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Despite advances in neonatal care, neonatal jaundice remains a common problem in maternity wards. The present retrospective epidemiological study collected data on a sample of 710 newborns and compared the incidence of neonatal jaundice in infants born to Rh (D) negative and 0 Rh (D) positive mothers. The primary aim was to determine whether the higher incidence of maternal alloimmunisation in newborns was causally related to a potentially higher incidence of neonatal jaundice in newborns of 0 Rh (D) positive mothers. To this end, we investigated a possible association between the incidence of neonatal jaundice in 0 Rh (D) positive mothers and the neonatal blood group. The incidence of neonatal jaundice was not found to differ between maternal blood groups. We discuss new preventive measures that may reduce the incidence of neonatal jaundice and thereby reduce the length of hospital stay.

Invasive plants can interact with soil microbes to enhance their own performance. Such interactive effects may persist and later affect plant performance and their population dynamics. Such ‘invasive soil legacy’ is the specific plant–soil feedback that can affect future invasions, while it is not clear how nitrogen deposition and interspecific competition influence invasive soil legacy. Thus, we collected field soil and conducted a greenhouse experiment to investigate the effects of soil legacy of the invasive tree Rhus typhina on the performance, functional traits and soil microbial communities of R. typhina and the native tree Ailanthus altissima under three nitrogen levels with and without interspecific competition. The experiment revealed that the outcomes of invasive soil legacies were context-specific and depended on local soil nutrient levels and species competition. Specifically, nitrogen addition changed the negative conspecific soil legacy on subsequent R. typhina to a positive effect, while it became negative in A. altissima. The invasive soil legacy promoted the transpirational rate of R. typhina and A. altissima in monoculture, but inhibited it in a mixture under nitrogen deposition. Nitrogen deposition reduced bacteria and fungi biomass of A. altissima in monocultures and mixtures. In contrast, nitrogen deposition decreased bacterial and fungal biomass of R. typhina in monocultures, but enhanced them in mixtures. Therefore, changes in plant growth, transpiration rate and soil microbial biomass might contribute to the different responses of invasive and native plants to invasive soil legacies. Nitrogen deposition and interspecific competition promote the viability of invasive plants from plant–soil feedback and indicate that ranges of subsequent plants might further expand through below-ground process under nitrogen deposition in the future.

Aldo-keto reductases (AKRs), a superfamily of NADP(H)-dependent oxidoreductases, catalyze the oxidoreduction of a wide variety of eobiotic and xenobiotic aldehydes and ketones. In mammals, AKRs play essential roles in hormone and xenobiotic metabolism, oxidative stress, and drug resistance, but little is known about these enzymes in the parasitic nematode Haemonchus contortus. In the present study, 22 AKR genes existing in the H. contortus genome were investigated and a phylogenetic analysis with comparison to AKRs in Caenorhabditis elegans, sheep and humans was conducted. The constitutive transcription levels of all AKRs were measured in eggs, larvae, and adults of H. contortus, and their expression was compared in a drug-sensitive strain (ISE) and a benzimidazole-resistant strain (IRE) previously derived from the sensitive strain by imposing benzimidazole selection pressure. In addition, the inducibility of AKRs by exposure of H. contortus adults to benzimidazole anthelmintic flubendazole in vitro was tested. Phylogenetic analysis demonstrated that the majority of AKR genes in H. contortus lack orthologues in the sheep genome, which is a favorable finding for considering AKRs as potential drug targets. Large differences in the expression levels of individual AKRs were observed, with AKR1, AKR3, AKR8, and AKR10 being the most highly expressed at most developmental stages. Significant changes in the expression of AKRs during the life cycle and pronounced sex differences were found. Comparing the IRE and ISE strains, three AKRs were upregulated, and seven AKRs were downregulated in adults. In addition, the expression of three AKRs was induced by flubendazole exposure in adults of the ISE strain. Based on these results, AKR1, AKR2, AKR3, AKR5, AKR10 and AKR19 in particular merit further investigation and functional characterization with respect to their potential involvement in drug biotransformation and anthelmintic resistance in H. contortus.

Abstract Carbonyl-reducing enzymes (CREs) catalyse the reduction of carbonyl groups in many eobiotic and xenobiotic compounds in all organisms, including helminths. Previous studies have shown the important roles of CREs in the deactivation of several anthelmintic drugs (e.g., flubendazole and mebendazole) in adults infected with the parasitic nematode Haemonchus contortus, in which the activity of a CRE is increased in drug-resistant strains. The aim of the present study was to compare the abilities of nematodes of both a drug-susceptible strain (ISE) and a drug-resistant strain (IRE) to reduce the carbonyl group of flubendazole (FLU) in different developmental stages (eggs, L1/2 larvae, L3 larvae, and adults). In addition, the effects of selected CRE inhibitors (e.g., glycyrrhetinic acid, naringenin, silybin, luteolin, glyceraldehyde, and menadione) on the reduction of FLU were evaluated in vitro and ex vivo in H. contortus adults. The results showed that FLU was reduced by H. contortus in all developmental stages, with adult IRE females being the most metabolically active. Larvae (L1/2 and L3) and adult females of the IRE strain reduced FLU more effectively than those of the ISE strain. Data from the in vitro inhibition study (performed with cytosolic-like fractions of H. contortus adult homogenate) revealed that glycyrrhetinic acid, naringenin, mebendazole and menadione are effective inhibitors of FLU reduction. Ex vivo study data showed that menadione inhibited FLU reduction and also decreased the viability of H. contortus adults to a similar extent. Naringenin and mebendazole were not toxic at the concentrations tested, but they did not inhibit the reduction of FLU in adult worms ex vivo.

Abstract Most drugs used in the treatment of helminthiasis in humans and animals have lost their efficacy due to the development of drug-resistance in helminths. Moreover, since anthelmintics, like many pharmaceuticals, are now recognized as hazardous contaminants of the environment, returning to medicinal plants and their products represents an environmentally friendly way to treat helminthiasis. The goal of the present study was to test the anthelminthic activity of methanol extracts of eight selected European ferns from the genera Dryopteris, Athyrium and Blechnum against the nematode Haemonchus contortus, a widespread parasite of small ruminants. Eggs and adults of H. contortus drug-susceptible strain ISE and drug-resistant strain WR were isolated from experimentally infected sheep. The efficacy of fern extracts was assayed using egg hatch test and adults viability test based on ATP-level measurement. Among the ferns tested, only Dryopteris aemula extract (0.2 mg/mL) inhibited eggs hatching by 25% in comparison to control. Athyrium distentifolium, Dryopteris aemula and Dryopteris cambrensis were effective against H. contortus adults. In concentration 0.1 mg/mL, A. distentifolium, D. aemula, D. cambrensis significantly decreased the viability of females from ISE and WR strains to 36.2%, 51.9%, 32.9% and to 35.3%, 27.0%, 23.3%, respectively in comparison to untreated controls. None of the extracts exhibited toxicity in precise cut slices from ovine liver. Polyphenol’s analysis identified quercetin, kaempferol, luteolin, 3-hydroxybenzoic acid, caffeic acid, coumaric acid and protocatechuic acid as the major components of these anthelmintically active ferns.

Abstract Short-chain dehydrogenases/reductases (SDRs) regulate the activities of many hormones and other signaling molecules and participate in the deactivation of various carbonyl-bearing xenobiotics. Nevertheless, knowledge about these important enzymes in helminths remains limited. The aim of our study was to characterize the SDR superfamily in the parasitic nematode Haemonchus contortus. Genome localization of SDRs was explored, and phylogenetic analysis in comparison with SDRs from free-living nematode Caenorhabditis elegans and the domestic sheep (Ovis aries, a typical host of H. contortus) was constructed. The expression profile of selected SDRs during the life cycle along with differences between the drug-susceptible and drug-resistant strains, were also studied. Genome sequencing enabled the identification of 46 members of the SDR family in H. contortus. A number of genes have no orthologue in the sheep genome. In all developmental stages of H. contortus, SDR1, SDR3, SDR5, SDR6, SDR14, and SDR18 genes were the most expressed, although in individual stages, huge differences in expression levels were observed. A comparison of SDRs expression between the drug-susceptible and drug-resistant strains of H. contortus revealed several SDRs with changed expression in the resistant strain. Specifically, SDR1, SDR12, SDR13, SDR16 are SDR candidates related to drug-resistance, as the expression of these SDRs is consistently increased in most stages of the drug-resistant H. contortus. These findings revealing several SDR enzymes of H. contortus warrant further investigation.

Albendazole (ABZ) is an anthelmintic frequently used to treat haemonchosis, a common parasitosis of ruminants caused by the gastrointestinal nematode Haemonchus contortus. This parasite is able to protect itself against ABZ via the formation of inactive ABZ-glycosides. The present study was designed to deepen the knowledge about the role of UDP-glycosyltransferases (UGTs) in ABZ glycosylation in H. contortus. The induction effect of phenobarbital, a classical inducer of UGTs, as well as ABZ and ABZ-sulphoxide (ABZSO, the main active metabolite of ABZ) on UGTs expression and UGT activity toward ABZ was studied ex vivo in isolated adult nematodes. The effect of three potential UGT inhibitors (5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine and sulfinpyrazone) on ABZ glycosylation was tested. Pre-incubation of nematodes with ABZ and ABZSO led to increased expression of several UGTs as well as ABZ-glycosides formation in subsequent treatment. Phenobarbital also induced UGTs expression, but did not affect ABZ biotransformation. In the nematode's subcellular fraction, sulfinpyrazone inhibited UGT activity toward ABZ, although no effect of other inhibitors was observed. The inhibitory potential of sulfinpyrazone on the formation of ABZ-glycosides was also proved ex vivo in living nematodes. The obtained results confirmed the role of UGTs in ABZ biotransformation in H. contortus adults and revealed sulfinpyrazone as a potent inhibitor of ABZ glycosylation in this parasite. The possible use of sulfinpyrazone with ABZ in combination therapy merits further research.

NKR-P1 is an inhibitory receptor on the surface of natural killer cells, and its engagement with the ligand LLT1 on activated monocytes and B cells triggers NK cell self-tolerance and other immunological processes. Here authors set up a comprehensive, structure-based model of NKR-P1-LLT1 interaction that involves NKR-P1 homodimer formation and subsequent bridging of two LLT1 molecules.

This review article introduces the basic principles of infants’ neurophysiology, while summarizing the core knowledge of the anatomical structure of the auditory pathway, and presents previous findings on newborns’ neural speech processing and suggests their possible applications for clinical practice. In order to tap into the functioning of the auditory pathway in newborns, recent approaches have employed electrophysiological techniques that measure electrical activity of the brain. The neural processing of an incoming auditory stimulus is objectively reflected by means of auditory event-related potentials. The newborn’s nervous system processes the incoming sound, and the associated electrical activity of the brain is measured and extracted as components characterized by amplitude, latency, and polarity. Based on the parameters of event-related potentials, it is possible to assess the maturity of a child’s brain, or to identify a pathology that needs to be treated or mitigated. For instance, in children with a cochlear implant, auditory event-related potentials are employed to evaluate an outcome of the implantation procedure and to monitor the development of hearing. Event-related potentials turn out to be an irreplaceable part of neurodevelopmental care for high-risk children e.g., preterm babies, children with learning disabilities, autism and many other risk factors.

Abstract Soil seed viability and germinability dynamics can have a major influence on the establishment and spread of plants introduced beyond their native distribution range. Yet, we lack information on how temporal variability in these traits could affect the invasion process. To address this issue, we conducted an 8-year seed burial experiment examining seed viability and germinability dynamics for 21 invasive and 38 naturalized herbs in the Czech Republic. Seeds of most naturalized and invasive species persisted in the soil for several years. However, naturalized herbs exhibited greater seed longevity, on average, than invasive ones. Phylogenetic logistic models showed that seed viability (but not germinability) dynamics were significantly related to the invasion status of the study species. Seed viability declined earlier and more sharply in invasive species, and the probability of finding viable seeds of invasive species by the end of the experiment was low. Our findings suggest that invasive herbs might take advantage of high seed viability in the years immediately after dispersal, while naturalized species benefit from extended seed viability over time. These differences, however, are not sufficiently strong to explain the invasiveness of the species examined.

Summary: All plant populations fluctuate in time. Apart from the dynamics imposed by external forces such as climate, these fluctuations can be driven by endogenous processes taking place within the community. In this study, we aimed to identify potential role of soil‐borne microbial communities in driving endogenous fluctuations of plant populations.We combined a unique, 35‐yr long abundance data of 11 common plant species from a species‐rich mountain meadow with development of their soil microbiome (pathogenic fungi, arbuscular mycorrhizal fungi and oomycetes) observed during 4 yr of experimental cultivation in monocultures.Plant species which abundance fluctuated highly in the field (particularly legumes) accumulated plant pathogens in their soil mycobiome. We also identified increasing proportion of mycoparasitic fungi under highly fluctuating legume species, which may indicate an adaptation of these species to mitigate the detrimental effects of pathogens.Our study documented that long‐term fluctuations in the abundance of plant species in grassland communities can be explained by the accumulation of plant pathogens in plant–soil microbiome. By contrast, we found little evidence of the role of mutualists in plant population fluctuations. These findings offer new insights for understanding mechanisms driving both long‐term vegetation dynamics and patterns of species coexistence and richness. [ABSTRACT FROM AUTHOR]

IntroductionA lack of sleep can pose a risk during military operations due to the associated decreases in physical and cognitive performance. However, fast-acting ergogenic aids, such as ammonia inhalants (AI), may temporarily mitigate those adverse effects of total sleep deprivation (TSD). Therefore, the present study aimed to investigate the acute effect of AI on cognitive and physical performance throughout 36 hours of TSD in military personnel.MethodsEighteen male military cadets (24.1 ± 3.0 y; 79.3 ± 8.3 kg) performed 5 identical testing sessions during 36 hours of TSD (after 0 [0], 12 [-12], 24 [-24], and 36 [-36] hours of TSD), and after 8 [+8] hours of recovery sleep. During each testing session, the following assessments were conducted: Epworth sleepiness scale (ESS), simple reaction time (SRT), shooting accuracy (SA), rifle disassembling and reassembling (DAS), and countermovement jump height (JH). Heart rate (HR) was continuously monitored during the SA task, and a rating of perceived exertion (RPE) was obtained during the JH task. At each time point, tests were performed twice, either with AI or without AI as control (CON), in a counterbalanced order.ResultsThere was faster SRT (1.6%; p < 0.01) without increasing the number of errors, higher JH (1.5%; p < 0.01), lower RPE (9.4%; p < 0.001), and higher HR (5.0%; p < 0.001) after using AI compared to CON regardless of TSD. However, neither SA nor DAS were affected by AI or TSD (p > 0.05). Independent of AI, the SRT was slower (3.2-9.3%; p < 0.001) in the mornings (-24, +8) than in the evening (-12), JH was higher (3.0-4.7%, p < 0.001) in the evenings (-12, -36) than in the mornings (0, -24, +8), and RPE was higher (20.0-40.1%; p < 0.001) in the sleep-deprived morning (-24) than all other timepoints (0, -12, -36, +8). Furthermore, higher ESS (59.5-193.4%; p < 0.001) was reported at -24 and -36 than the rest of the time points (0, -12, and + 8).ConclusionAlthough there were detrimental effects of TSD, the usage of AI did not reduce those adverse effects. However, regardless of TSD, AI did result in a short-term increase in HR, improved SRT without affecting the number of errors, and improved JH while concurrently decreasing the RPE. No changes, yet, were observed in SA and DAS. These results suggest that AI could potentially be useful in some military scenarios, regardless of sleep deprivation.

Abstract Haemonchus contortus is a parasitic nematode of ruminants which causes significant losses to many farmers worldwide. Since the drugs currently in use for the treatment of haemonchosis are losing their effectiveness due to the drug-resistance of this nematode, a new or repurposed drug is highly needed. As the antipsychotic drug sertraline (SRT) has been shown to be effective against the parasitic nematodes Trichuris muris, Ancylostoma caninum and Schistosoma mansoni, the aim of the present study was to evaluate the possible effect of SRT on H. contortus. The potential hepatotoxicity of SRT was tested in sheep, a common H. contortus host. In addition, the main metabolic pathways of SRT in H. contortus and the ovine liver were identified. While no effect of SRT on H. contortus egg hatching was observed, SRT was found to significantly decrease the viability of H. contortus adults in drug-sensitive and resistant strains, with its effect comparable to the commonly used anthelmintics levamisole and monepantel. Moreover, SRT in anthelmintically active concentrations showed no toxicity to the ovine liver. Biotransformation of SRT in H. contortus was weak, with most of the drug remaining unmetabolized. Production of the main metabolite hydroxy-SRT did not differ significantly between strains. Other minor metabolites such as SRT-O-glucoside, dihydroxy-SRT, and SRT-ketone were also identified in H. contorts adults. Compared to H. contortus, the ovine liver metabolized SRT more extensively, mainly via desmethylation and glucuronidation. In conclusion, the potency of SRT against H. contortus was proven, and it should be tested further toward possible repurposing.

Introduction: Treatment with orally administered ibandronate is an effective way to increase bone mineral density (BMD) and reduce fracture rate in post-menopausal women and in men with osteoporosis. There are only very few reports concerning ibandronate therapy in children and adolescents, and in patients with osteogenesis imperfecta (OI), as bisphosphonates are not registered for therapeutic use in pediatrics. Case Report: We present three patients with OI, where once-monthly oral ibandronate increased spinal BMD after two and four years, respectively, of therapy without any occurrence of new fractures and no adverse reactions. Somatic growth was not affected by the ibandronate treatment. Conclusion: Once-monthly oral ibandronate increased BMD and most probably improved bone quality in young patients with OI.

Abstract The parasitic gastrointestinal nematode Haemonchus contortus causes serious economic losses to agriculture due to infection and disease in small ruminant livestock. The development of new therapies requires appropriate viability testing, with methods nowadays relying on larval motility or development using procedures that involve microscopy. None of the existing biochemical methods, however, are performed in adults, the target stage of the anthelmintic compounds. Here we present a new test for the viability of H. contortus adults and exsheathed third-stage larvae which is based on a bioluminescent assay of ATP content normalized to total protein concentration measured using bicinchoninic acid. All the procedure steps were optimized to achieve maximal sensitivity and robustness. This novel method can be used as a complementary assay for the phenotypic screening of new compounds with potential antinematode activity in exsheathed third-stage larvae and in adult males. Additionally, it might be used for the detection of drug-resistant isolates.

In areas where forest is under long-term human influence, we can expect that forest bird populations will be affected by changes in forest management. Consequences of such forest management changes can be studied using long-term population trajectories of habitat-defined groups of bird species because various species are associated to different habitat types. Here we focused on 51 species of common forest birds in Czechia, a central European country, using data from a nation-wide breeding bird monitoring scheme collected from 1982 to 2019. Important changes in forest management took place over this time period in Europe and we asked whether the trends in Czech forest bird populations reflected these changes. For this purpose, we defined nine groups according to the species’ habitat associations in respect of stand size, vegetation layers and tree species composition. We calculated annual population indices using log-linear models with Poisson distribution for every species and composed these annual indices into multispecies indicators (MSIs). MSI of all forest birds, as well as MSIs of three groups of habitat generalists showed significant increases over the focal period. The groups of more specialized species showed more variable population trajectories: birds of the shrub layer decreased, whereas birds of the forest canopy and birds of broad-leaved trees increased, and populations of birds of forest edges, forest interior and coniferous trees were stable. These patterns in forest bird populations are consistent with forest maturation and increasing wood volume that took place in Czech forests over several decades. Such changes in forest environment are likely consequences of the change in purposes of forest management from fuel wood to timber harvesting that took place in 20th century resulting in a longer rotation period. Increases in species associated with broad-leaved trees can be explained by replacement of coniferous stands by stands of broad-leaved trees indicating recovery of forest environment towards more natural conditions as majority of the forested area would be naturally covered by broad-leaved vegetation in Czechia. In addition, the occurrence of some broad-leaved trees within coniferous stands, a common practice in Czech forestry, may also provide benefits to populations of bird species associated with broad-leaved trees. Taken together, these results support suitability of current forest management for forest birds that corresponds to recent findings from several other European regions. However, we should take this conclusion with caution because the increases of generalist birds may be also driven by factors outside the forest environment.