Inositol-Exchange Activity in Human Primordial Placenta.

Human placenta is an intensively growing tissue. Phosphatidylinositol (PI) and its derivatives are part of the signaling pathway in the regulation of trophoblast cell differentiation. There are two different enzymes that take part in the direct PI synthesis: phosphatidylinositol synthase (PIS) and inositol exchange enzyme (IE). The presence of PIS is known in the human placenta, but IE activity has not been documented before. In our study, we describe the physiological properties of the two enzymes in vitro. PIS and IE were studied in different Mn2+ and Mg2+ concentrations that enabled us to separate the individual enzyme activities. Enzyme activity was measured by incorporation of 3[H]inositol in human primordial placenta tissue or microsomes. Optimal PIS activity was achieved between 0.5 and 2.0 mM Mn2+ concentration, but higher concentrations inhibit enzyme activity. In the presence of Mg2+, the enzyme activity increases continuously up to a concentration of 100 mM. PIS was inhibited by nucleoside di- and tri-phosphates. PI production increases between 0.1 and 10 mM Mn2+ concentration. The incorporation of [3H]inositol into PI increased by 57% when adding stabile GTP analog. The described novel pathway of inositol synthesis may provide an additional therapeutic approach of inositol supplementation before and during pregnancy.

Natural disturbance regimes as a guide for sustainable forest management in Europe.

In Europe, forest management has controlled forest dynamics to sustain commodity production over multiple centuries. Yet over-regulation for growth and yield diminishes resilience to environmental stress as well as threatens biodiversity, leading to increasing forest susceptibility to an array of disturbances. These trends have stimulated interest in alternative management systems, including natural dynamics silviculture (NDS). NDS aims to emulate natural disturbance dynamics at stand and landscape scales through silvicultural manipulations of forest structure and landscape patterns. We adapted a "Comparability Index" (CI) to assess convergence/divergence between natural disturbances and forest management effects. We extended the original CI concept based on disturbance size and frequency by adding the residual structure of canopy trees after a disturbance as a third dimension. We populated the model by compiling data on natural disturbance dynamics and management from 13 countries in Europe, covering four major forest types (i.e., spruce, beech, oak, and pine-dominated forests). We found that natural disturbances are highly variable in size, frequency, and residual structure, but European forest management fails to encompass this complexity. Silviculture in Europe is skewed toward even-aged systems, used predominately (72.9% of management) across the countries assessed. The residual structure proved crucial in the comparison of natural disturbances and silvicultural systems. CI indicated the highest congruence between uneven-aged silvicultural systems and key natural disturbance attributes. Even so, uneven-aged practices emulated only a portion of the complexity associated with natural disturbance effects. The remaining silvicultural systems perform poorly in terms of retention compared to tree survivorship after natural disturbances. We suggest that NDS can enrich Europe's portfolio of management systems, for example where wood production is not the primary objective. NDS is especially relevant to forests managed for habitat quality, risk reduction, and a variety of ecosystem services. We suggest a holistic approach integrating NDS with more conventional practices.

Unfolding the effects of different forestry treatments on microclimate in oak forests: results of a 4-yr experiment.

A stable below-canopy microclimate of forests is essential for their biodiversity and ecosystem functionality. Forest management necessarily modifies the buffering capacity of woodlands. However, the specific effects of different forestry treatments on site conditions, the temporal recovery after the harvests, and the reason for the contrasts between treatments are still poorly understood. The effects of four different forestry treatments (clear-cutting, retention tree group, preparation cutting, and gap-cutting) on microclimatic variables were studied within a field experiment in a managed oak-dominated stand in Hungary, before (2014) and after (2015-2017) the interventions by complete block design with six replicates. From the first post-treatment year, clear-cuts differed the most from the uncut control due to the increased irradiance and heat load. Means and variability of air and soil temperature increased, air became dryer along with higher soil moisture levels. Retention tree groups could effectively ameliorate the extreme temperatures but not the mean values. Preparation cutting induced slight changes from the original buffered and humid forest microclimate. Despite the substantially more incoming light, gap-cutting could retain the cool and humid air conditions and showed the highest increase in soil moisture after the interventions. For most microclimate variables, we could not observe any obvious trend within 3 yr. However, soil temperature variability decreased with time in clear-cuts, while soil moisture difference continuously increased in gap- and clear-cuts. Based on multivariate analyses, the treatments separated significantly based mainly on the temperature maxima and variability. We found that (1) the effect sizes among treatment levels were consistent throughout the years, (2) the climatic recovery time for variables appears to be far more than 3 yr, and (3) the applied silvicultural methods diverged mainly among the temperature maxima. Based on our study, the spatially heterogeneous and fine-scaled treatments of continuous cover forestry (gap-cutting, selection systems) are recommended. By applying these practices, the essential structural elements creating buffered microclimate could be more successfully maintained. Thus, forestry interventions could induce less pronounced alterations in environmental conditions for forest-dwelling organism groups.

Pravastatin induces NO synthesis by enhancing microsomal arginine uptake in healthy and preeclamptic placentas.

BACKGROUND: Pravastatin, a known inducer of endothelial nitric-oxide synthase (eNOS) was demonstrated in human placenta, however the exact mechanism of it's action is not fully understood. Since placental NO (nitric oxide) synthesis is of primary importance in the regulation of placental blood flow, we aimed to clarify the effects of pravastatin on healthy (n = 6) and preeclamptic (n = 6) placentas (Caucasian participants). METHODS: The eNOS activity of human placental microsomes was determined by the conversion rate of C14 L-arginine into C14 L-citrulline with or without pravastatin and Geldanamycin. Phosphorylation of eNOS (Ser1177) was investigated by Western blot. Microsomal arginine uptake was measured by a rapid filtration method. RESULTS: Pravastatin significantly increased total eNOS activity in healthy (28%, p<0.05) and preeclamptic placentas (32%, p<0.05) using 1 mM Ca2+ promoting the dissociation of a eNOS from it's inhibitor caveolin. Pravastatin and Geldanamycin (Hsp90 inhibitor) cotreatment increased microsomal eNOS activity. Pravastatin treatment had no significant effects on Ser1177 phosphorylation of eNOS in either healthy or preeclamptic placentas. Pravastatin induced arginine uptake of placental microsomes in both healthy (38%, p < 0.05) and preeclamptic pregnancies (34%, p < 0.05). CONCLUSIONS: This study provides a novel mechanism of pravastatin action on placental NO metabolism. Pravastatin induces the placental microsomal arginine uptake leading to the rapid activation of eNOS independently of Ser1177 phosphorylation. These new findings may contribute to better understanding of preeclampsia and may also have a clinical relevance.

Analysis of Drosophila melanogaster testis transcriptome.

BACKGROUND: The formation of matured and individual sperm involves a series of molecular and spectacular morphological changes of the developing cysts in Drosophila melanogaster testis. Recent advances in RNA Sequencing (RNA-Seq) technology help us to understand the complexity of eukaryotic transcriptomes by dissecting different tissues and developmental stages of organisms. To gain a better understanding of cellular differentiation of spermatogenesis, we applied RNA-Seq to analyse the testis-specific transcriptome, including coding and non-coding genes. RESULTS: We isolated three different parts of the wild-type testis by dissecting and cutting the different regions: 1.) the apical region, which contains stem cells and developing spermatocytes 2.) the middle region, with enrichment of meiotic cysts 3.) the basal region, which contains elongated post-meiotic cysts with spermatids. Total RNA was isolated from each region and analysed by next-generation sequencing. We collected data from the annotated 17412 Drosophila genes and identified 5381 genes with significant transcript accumulation differences between the regions, representing the main stages of spermatogenesis. We demonstrated for the first time the presence and region specific distribution of 2061 lncRNAs in testis, with 203 significant differences. Using the available modENCODE RNA-Seq data, we determined the tissue specificity indices of Drosophila genes. Combining the indices with our results, we identified genes with region-specific enrichment in testis. CONCLUSION: By multiple analyses of our results and integrating existing knowledge about Drosophila melanogaster spermatogenesis to our dataset, we were able to describe transcript composition of different regions of Drosophila testis, including several stage-specific transcripts. We present searchable visualizations that can facilitate the identification of new components that play role in the organisation and composition of different stages of spermatogenesis, including the less known, but complex regulation of post-meiotic stages.

Early experience with automatic pressure-controlled cerebrospinal fluid drainage during thoracic endovascular aortic repair.

PURPOSE: To report initial experience with automatic pressure-controlled cerebrospinal fluid drainage (CSFD) during thoracic endovascular aortic repair (TEVAR). METHODS: A prospective nonrandomized study enrolled 30 consecutive patients (median age 68 years, range 42-89; 18 men) who underwent TEVAR between March 2012 and July 2013 and were considered to be at high risk for postoperative spinal cord ischemia (SCI), fulfilling 2 of the following criteria: stent-graft length >20 cm, left subclavian artery coverage, and previous infrarenal aortic repair. All patients received perioperative CSFD via the LiquoGuard system. The protocol aimed for a CSF pressure of 10 mm Hg and duration of CSFD of 3 or 7 days in asymptomatic or symptomatic patients, respectively. Muscle strength of the lower extremities was assessed with the Oxford muscle strength grading scale. RESULTS: Completion of the CSFD protocol was achieved in 26 (87%) of 30 patients. CSFD was prematurely stopped due to catheter dislocation in 1 patient and bloody spinal fluid in 3 patients. CSFD was performed for a median of 3 days (range 1-7). Median total CSFD volume was 714 mL (range 13-2369), with a median 192 mL drained per 24 hours. The SCI rate was 3% (1/30). CSFD-related complications were observed in 33% of the patients: 1 fatal intracranial hemorrhage, 3 bloody spinal fluid episodes, 3 persistent CSF leaks requiring epidural blood patch, and 3 post lumbar puncture headaches. Mortality during a median follow-up of 16 months (range 10-25) was 3% (1/30). CONCLUSION: Prophylactic CSFD was associated with a low SCI rate in a high-risk patient collective undergoing TEVAR. Monitoring and drainage by an automatic modus was feasible, reproducible, and reliable but associated with relevant drainage-associated complications.

A meta-analysis on first-trimester blood count parameters-is the neutrophil-to-lymphocyte ratio a potentially novel method for first-trimester preeclampsia screening?

Objective: Meta-analysis focusing on the role of first-trimester neutrophil-to-lymphocyte ratio (NLR) in the prediction of preeclampsia. Data sources: PubMed, Scopus, Web of Science, Cochrane Library, and Embase databases were queried from inception up to December 31, 2022. Study eligibility criteria: The study included all types of original research that was conducted in humans and values of NLR were measured during the first trimester, among patients who later developed preeclampsia, compared to the values of control groups. Study appraisal and synthesis methods: Two reviewers independently performed data abstraction and quality appraisal, and disagreements were resolved by consensus and, if necessary, by the opinion of a third reviewer. During the analysis, PRISMA and MOOSE guidelines were followed. All statistical analyses were made with R. Results: For the research on the predictive role of NLR values in the first trimester for preeclampsia, a total of 6 studies were selected for analysis, covering 2,469 patients. The meta-analysis revealed a 95% confidence interval (CI) for the effect size of 0.641 to 1.523, with a prediction interval of 0.027 to 2.137. Conclusion: Based on the analysis, NLR is a promising biochemical marker for future pieces of research that try to find new screening methods for first-trimester preeclampsia. We encourage other researchers to examine NLR's predictive value combined with other markers in preeclampsia screening, this way being able to find new and affordable protocols for first-trimester preeclampsia screening. Systematic review registration: identifier CRD42023392663.

Ethnic networks in neighborhoods affect mental health: Evidence from a quasi-random assignment of applicants in the public social housing system.

This paper examines the impact of residence-based ethnic networks on mental health; such networks are defined as the concentration of residents from the same country of origin in a neighborhood. To estimate the effect, we utilize administrative registry data, together with data on quasi-random assignment of apartments to non-Western households with housing needs to various neighborhoods. After controlling for individual characteristics, time-invariant neighborhood characteristics, and general practitioners (GP) fixed effects, we find that a 1-percentage-point increase in the concentration of residence-based co-ethnics (RBCEs) increases the probability of being treated with psychiatric medications by 0.7-percentage point over a 5-year period after the assignment. With 19% of the population being treated with psychiatric medications the year before assignment, the result translates into an effect size of 3.7%. The results indicate that relatively high concentrations of co-ethnics treated with psychiatric medications increase the probability of being treated with psychiatric medications. The positive impact on treatment with psychiatric medication reflects an increase in the demand for these drugs when moving into a neighborhood with neighbors of the same ethnicity. If new residents are in good mental health condition when moving, these results suggest that moving into a neighborhood with a high co-ethic concentration worsens mental health status. However, as the population in this study is a vulnerable group an increase in treatment with psychiatric medications likely reflects that untreated mental health problems are treated, and the mental health status improved. The group of non-Western immigrants in this study differs significantly from the population in general, thus, results may not be generalized to all non-Western immigrants.

Meso-scale environmental heterogeneity drives plant trait distributions in fragmented dry grasslands.

Environmental heterogeneity shapes the patterns of resources and limiting factors and therefore can be an important driver of plant community composition through the selection of the most adaptive functional traits. In this study, we explored plant trait-environment relationships in environmentally heterogeneous microsite complexes at the meso-scale (few meters), and used ancient Bulgarian and Hungarian burial mounds covered by dry grasslands as a model habitat. We assessed within-site trait variability typical of certain microsites with different combinations of environmental parameters (mound slopes with different aspects, mound tops, and surrounding plain grasslands) using a dataset of 480 vegetation plots. For this we calculated community-weighted means (CWMs) and abundance models. We found that despite their small size, the vegetation on mounds was characterized by different sets of functional traits (higher canopy, higher level of clonality, and heavier seeds) compared to the plain grasslands. North-facing slopes with mild environmental conditions were characterized by perennial species with light seeds, short flowering period, and a high proportion of dwarf shrubs sharply contrasted from the plain grasslands and from the south-facing slopes and mound tops with harsh environmental conditions. Patterns predicted by CWMs and abundance models differed in the case of certain traits (perenniality, canopy height, and leaf dry matter content), suggesting that environmental factors do not necessarily affect trait optima directly, but influence them indirectly through correlating traits. Due to the large relative differences in environmental parameters, contrasts in trait composition among microsites were mostly consistent and independent from the macroclimate. Mounds with high environmental heterogeneity can considerably increase variability in plant functional traits and ecological strategies at the site and landscape levels. The large trait variation on topographically heterogeneous landscape features can increase community resilience against climate change or stochastic disturbances, which underlines their conservation importance.

A matter of size and shape: Microclimatic changes induced by experimental gap openings in a sessile oak-hornbeam forest.

Forest management integrating nature conservation aspects into timber production focuses increasingly on small-scale interventions. However, the ecological consequences of gap cuttings remain ambiguous in oak-dominated forests. In the Pilis Gap Experiment, we analyze how combinations of different gap shapes (circular and elongated), and gap sizes (150 m2 and 300 m2) affect the microclimate and biota of a mature sessile oak-hornbeam forest in Hungary. We first report the changes in direct and diffuse light, soil moisture, daily air and soil temperatures, and relative air humidity in the experimental cuttings in the vegetation season directly following their implementation. Diffuse light had a central maximum and a concentric pattern. Direct light was distributed along a north-south gradient, with maxima in northern gap parts. Soil moisture was determined by gap shape: it increased significantly in the center of circular gaps, with multiple local maxima in the southern-central parts of large circular gaps. Its pattern was negatively related to direct light, and larger spatial variability was present in circular than in elongated gaps. The daily mean air temperatures at 1.3 m increased in all, especially in large gaps. Soil and ground-level temperatures remained largely unchanged, reflecting on light and soil moisture conditions affecting evaporative cooling. Relative humidity remained unaltered. Even though the opening of experimental gaps changed microclimatic conditions immediately, effect sizes remained moderate. Gap size and gap shape were both important determinants of microclimate responses: gap size markedly affected irradiation increase, gap shape determined soil moisture surplus, while soil and air temperatures, and air humidity depended on both components of the gap design. We conclude that 150-300 m2 sized management-created gaps can essentially maintain forest microclimate while theoretically providing enough light for oak regeneration; and that the manipulation of gap shape and gap size within this range are effective tools of adaptive management.

Anisotropy, Anatomical Region, and Additional Variables Influence Young's Modulus of Bone: A Systematic Review and Meta-Analysis.

The importance of finite element analysis (FEA) is growing in orthopedic research, especially in implant design. However, Young's modulus (E) values, one of the most fundamental parameters, can range across a wide scale. Therefore, our study aimed to identify factors influencing E values in human bone specimens. We report our systematic review and meta-analysis based on the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. We conducted the analysis on November 21, 2021. We included studies investigating healthy human bone specimens and reported on E values regarding demographic data, specimen characteristics, and measurement specifics. In addition, we included study types reporting individual specimen measurements. From the acquired data, we created a cohort in which we performed an exploratory data analysis that included the explanatory variables selected by random forest and regression trees methods, and the comparison of groups using independent samples Welch's t test. A total of 756 entries were included from 48 articles. Eleven different bones of the human body were included in these articles. The range of E values is between 0.008 and 33.7 GPa. The E values were most heavily influenced by the cortical or cancellous type of bone tested. Measuring method (compression, tension, bending, and nanoindentation), the anatomical region within a bone, the position of the bone within the skeleton, and the bone specimen size had a decreasing impact on the E values. Bone anisotropy, specimen condition, patient age, and sex were selected as important variables considering the value of E. On the basis of our results, E values of a bone change with bone characteristics, measurement techniques, and demographic variables. Therefore, the evaluation of FEA should be performed after the standardization of in vitro measurement protocol. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Regeneration in European beech forests after drought: the effects of microclimate, deadwood and browsing.

With progressing climate change, increasing weather extremes will endanger tree regeneration. Canopy openings provide light for tree establishment, but also reduce the microclimatic buffering effect of forests. Thus, disturbances can have both positive and negative impacts on tree regeneration. In 2015, three years before an extreme drought episode hit Central Europe, we established a manipulation experiment with a factorial block design in European beech (Fagus sylvatica L.)-dominated forests. At five sites located in southeastern Germany, we conducted three censuses of tree regeneration after implementing two different canopy disturbances (aggregated and distributed canopy openings), and four deadwood treatments (retaining downed, standing, downed + standing deadwood and removing all deadwood), as well as in one untreated control plot. In addition, we measured understory light levels and recorded local air temperature and humidity over five years. We (i) tested the effects of experimental disturbance and deadwood treatments on regeneration and (ii) identified the drivers of regeneration density as well as seedling species and structural diversity. Regeneration density increased over time. Aggregated canopy openings supported species and structural diversity, but reduced regeneration density. Tree regeneration was positively associated with understory light levels, while maximum vapor pressure deficit influenced tree regeneration negatively. Deadwood and browsing impacts on regeneration varied and were inconclusive. Our study indicates that despite the drought episode regeneration in beech-dominated forests persisted under moderately disturbed canopies. However, the positive effect of increased light availability on tree regeneration might have been offset by harsher microclimate after canopies have been disturbed. Supplementary Information: The online version contains supplementary material available at 10.1007/s10342-022-01520-1.

Genetic identification of members of the prominent Báthory aristocratic family.

The Báthory family was one of the most powerful noble families in the medieval Hungarian Kingdom. Their influence peaked during the Ottoman occupation of Hungary, when the only partially autonomous region of the country was Transylvania, under Turkish protectorate. Several members of the family became Princes of Transylvania, and one of them, István Báthory, was also the elected King of Poland. We hereby present the first genetic data about this extinct family. Archaeological excavations in Pericei, a settlement now part of Romania, revealed the former family chapel of the Báthory family. Through this work, two Báthory family members were successfully identified among the 13 skeletons found at the site. The presence of Y chromosome haplogroup R-S498 fits the historical account describing the family's German (Swabian) origins. Their genomic composition also indicates a family of Germanic origin that intermixed with medieval Hungarians.

Maternal Lineages of Gepids from Transylvania.

According to the written historical sources, the Gepids were a Germanic tribe that settled in the Carpathian Basin during the Migration Period. They were allies of the Huns, and an independent Gepid Kingdom arose after the collapse of the Hun Empire. In this period, the Carpathian Basin was characterized by so-called row-grave cemeteries. Due to the scarcity of historical and archaeological data, we have a poor knowledge of the origin and composition of these barbarian populations, and this is still a subject of debate. To better understand the genetic legacy of migration period societies, we obtained 46 full mitogenome sequences from three Gepid cemeteries located in Transylvania, Romania. The studied samples represent the Classical Gepidic period and illustrate the genetic make-up of this group from the late 5th and early 6th centuries AD, which is characterized by cultural markers associated with the Gepid culture in Transylvania. The genetic structure of the Gepid people is explored for the first time, providing new insights into the genetic makeup of this archaic group. The retrieved genetic data showed mainly the presence of Northwestern European mitochondrial ancient lineages in the Gepid group and all population genetic analyses reiterated the same genetic structure, showing that early ancient mitogenomes from Europe were the major contributors to the Gepid maternal genetic pool.

The genetic legacy of the Hunyadi descendants.

The Hunyadi family is one of the most influential families in the history of Central Europe in the 14th-16th centuries. The family's prestige was established by Johannes Hunyadi, a Turk-beater who rose to the position of governor of the Kingdom of Hungary. His second son, Matthias Hunyadi, became the elected ruler of the Kingdom of Hungary in 1458. The Hunyadi family had unknown origin. Moreover, Matthias failed to found a dynasty because of lacking a legitimate heir and his illegitimate son Johannes Corvinus was unable to obtain the crown. His grandson, Christophorus Corvinus, died in childhood, thus the direct male line of the family ended. In the framework of on interdisciplinary research, we have determined the whole genome sequences of Johannes Corvinus and Christophorus Corvinus by next-generation sequencing technology. Both of them carried the Y-chromosome haplogroup is E1b1b1a1b1a6a1c ∼, which is widespread in Eurasia. The father-son relationship was verified using the classical STR method and whole genome data. Christophorus Corvinus belongs to the rare, sporadically occurring T2c1+146 mitochondrial haplogroup, most frequent around the Mediterranean, while his father belongs to the T2b mitochondrial haplogroup, widespread in Eurasia, both are consistent with the known origin of the mothers. Archaeogenomic analysis indicated that the Corvinus had an ancient European genome composition. Based on the reported genetic data, it will be possible to identify all the other Hunyadi family member, whose only known grave site is known, but who are resting assorted with several other skeletons.

The genetic origin of Huns, Avars, and conquering Hungarians.

Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this "immigrant core" of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the "immigrant core" of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common "proto-Ugric" gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring "native European" ancestry.

Drugs Becoming Generics-The Impact of Genericization on the Market Performance of Antihypertensive Active Pharmaceutical Ingredients.

To explore long-term changes in intra and inter-class choices between generic compounds, this paper investigates the market trends of two antihypertensive drug classes that have closely related pharmacological mechanisms-angiotensin convertase enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We analysed the development of ACEI and ARB markets between 2001 and 2016 in nine European countries, covering the genericization transition periods of both therapeutic groups. The analysis was undertaken on the level of the active pharmaceutical ingredients (API) and focused on international and country-specific diffusion patterns. Comparison of ARB and ACEI therapies shows that although ARBs became off-patent during the observed period, and have a clinical advantage in terms of the adverse event profile over ACEIs, the increasing dominance of ARBs cannot be identified. One explanation is that ACEI therapies became generics earlier, relocating competition to the level of brands, while competition among ARBs remained at the level of the APIs. As for intra-class drug preferences, it was observed that the long-term trends show that ramipril outperformed its ACEI competitors, even though the kinetics and the rank order of preferred active compounds were inconsistent among markets. The diffusion of clinically preferable therapies seems to be ultimately supported by generic entries. In Eastern European countries, the emergence of generic markets has not only improved access to ACE inhibitors and ARBs, but has been a prerequisite for changing preferences. In contrast, genericization resulted in the relative anchoring of prior, branded era-based preferences in some Western European countries, which may be attributed to the role of the cessation of promotion and the fixity of prescription behaviour.

The influence of external load variables on creatine kinase change during preseason training period.

OBJECTIVE: The aim of the present study was to analyse the relationships between creatine kinase (CK) concentration, an indirect marker of muscle damage, and global positioning system (GPS)-derived metrics of a continuous two-week-long preseason training period in elite football. DESIGN: Twenty-one elite male professional soccer players were assessed during a 14-day preseason preparatory period. CK concentrations were determined each morning, and a GPS system was used to quantify the external load. A generalized estimating equation (GEE) model was established to determine the extent to which the external load parameter explained post-training CK levels. RESULTS: The GEE model found that higher numbers of decelerations (χ 2 = 7.83, P = 0.005) were most strongly associated with the post-training CK level. Decelerations and accelerations accounted for 62% and 11% of the post-training CK level, respectively, and considerable interindividual variability existed in the data. CONCLUSION: The use of GPS to predict muscle damage could be of use to coaches and practitioners in prescribing recovery practices. Based on GPS data, more individualized strategies could be devised and could potentially result in better subsequent performance.

Adaptation and Validation of the Food Neophobia Scale: The Case of Hungary.

Food neophobia is the fear or loathing of novel food, which may result in the rejection of the unfamiliar food item. The most frequently used and most reliable tool to measure adult food neophobia is the Food Neophobia Scale (FNS), which has been translated into several languages, making it possible to compare food neophobia levels around the world. The main objective of this research has been the adaptation and validation of the FNS in Hungary. In order to achieve the research objectives, a questionnaire survey was conducted on a representative sample of 500 adults; and, primarily, multivariate statistical tools were used. We found that despite the Hungarian population's strong neophobic tendency, neophobia and neophilia are present at the same time. We identified two distinctive factors in the course of the exploratory factor analysis ("Willingness and trust" and "Rejection and particularity"), which distinctly separate the negatively and positively worded (reversed) FNS items. Based on these factors, four clusters were identified. Those belonging in the group of adventurous open-minded individuals constitute an ideal target group for the manufacturers of novel food items as well as products with unusual flavors, especially if those products also have health-enhancing and eco-friendly qualities.

The Relationship between Online and Offline Information-Seeking Behaviors for Healthy Nutrition.

In addition to preserving their health, young people can also play a role in providing information to wider society. Nutrition habits that have developed over the years at college have an impact on the foundation of a lifelong lifestyle. Our aim was to identify university students' online and offline information-seeking attitudes related to healthy nutrition and create a new theoretical concept. Participants were university students (n = 612), and the self-administered, paper-based questionnaires were sent out to nine Hungarian universities. Both descriptive and multivariate statistical procedures were used in the analysis. Online and offline information sources were categorized. In relation to university students' information-seeking competence, the component of electronic health literacy was determined. In analyzing attitudes, the components of acceptance of, incentive for, and rejection of or ambivalence towards healthy nutrition were identified. The information-seeking categories related to the stages of university students' conscious transition to healthy nutrition were also identified. University students' competences related to electronic health literacy are essentially favorable. This target group accepts healthy nutrition and tries to recommend it to others, too. However, a rejecting or ambivalent attitude could also be identified. Online and offline sources of information accompany university students' transition of the relevant stages of changes. The theoretical concept that we developed can contribute to bridging gaps in the interrelatedness of diverse information sources and healthy nutrition.