, shortening of VERP, and LVEDP-increase. Cicletanine did not change cromakalim-induced hypotension but abolished reflexogenic tachycardia. This suggests that VERP shortening is not a prerequisite for the anti-ischemic effect of cromakalim, and the combination of these drugs may afford a potent and safe anti-ischemic effect without affecting hypotension induced cromakalim.

Background: This study examined whether cicletanine, an antihypertensive drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits., Methods: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation and ventricular effective refractory period (VERP). PQ and QT intervals were measured in the chest-lead ECG, and dP/dtmax as well as left ventricular end-diastolic pressure (LVEDP) were recorded through a left intraventricular catheter. In separate groups, mean arterial blood pressure (MABP) was monitored from the right carotid artery. Experiments were performed on conscious rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after drug treatment and/or overdrive pacing for determination of cGMP and cAMP contents by radioimmunoassay., Results: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dtmax, and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VERP. Overdrive pacing produced intracavital ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. Cicletanine administered 15 minutes before pacing significantly attenuated ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. In anesthetized animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacing., Conclusions: These results suggest that in correlation with alterations of cardiac cycle nucleotide contents, cicletanine protects the heart against pacing-induced myocardial ischemia.

In conscious rabbits equipped with right ventricular electrode and left ventricular polyethylene catheters, zaprinast and cicletanine, inhibitors of phosphodiesterase (PDE) V and PDEs I and V, respectively, as well as verapamil, a Ca2+ channel blocker, decreased intracavital ST-segment elevation induced by ventricular overdrive pacing (VOP). Zaprinast and cicletanine attenuated VOP-induced QT reduction and increase in left ventricular end-diastolic pressure (LVEDP), whereas verapamil increased LVEDP. These results suggest that inhibition of cGMP-PDEs can protect heart against ischemia.