Estimated versus field measured soil gas radon concentration and soil gas permeability.

Prediction of areas with elevated natural radiation is fundamental for the prevention of human exposure. Soil gas radon activity concentration and soil gas permeability are predictive parameters for the radon potential, which has great importance in areas where future urban development is planned. In this study, the soil gas radon equilibrium concentration (C∞) and soil gas permeability (K) were estimated through the application of theoretical and empirical models found in the literature. These models apply soil properties as input parameters. Using already existing soil parameters to predict the radon potential of an area would be useful in avoiding direct field measurements. Therefore, in this study, we examined whether the estimated soil gas radon activity concentration and soil gas permeability values match the values measured in the field. The soil gas radon activity concentration estimated by two theoretical models is about 50% of the measured value in the studied area. This underestimation can be attributed to the assumption that the radon activity concentration measured in the field depends only on soil parameters and the models do not take into account the underlying bedrock. Additionally, these models neglect the radon transport by advection and consider only the radon availability and migration in homogeneous media. Furthermore, they do not count certain characteristics of the soil that can be relevant, e.g. organic matter and clay content in the soil. To investigate more in detail such soil characteristics, seven samples located roughly along the slope, were selected to determine the soil chemical composition by ICP-MS. Evaluating the physical and chemical properties of the soil, it was found that the sampling sites with pH < 8 (low calcium content) the preferential adsorption was a dominant process. This causes radium enrichment in organic matter and clay, which directly influence the soil gas radon activity concentration. At pH > 8, radium is no longer preferentially adsorbed on organic matter but continues to be adsorbed on clays albeit this process is weak because radium competes with calcium cations. Also, there are other factors that may affect radon emanation in soil such as radium concentration and distribution, porosity and water content. In contrast, empirical model of soil gas permeability overestimates the measured value in the study area by an order of magnitude. A new model was made by modifying the previously proposed one, which can be used as a guide for the estimation of the median value of soil gas permeability in granitic areas, but not as an accurate predictor due to the lack of correlation between the estimated and measured values.

The epidemiology of smoking and e-cigarette use in the Hungarian adult population in 2018 / A dohányzás és az e-cigaretta-használat epidemiológiája a felnott magyar népesség körében 2018-ban.

Összefoglaló. Bevezetés: Nagyszámú kutatás igazolta, hogy a dohányzás növeli a legjelentosebb krónikus betegségek kockázatát. Habár 2009 óta csökkeno tendenciát mutat Magyarországon a hagyományos dohányzók aránya, az e-cigarettát kipróbálóké az utóbbi években folyamatosan növekszik. Célkituzés: A 2018-ban a felnott lakosság körében végzett Népegészségügyi Felmérés dohányzásra és e-cigaretta-használatra vonatkozó eredményeinek bemutatása az elozo vizsgálatok tükrében. Módszer: A kérdoíves felmérésben 1586 fo került személyesen lekérdezésre. Az iteratív súlyozás a többlépcsos mintavételi designhatást és a 2016-os mikrocenzus adatait vette figyelembe. Eredmények: 2018-ban a dohányzók aránya a magyar felnott lakosság körében 28,7% (95% MT: 26,3-31,1%), az e-cigarettát használók aránya pedig 1,7% (95% MT: 1,1-2,5%) volt. Az iskolai végzettség a 65 év alattiak esetében a dohányzást befolyásoló tényezo volt (EH: 3,32; 95% MT: 2,53-4,34), de a 65 éves és annál idosebb korcsoportban már nem (EH: 1,11; 95% MT: 0,59-2,09). Az e-cigarettát kipróbálók és használók között a leginkább említett (54,3% 95% MT: 44,0-64,5%) motivációs tényezocsoport a dohányzásról való leszokással, az ártalomcsökkentéssel és a visszaesés megelozésével volt kapcsolatos. A 65 éves és idosebb korcsoportban a dohányzók aránya 2015-höz képest emelkedett. 2018-ban az alapfokú iskolai végzettséguek körében volt a legmagasabb a dohányzók aránya, míg 2014-ben az érettségivel nem rendelkezo középfokú végzettséguek körében. Következtetés: Bár összességében csökkent, az alacsony iskolai végzettséguek és az idosek körében emelkedett a dohányzók aránya Magyarországon. Az e-cigarettát kipróbálók és használók száma növekvo tendenciát mutat hazánkban. Eredményeink az alacsony iskolai végzettséguekre kiemelten fókuszáló, megelozo és leszokást támogató népegészségügyi alprogramokat is tartalmazó komplex beavatkozást sürgetnek. Orv Hetil. 2022; 163(1): 31-38. INTRODUCTION: The body of evidence suggests that smoking increases the risk of the most prevalent chronic diseases. Although the proportion of traditional smokers in Hungary has been on a declining trend since 2009, the proportion of those who tried e-cigarette has been steadily increasing in recent years. OBJECTIVE: To present - in the light of previous studies - the results of the Public Health Survey among adults in 2018 on smoking and e-cigarette use. METHOD: 1586 persons were personally interviewed in a survey. The iterative weighting algorithm considered both the design effect of multistaged sampling and the 2016 Hungarian microcensus. RESULTS: In 2018, the proportion of smokers in the Hungarian adult population was 28.7% (95% CI 26.3-31.1%), and the proportion of e-cigarette users was 1.7% (95% CI 1.1-2.5%). Educational level was a predictor of smoking among respondents younger than 65 years old (OR 3.32; 95% CI 2.53-4.34), but not for those aged 65 years or older (OR 1.11; 95% CI 0.59-2.09). Among e-cigarette ever or current users, the most commonly mentioned (54.3% 95% CI 44.0-64.5%) motivational factor-group to try or use e-cigarettes included motivations to quit smoking, to reduce harm, and to avoid relapsing. In the population aged 65 years old or older, the proportion of smokers increased compared to 2015. The proportion of smokers was the highest among those with primary education in 2018, while in 2014, it was the highest among those with secondary education without a graduation certificate. CONCLUSION: In Hungary, although overall smoking rates are declining, the smoking rate in the low educational group and among the elderly increased. The number of people trying or using e-cigarettes is showing an increasing trend in our country. Our results call for a complex public health intervention program including prevention and smoking cessation supporting subprograms with high focus on those with primary education. Orv Hetil. 2022; 163(1): 31-38.

Vaping-Related Adverse Events and Perceived Health Improvements: A Cross-Sectional Survey among Daily E-Cigarette Users.

Web-based samples of e-cigarette users commonly report significant vaping-related health improvements (HIs) and mild adverse events (AEs). This cross-sectional study with in-person interviewing data collection examined self-reported AEs and perceived HIs among Hungarian adult current daily exclusive e-cigarette (n = 65) and dual users (n = 127), and former daily e-cigarette users (n = 91) in 2018. Logistic regression was used to evaluate associations between reporting any AEs/HIs, vaping status, and covariates. More former users (52.7%) reported AEs than current users (39.6%; p = 0.038). Exclusive and dual daily users reported similar rates of AEs (44.6% and 37.0%, respectively; p = 0.308). More current users (46.9%) experienced HIs than former users (35.2%; p = 0.064). Exclusive daily users were more likely to report HIs than dual users (63.1% versus 38.6%; p = 0.001). Former user status and smoking cessation/reduction reasons increased the odds of reporting AEs, whereas nicotine-containing e-liquid use and older age decreased the odds of reporting AEs. Exclusive vaper status, using advanced generation devices, and smoking cessation/reduction reasons increased the odds of experiencing HIs. This study, which used a traditional data collection methodology, found a higher rate of AEs and a lower rate of HIs compared to web-based surveys. Our results highlight that experiencing AEs and HIs is affected by users' characteristics, in addition to the device and e-liquid type.

Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites.

The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions and that these are reflected in its posttranslational modifications. We found that in post mortem human brain, including in the Substantia nigra, parkin is largely insoluble after age 40 years; this transition is linked to its oxidation, such as at residues Cys95 and Cys253. In mice, oxidative stress induces posttranslational modifications of parkin cysteines that lower its solubility in vivo. Similarly, oxidation of recombinant parkin by hydrogen peroxide (H2O2) promotes its insolubility and aggregate formation, and in exchange leads to the reduction of H2O2. This thiol-based redox activity is diminished by parkin point mutants, e.g., p.C431F and p.G328E. In prkn-null mice, H2O2 levels are increased under oxidative stress conditions, such as acutely by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxin exposure or chronically due to a second, genetic hit; H2O2 levels are also significantly increased in parkin-deficient human brain. In dopamine toxicity studies, wild-type parkin, but not disease-linked mutants, protects human dopaminergic cells, in part through lowering H2O2. Parkin also neutralizes reactive, electrophilic dopamine metabolites via adduct formation, which occurs foremost at the primate-specific residue Cys95. Further, wild-type but not p.C95A-mutant parkin augments melanin formation in vitro. By probing sections of adult, human midbrain from control individuals with epitope-mapped, monoclonal antibodies, we found specific and robust parkin reactivity that co-localizes with neuromelanin pigment, frequently within LAMP-3/CD63+ lysosomes. We conclude that oxidative modifications of parkin cysteines are associated with protective outcomes, which include the reduction of H2O2, conjugation of reactive dopamine metabolites, sequestration of radicals within insoluble aggregates, and increased melanin formation. The loss of these complementary redox effects may augment oxidative stress during ageing in dopamine-producing cells of mutant PRKN allele carriers, thereby enhancing the risk of Parkinson's-linked neurodegeneration.

Modulating α-synuclein fibril formation using DNA tetrahedron nanostructures.

The small presynaptic protein α-synuclein (α-syn) is involved in the etiology of Parkinson's disease owing to its abnormal misfolding. To date, little information is known on the role of DNA nanostructures in the formation of α-syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of α-syn amyloid fibrils were investigated using various biochemical and biophysical methods such as thioflavin T fluorescence assay, atomic force microscopy, light scattering, transmission electron microscopy, and cell-based cytotoxicity assay. It has been shown that DNA tetrahedrons decreased the level of oligomers and increased the level of amyloid fibrils, which corresponded to decreased cellular toxicity. The ability of DNA tetrahedron to facilitate the formation of α-syn amyloid fibrils demonstrated that structured nucleic acids such as DNA tetrahedrons could modulate the process of amyloid fibril formation. Our study suggests that DNA tetrahedrons could be used as an important facilitator toward amyloid fibril formation of α-synuclein, which may be of significance in finding therapeutic approaches to Parkinson's disease and related synucleinopathies.

Structural features of human DJ-1 in distinct Cys106 oxidative states and their relevance to its loss of function in disease.

DJ-1 (PARK7) is a multifunctional protein linked to the onset and progression of a number of diseases, most of which are associated with high oxidative stress. The Cys106 of DJ-1 is unusually reactive and thus sensitive to oxidation, and due to high oxidative stress it was observed to be in various oxidized states in disease condition. The oxidation state of Cys106 of DJ-1 is believed to determine the specific functions of the protein in normal and disease conditions. Here we report molecular dynamics simulation and biophysical experimental studies on DJ-1 in reduced (Cys106, S-), oxidized (Cys106, SO2-), and over-oxidized (Cys106, SO3-) states. To simulate the different oxidation states of Cys106 in DJ-1, AMBER related force field parameters were developed and reported for 3-sulfinoalanine and cysteine sulfonic acid. Our studies found that the overall structure of DJ-1 in different oxidation states was similar globally, while it differed locally significantly, which have implications on its stability, function and its link to disease on-set. Importantly, the results suggest that over-oxidation may trigger loss of functions due to local structural modification in the Cys106 containing pocket of DJ-1 and structurally destabilize the dimeric state of DJ-1, which is believed to be its bioactive conformation. Such loss of functions would result in reduced ability of DJ-1 to protect from oxidative stress insults and may lead to increased progression of disease.

Topological data analysis (TDA) applied to reveal pedogenetic principles of European topsoil system.

Recent developments in applied mathematics are bringing new tools that are capable to synthesize knowledge in various disciplines, and help in finding hidden relationships between variables. One such technique is topological data analysis (TDA), a fusion of classical exploration techniques such as principal component analysis (PCA), and a topological point of view applied to clustering of results. Various phenomena have already received new interpretations thanks to TDA, from the proper choice of sport teams to cancer treatments. For the first time, this technique has been applied in soil science, to show the interaction between physical and chemical soil attributes and main soil-forming factors, such as climate and land use. The topsoil data set of the Land Use/Land Cover Area Frame survey (LUCAS) was used as a comprehensive database that consists of approximately 20,000 samples, each described by 12 physical and chemical parameters. After the application of TDA, results obtained were cross-checked against known grouping parameters including five types of land cover, nine types of climate and the organic carbon content of soil. Some of the grouping characteristics observed using standard approaches were confirmed by TDA (e.g., organic carbon content) but novel subtle relationships (e.g., magnitude of anthropogenic effect in soil formation), were discovered as well. The importance of this finding is that TDA is a unique mathematical technique capable of extracting complex relations hidden in soil science data sets, giving the opportunity to see the influence of physicochemical, biotic and abiotic factors on topsoil formation through fresh eyes.

Baseline Characteristics and Disease Phenotype in Inflammatory Bowel Disease.

OBJECTIVES: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD < 18 years of age were prospectively recorded. RESULTS: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohn's Disease Activity Index [PCDAI] > 31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index > 35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. CONCLUSIONS: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.

Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies.

A potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer's and Parkinson's diseases.

Vector-borne transmission of Besnoitia besnoiti by blood-sucking and secretophagous flies: epidemiological and clinicopathological implications.

BACKGROUND: Bovine besnoitiosis has been recently diagnosed in a three-parted herd of 796 Aubrac and Charolais beef cattle in Hungary. A large scale serological, histological and molecular survey was initiated in order to uncover important factors in the local epidemiology of the disease. FINDINGS: Blood samples were collected (three times from the whole herd, and repeatedly from selected animals) for serological screening by ELISA. In addition, various organs from aborted fetuses and newborn calves, skin and colostrum samples of seropositive heifers/cows, and ticks collected from the cattle were histologically and/or molecularly analysed for the presence of Besnoitia besnoiti. All fetal and calf tissues, as well as colostrum and tick samples from cows were PCR negative. Based on ELISA results, only very few local cows seroconverted after mating with imported, infected bulls, and not necessarily as a consequence of this event. Among calves that were born to seropositive, imported cows and stayed with their mother until weaning at seven months of age, seroprevalence decreased significantly, but remained high. At the same time, 28 calves born from seropositive cows, but separated from their dams immediately after receiving colostrum, were successfully reared and remained uninfected. Following a second herd-level screening, all Aubrac cattle (except for heifer calves) and all seropositive Charolais cows and bulls were culled. Manifestation of the disease is currently sporadic. Among chronically affected heifers two types of skin lesions were noted, and histological evaluation indicated marked distension of sweat gland ducts with membrane-bound structures (resembling cystozoites) in their contents. CONCLUSIONS: Transmission through natural mating, as well as transplacental, colostral and tick-borne transmission of B. besnoiti was either unlikely or did not occur. However, the risk for spreading of the infection was high, when calves stayed with their mother during suckling, and if animals were kept in the same stable (although physically separated) during the main fly season. Herd replacement and generation exchange (i.e. early weaning and artificial feeding) appear to be the successful strategies for the local eradication of bovine besnoitiosis. Adding to the already known mechanical transmission of B. besnoiti by blood-sucking flies, results of the present study suggest that secretophagous flies should also be evaluated as potential vectors of this coccidium species.

Incidence, Paris classification, and follow-up in a nationwide incident cohort of pediatric patients with inflammatory bowel disease.

OBJECTIVES: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. METHODS: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. RESULTS: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105-8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82-5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71-3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22-0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. CONCLUSIONS: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.

Diagnostic yield of upper endoscopy in paediatric patients with Crohn's disease and ulcerative colitis. Subanalysis of the HUPIR registry.

BACKGROUND, AIMS: According to Porto Criteria upper gastrointestinal (UGI) endoscopy is recommended in patients with suspected inflammatory bowel disease (IBD). Nevertheless, previous studies revealed frequent involvement of UGI tract even in patients with ulcerative colitis (UC). The aim of the present study was to determine the diagnostic role of esophagogastroduodenoscopy (EGD) and assess the prevalence and different aspects of UGI involvement in children registered in the Hungarian Pediatric IBD Registry (HUPIR) from 1st of January 2007 to 31th of December 2009. METHODS: Twenty seven institutes provided prospective follow-up data about newly diagnosed IBD patients to HUPIR. The registry was based on detailed questionnaire (76 parameters) involving anamnestic data, laboratory findings, activity indexes, diagnostic procedures, endoscopic examinations (EGD and ileocolonoscopy), and histological data. Localization and phenotype of disease were based on the Montreal classification criteria. RESULTS: During the 3-year period 420 children were diagnosed with IBD, 265 (63%) of them had Crohn's disease (CD), 130 (31%) UC, and 25 (6%) IBD-unclassified (IBD-U). The mean age at diagnosis was 13.2 years (range: 1.2-18 years). EGD was performed in 237 patients (56%), in most cases in patients suffering from CD. Macroscopic lesions on EGD were noted in 64% of patients with CD and 40% of children with UC. Characteristic lesions for CD (ulcer, erosion, aphthous lesion, and granuloma) were noted in 31% of CD patients, however, EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield, 9%). CONCLUSIONS: There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.

Serum ghrelin, adipokine and insulin levels in children with acute hepatitis.

OBJECTIVES: Recent reports suggest that adipokines are potent modulators of inflammation. We tested the hypothesis that the decreased food intake and the acute liver disease might be associated with changes of serum ghrelin, adipokines and insulin levels. METHODS: Fasting ghrelin, adiponectin, leptin, resistin and insulin were measured in 25 children suffering from acute viral hepatitis, caused by either hepatitis A or Epstein-Barr viruses. The age of the patients ranged from 2.2 to 17.2 years (mean: 10.4 years); 10 male and 15 female. Samples for hormones and liver function tests were drawn at 08 : 00 to 09 : 00 h after an overnight fast. The first samples were collected in the morning after the day of admission, the second samples after 2 months of recovery. RESULTS: Ghrelin and adiponectin levels were significantly higher during hepatitis than after recovery (831.4+/-276.44 vs. 736.21+/-274.91 pg/ml, P<0.0001; and 22.91+/-12.93 vs. 15.16+/-8.81 microg/ml, P<0.001, respectively). Adiponectin levels correlated significantly with age-specific and sex-specific body mass index-matched percentile values as well (P=0.0062). Linear regression analysis confirmed that there was a significant association of changes in serum ghrelin and resistin levels and the severity of hepatitis (P=0.005; P<0.05). We could verify a marginal relationship of the changes of serum leptin and the severity of the disease (P=0.0646). CONCLUSION: This study confirms that there are significant changes in serum levels of ghrelin, and adipokines in disease-associated malnutrition and acute hepatitis.

Closing of the flaps of HIV-1 protease induced by substrate binding: a model of a flap closing mechanism in retroviral aspartic proteases.

The active site of aspartic proteases is covered by one or more flaps, which control access to the active site and play a significant role in the binding of the substrate. An extensive conformational change of the flaps takes place upon binding of substrate to the active site. A long molecular dynamics simulation was performed on the complex consisting of a peptide (CA-p2) from a natural substrate cleavage site of the gag/pol polyprotein placed in the active site of HIV-1 protease (PR) with an open flap conformation. During the simulation, the substrate induced the closing of the flaps into the closed conformation in an asymmetrical way through a hydrophobic intermediate state cluster. The nature of the residues of HIV-1 PR identified to be important in the flap closing mechanism is conserved across known structures of retroviral aspartic proteases family. The flap closing mechanism described in HIV-1 PR is proposed to be a general model for flap closing in retroviral aspartic proteases.

Fast protein structure prediction using Monte Carlo simulations with modal moves.

Using normal modes to generate torsion space moves in Monte Carlo simulations of peptides and proteins is not a new idea; nevertheless, despite its power it has not received widespread application. We show that such a "Modal Monte Carlo" approach is an efficient tool for ab initio predictions of small-protein structures. We apply this method to the Trp cage, a 20-residue polypeptide designed to fold rapidly into a structure that includes tertiary contacts, despite its short length. We achieve a high-quality ab initio structure prediction in about 2 orders of magnitude less computation time than state of the art molecular dynamics techniques.