SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 μ mol/L=0, K1: 250-450 μ mol/L=4, K2: >450 μ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * diagnosis MeSH
- Atrophy MeSH
- Fibrosis MeSH
- Creatinine MeSH
- Kidney MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Antibodies, Antineutrophil Cytoplasmic * MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
... repetitive DNA in the human genome 46 -- The organization of gene families 47 -- The significance of ... ... affecting how a single gene works: an overview of loss of function and gain of function 218 -- The effect ... ... risk for common genetic diseases and the development of polygenic risk scores 278 -- 8.3 ASPECTS OF ... ... vivo gene therapy 334 -- Viral delivery of therapeutic gene constructs: relatively high efficiency but ... ... the mutational history of cancers: just one of the diverse applications of single-cell genomics and ...
2nd ed. 534 s. : il.
"Genetics and Genomics in Medicine is a new textbook written for undergraduate and graduate students, as well as medical researchers, which explains the science behind the uses of genetics and genomics in medicine today. It is not just about rare inherited and chromosomal disorders, but how genetics affects the whole spectrum of human health and disease. DNA technologies are explained, with emphasis on the modern techniques that have revolutionized the use of genetic information in medicine and are indicating the role of genetics in common complex diseases. The detailed, integrative coverage of genetic approaches to treatment and prevention includes pharmacogenomics and the prospects for personalized medicine. Cancers are essentially genetic diseases and are given a dedicated chapter that includes new insights from cancer genome sequencing. Clinical disorders are covered throughout and there are extensive end-of-chapter questions and problems"--Provided by publisher.
Modern technologies can satisfy human needs only with the use of large quantities of fertilizers and pesticides that are harmful to the environment. For this reason, it is possible to develop new technologies for sustainable agriculture. The process could be carried out by using endophytic microorganisms with a (possible) positive effect on plant vitality. Bacterial endophytes have been reported as plant growth promoters in several kinds of plants under normal and stressful conditions. In this study, isolates of bacterial endophytes from the roots and leaves of Miscanthus giganteus plants were tested for the presence of plant growth-promoting properties and their ability to inhibit pathogens of fungal origin. Selected bacterial isolates were able to solubilize inorganic phosphorus, fix nitrogen, and produce phytohormones, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, and siderophore. Leaf bacterial isolate Pantoea ananat is 50 OL 2 had high production of siderophores (zone ≥ 5 mm), and limited phytohormone production, and was the only one to show ACC deaminase activity. The root bacterial isolate of Pseudomonas libanensis 5 OK 7A showed the best results in phytohormone production (N6-(Δ2-isopentenyl)adenine and indole-3-acetic acid, 11.7 and 12.6 ng·mL-1, respectively). Four fungal cultures-Fusarium sporotrichioides DBM 4330, Sclerotinia sclerotiorum SS-1, Botrytis cinerea DS 90 and Sphaerodes fimicola DS 93-were used to test the antifungal activity of selected bacterial isolates. These fungal cultures represent pathogenic families, especially for crops. All selected root endophyte isolates inhibited the pathogenic growth of all tested fungi with inhibition percentages ranging from 30 to 60%. Antifungal activity was also tested in two forms of immobilization of selected bacterial isolates: one in agar and the other on dextrin-coated cellulose carriers. These results demonstrated that the endophytic Pseudomonas sp. could be used as biofertilizers for crops.
- Publication type
- Journal Article MeSH
Emotional creativity (EC) refers to cognitive abilities and personality traits related to the originality of emotional experience and expression. Previous studies have found that the COVID-19 epidemic and the restrictions imposed increased the levels of negative emotions, which obstructed adaptation. This research suggests that EC predicts the motivation for innovative adaptive behavior under the restrictions of COVID-19. In the case study of university professors, we show that EC predicts the motivation to creatively capitalize on the imposed online teaching in looking for innovative research and personal development. Methodologically, we rely on the Emotional Creativity Inventory (ECI) administered to a sample of 463 university professors (41.5% men, aged 22-100. M ± SD = 45.53 ± 11.46, median 44) from the Czech Republic (N = 137), Slovak Republic (N = 61), and Russia (N = 265). The indicators for motivation for innovative performance included motivations to use distant methods of scientific research, to look for partners for conducting scientific research in other cities or abroad, to conduct interdisciplinary research, starting distance learning to enhance qualifications, and the perception that due to online teaching, there is more time for personal development. We employ a set of ordinal regression analyses controlling for age, gender, position (lecturer, researcher, and manager), type of science (formal, natural, social, and applied), and country. The results suggest that Emotional Creativity and its three components predict the motivation of university professors to creatively capitalize on the imposed online teaching in looking for innovative research and personal development under the conditions of COVID-19. Furthermore, our results confirmed the gender and age differences in EC. The differences in EC according to position (lecturer, researcher, and manager) and type of science were not statistically significant. These results compel us to be aware of the importance of the emotional side of creativity to optimize stress-related behavior under the conditions of limited abilities to continue as usual. More space devoted to the manifestation of all the aspects of emotional creativity would improve adaptation to challenging circumstances and even allow one to capitalize on new opportunities. Moreover, we suggest that if personal intrinsic Emotional Creativity is high, the crises, such as the COVID-19 epidemic, may improve adaptation and trigger creative outcomes.
- Publication type
- Journal Article MeSH
Paulownia tomentosa (Thunb.) Steud is a drought-resistant, low-maintenance and fast-growing energy crop that can withstand a wide range of climatic conditions, provides a high biomass yield (approximately 50 t DM ha-1 yr-1), and develops successfully in contaminated sites. In Kazakhstan, there are many historically contaminated sites polluted by a mixture of xenobiotics of organic and inorganic origin that need to be revitalised. Pilot-scale research evaluated the potential of P. tomentosa for the phytoremediation of soils historically contaminated with organochlorine pesticides (OCPs) and toxic trace elements (TTEs) to minimise their impact on the environment. Targeted soils from the obsolete pesticide stockpiles located in three villages of Talgar district, Almaty region, Kazakhstan, i.e., Amangeldy (soil A), Beskainar (soil B), and Kyzylkairat (soil K), were subjected to research. Twenty OCPs and eight TTEs (As, Cr, Co, Ni, Cu, Zn, Cd, and Pb) were detected in the soils. The phytoremediation potential of P. tomentosa was investigated for OCPs whose concentrations in the soils were significantly different (aldrin, endosulfans, endrin aldehyde, HCB, heptachlor, hexabromobenzene, keltan, methoxychlor, and γ-HCH) and for TTEs (Cu, Zn, and Cd) whose concentrations exceeded maximum permissible concentrations. Bioconcentration (BCF) and translocation (TLF) factors were used as indicators of the phytoremediation process. It was ensured that the uptake and translocation of contaminants by P. tomentosa was highly variable and depended on their properties and concentrations in soil. Besides the ability to bioconcentrate Cr, Ni, and Cu, P. tomentosa demonstrated very encouraging results in the accumulation of endosulfans, keltan, and methoxychlor and the phytoextraction of γ-HCH (TLFs of 1.9-9.9) and HCB (BCFs of 197-571). The results of the pilot trials support the need to further investigate the potential of P. tomentosa for phytoremediation on a field scale.
- Publication type
- Journal Article MeSH
Stomatocystis goerresi sp. n., a gregarine (phylum Apicomplexa, Monocystidae) parasite of an important invasive earthworm in North America, Amynthas tokioensis (Beddard), is described. This is the second species placed into the genus, and details of its morphology and life cycle support Stomatocystis Bandyopadhyay, Mitra et Göçmen, 2006 as a valid taxon. The new species is described using standard nomenclature, measurements, shape descriptors, and photographs of living cells. The parasite was found only in A. tokioensis, and absent in sympatric earthworm species, suggesting it arrived when the earthworms were introduced from their origin from Japan. The species is distinctive from the type species in the genus, S. indica Bandyopadhyay, Mitra et Göçmen, 2006, in being substantially larger in all stages, found in only the host's seminal vesicles, and found in a different host species from East Asia. The distinctive trophozoites/gamonts develop a large funnel structure ringed with a collar of pronounced ridges, and the funnel appears even in the smallest cells. This funnel varies greatly in relative size (to the cell body) and shape, sometimes forming a large fan. The life cycle of S. goerresi is described including distinctive syzygy in which the funnels fuse and then produce a large cell with local centres of isogamete production (thus sex without gender). Gametes are large ( ~5 μm) spheres with complex tips. Oocyst production is large, > 1,000 per mature gametocyst. The genus Stomatocystis is placed into the Monocystidae, but the life cycle of the new species differs from those of other monocystid taxa, which may mean the Monocystidae are not monophyletic or life cycles are variable within the family. Prevalence of S. goerresi at the type locality was high (~ 90%). The parasites destroy the earthworm's organ of sperm self-storage thus eliminating the male function in the hermaphroditic host which may influence the ability of the earthworm to invade and be successful at new sites.
- MeSH
- Apicomplexa classification genetics growth & development isolation & purification MeSH
- Oligochaeta parasitology MeSH
- Life Cycle Stages MeSH
- Introduced Species MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Japan MeSH
Úvod: V současné dynamicky se rozvíjející endodoncii dochází k neustálému vývoji nových postupů ošetření a s tím souvisí i požadavky na kvalitní a spolehlivé materiály potřebné k zaplnění kořenového systému zubu. Před několika lety byly uvedeny na trh nové typy kořenových sealerů na bázi kalciumsilikátových sloučenin, které by mohly splňovat většinu parametrů dokonalého pečeticího materiálu. Novější generace těchto sealerů obsahují příměs kalciumfosfátu a jsou v zahraniční literatuře označovány jako biokeramické sealery. Cílem sdělení je objasnit problematiku této skupiny sealerů a popsat jejich chemické, fyzikální a biologické vlastnosti. Sealery na bázi biokeramických sloučenin mají mnoho společných charakteristik s původním materiálem MTA (mineral trioxide aggregate). Vynikají především hydrofilním profilem a schopností tuhnout ve vlhkém prostředí. V kontaktu s dentinem dochází na jejich povrchu k depozici precipitátů hydroxyapatitu, a tím je potencováno spolehlivé zapečetění kořenového kanálku. Z fyzikálního hlediska jsou objemově stálé a při tuhnutí byla prokázána mírná expanze. Vlhkost prostředí a vysoká afinita k vodě podporují biomineralizační pochody ve tkáních, což spolu s dobrou zatékavostí materiálu umožňuje vyplnit celý prostor kořenového kanálku včetně jeho nepravidelností. Biokompatibilita, schopnost hojení rány a nízká cytotoxicita činí tento typ sealerů vhodný pro trvalý kontakt s tkáněmi periodoncia, kde je prolongovaným uvolňováním vápenatých iontů podporována regenerace. Bylo prokázáno, že díky vysoké hodnotě pH při tuhnutí působí tyto typy sealerů rovněž antimikrobiálně. Pro klinické využití mají dostatečnou rentgen kontrastnost, avšak podle použitého radioopakního aditiva vykazují v různé míře tendenci k dys-koloracím tvrdých zubních tkání. Relativně nevýhodnou vlastností mohou rovněž být zvýšená rozpustnost, porozita a nasákavost vody. Vzhledem k dynamické a bioaktivní povaze těchto sealerů však tyto nepříznivé vlastnosti nemusí být významné pro úspěšnost ošetření v klinické praxi. Mechanické vlastnosti většiny biokeramických sealerů obecně negativně ovlivňuje aplikace tepla, proto jsou pro klinické použití doporučovány kondenzační techniky plnění kořenových kanálků za studena. Závěr: Výstupy klinických a experimentálních studií vyzdvihují výhodné vlastnosti a spolehlivost skupiny sealerů na bázi kalciumsilikátových sloučenin a naznačují do budoucna slibné výsledky při praktickém využití nejen ve specializovaných endodontických praxích.
Introduction: In modern endodontics, there is a constant development of new procedures and requirements for high-quality and reliable materials to fill the root canal system are rising. A few years ago, a new types of calcium silicate-based root canal sealers were launched on the market, which could meet most of the parameters of a perfect sealing material. Newer generations of these sealers contain calcium phosphate and are also referred to in the literature worldwide as bioceramic sealers. Aim of the article: The aim of this article is to present the characteristics of this group of sealers and to outline their chemical, physical and biological properties. Bioceramicbased root canal sealers have many characteristics in common with the original material MTA (mineral trioxide aggregate). They are similar to its chemical composition and setting reaction. They are hydrophilic and able to set in humid environments. In contact with the dentin, hydroxyapatite crystals are deposited on the surface, thus enhancing the sealing ability of the root canal. Considering their physical characteristics, they are volumetrically stable and there is even a slight expansion during material setting. Humidity of the environment and high water sorption promote the biomineralization processes, and contribute to a better seal of the root canal. The flowability of the material allows to fill the entire space of the root canal, even including its irregularities. Biocompatibility, wound healing ability and minimal cytotoxicity make this type of sealer suitable for permanent contact with periodontal tissues, where prolonged release of calcium ions promotes regeneration. High pH value during material setting result in an antimicrobial effect. They have sufficient X-ray contrast for clinical use, but depending on the radiopaque additive used, they show a tendency to discoloration of hard dental tissues. A relatively disadvantageous features are increased solubility, porosity and water absorption. However, due to the dynamic and bioactive nature of these sealers, these adverse properties may not be significant for the success of treatment in clinical practice. The mechanical properties of most bioceramic sealers are generally negatively affected by heat. Due to this fact, cold obturation methods are recommended for bioceramic-based sealers. Conclusion: The outcomes of clinical and experimental studies generally highlight the beneficial properties and reliability of this group of sealers. They suggest promising results not only in specialized endodontic practices.
- Keywords
- biokeramický sealer, kalciumsilikátový sealer,
- MeSH
- Humans MeSH
- Root Canal Filling Materials * MeSH
- Dental Porcelain MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The microaerophilic pathogen Campylobacter jejuni is a leading bacterial cause of human gastroenteritis in developed countries. Even though it has a reputation as a fastidious organism, C. jejuni is widespread and can be easily isolated from various animals, food, and environmental sources. It is suggested that an ability to form biofilms is probably necessary for the survival of C. jejuni under harsh environmental conditions. The first step required for successful biofilm formation is adhesion to a suitable surface. Therefore, in this work, the degree of adhesion was evaluated, followed by characterization and quantification of biofilms using confocal laser scanning microscopy (CLSM). A total of 15 isolates of C. jejuni were used in the experiments (12 isolates from surface and waste waters, 1 human clinical, 1 food and 1 ACTT BAA-2151 collection strain, all samples originated from the Czech Republic). Regardless of the sample origin, all C. jejuni isolates were able to adhere to the polystyrene surface within 30 min, with the number of attached cells increasing with the time of incubation. The resulting data showed that all isolates were able to form complex voluminous biofilms after 24 h of cultivation. The average amount of biovolume ranged from 3.59 × 106 μm3 to 17.50 × 106 μm3 in isolates obtained from different sources of water, 16.79 × 106 μm3 in the food isolate and 10.92 × 106 μm3 in the collection strain. However, the highest amount of biomass was produced by the human clinical isolate (25.48 × 106 μm3). Similar to the quantity, the architecture of the biofilms also differed, from a rugged flat monolayer of cells to large clustered structures. Further, all isolates were tested for the presence of the luxS gene, as the luxS/AI-2 (autoinducer-2) quorum sensing pathway has been previously connected with enhanced biofilm formation. Two isolates originated from surface waters did not possess the luxS gene. These isolates formed thinner and sparser biofilms lacking the presence of significant clusters. However, the ability to adhere to the surface was preserved. The sequencing of the luxS-containing fragments shown a high similarity of the luxS gene among the isolates.
- MeSH
- Bacterial Proteins MeSH
- Biofilms MeSH
- Campylobacter jejuni * genetics MeSH
- Humans MeSH
- Carbon-Sulfur Lyases MeSH
- Quorum Sensing MeSH
- Water MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
The adaptive immune receptors repertoire is highly plastic, with its ability to produce antigen-binding molecules and select those with high affinity for their antigen. Species have developed diverse genetic and structural strategies to create their respective repertoires required for their survival in the different environments. Camelids, until now, considered as a case of evolutionary innovation because of their only heavy-chain antibodies, represent a new mammalian model particularly useful for understanding the role of diversity in the immune system function. Here, we review the structural and functional characteristics and the current status of the genomic organization of camel immunoglobulins (IG) or antibodies, α/ß and γ/δ T cell receptors (TR), and major histocompatibility complex (MHC). In camelid humoral response, in addition to the conventional antibodies, there are IG with "only-heavy-chain" (no light chain, and two identical heavy gamma chains lacking CH1 and with a VH domain designated as VHH). The unique features of these VHH offer advantages in biotechnology and for clinical applications. The TRG and TRD rearranged variable domains of Camelus dromedarius (Arabian camel) display somatic hypermutation (SHM), increasing the intrinsic structural stability in the γ/δ heterodimer and influencing the affinity maturation to a given antigen similar to immunoglobulin genes. The SHM increases the dromedary γ/δ repertoire diversity. In Camelus genus, the general structural organization of the TRB locus is similar to that of the other artiodactyl species, with a pool of TRBV genes positioned at the 5' end of three in tandem D-J-C clusters, followed by a single TRBV gene with an inverted transcriptional orientation located at the 3' end. At the difference of TRG and TRD, the diversity of the TRB variable domains is not shaped by SHM and depends from the classical combinatorial and junctional diversity. The MHC locus is located on chromosome 20 in Camelus dromedarius. Cytogenetic and comparative whole genome analyses revealed the order of the three major regions "Centromere-ClassII-ClassIII-ClassI". Unexpectedly low extent of polymorphisms and haplotypes was observed in all Old World camels despite different geographic origins.
- Publication type
- Journal Article MeSH
- Review MeSH
Nadváha a obezita u dětí jsou spojovány s psychosociálními obtížemi a se znaky psychosomatického onemocnění. V návaznosti na české i zahraniční studie jsme se zabývali tím, zda lze usuzovat na předpojatost vůči českým dětem předškolního věku s nadváhou z projevů sociálního chování a z odhadů výkonů dětí v kognitivních testech (rodiči, učitelkami MŠ). Dvěma souborům předškolních dětí (nadváha; normální tělesná hmotnost; N = 98; 4-6 let) byl předložen Test znalostí předškolních dětí a Urbanův test kreativního myšlení. Rozdíly mezi soubory dětí byly zjištěny v sociálních projevech, výkony dětí v kognitivních testech byly stejné. Z hlediska podmínek našeho výzkumu se předpoklad o významu tělesné hmotnosti pro odhady výkonů dětí ze strany dospělých nepotvrdil. Význam tělesné hmotnosti dětí pro odhad jejich výkonů dospělými se po vstupu např. sociálních proměnných, měnil. Zabývat se otázkami zdravého duševního vývoje dětí s nadváhou je i nadále vhodné, protože souvisejí s možností pozitivních změn v jejich životním stylu i v tělesné hmotnosti.
Objectives. Excess weight and obesity in children are associated with psychosocial complications and have the attributes of psychosomatic illness. The research followed on from Czech and foreign publications about families with overweight and obese children, about the peculiarities of cognitive and social development, and about the psychosocial circumstances that accompany this section of the populace. This paper maps out the existing state of knowledge in the above areas, too.
- MeSH
- Child Behavior * MeSH
- Psychology, Child MeSH
- Child MeSH
- Adult MeSH
- Cognition * MeSH
- Creativity MeSH
- Humans MeSH
- Overweight * MeSH
- Child, Preschool MeSH
- Weight Prejudice statistics & numerical data MeSH
- Surveys and Questionnaires statistics & numerical data MeSH
- Psychological Tests statistics & numerical data MeSH
- Parents psychology MeSH
- Schools, Nursery MeSH
- Social Behavior MeSH
- Psychology, Social MeSH
- Behavior Observation Techniques statistics & numerical data MeSH
- School Teachers psychology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Child, Preschool MeSH