A Possible Perspective of Recultivation with Arbuscular Mycorrhiza-Inoculated Drought-Tolerant Herbaceous Plants.

Using native species for urban green space is rather important nowadays. Plant cover on soil is necessary for agronomical and architectural investments as well as conservational programs, which all need minimal maintenance and have to be cost efficient. Commercially available seed mixtures for grasslands and lawns include species that partly originated from other mesoclimatic zones, and thus they may not be able to survive in the long-term, nor will they be adventive to the local ecosystem. With a focus on climate change, the most arid part of the Pannon geographical region was selected (near Törökszentmiklós in Nagykunság, Hungarian Great Plain). The local flora has adapted effectively to the environment; therefore, many species growing there were candidates for this study. Annuals and herbaceous perennials were investigated with respect to harvestability, reproducibility, decorativity, seed production, seed morphological characters (size, mass) and germination features. The selected 20 taxa were inoculated with INOQ Agri mycorrhiza (Rhizophagus irregularis) to increase the drought tolerance and biomass of the plants. Mycorrhizal frequency was significantly different among the taxa, reflecting various responses to the symbiotic interaction and possibly various mycorrhizal dependence of the plant species examined. We did not observe significantly higher colonization rate in most cases of the samples with artificial inoculation treatment. We conclude that the degraded mowed lawn soil that we used could contain propagules of AM fungi in a sufficient amount, so in the artificial grassland restorations, the additional AM inoculation treatment is not necessary to achieve a higher AM colonization rate.

Cost-effectiveness and cost-utility analysis of somatrogon once-weekly injections vs. daily growth hormone injection for treating paediatric growth hormone deficiency in Ireland.

OBJECTIVES: Paediatric growth hormone deficiency (pGHD) manifests as growth failure associated with inadequate growth hormone (GH) production. Daily injections of recombinant human GH (dGH) [somatropin] is the current standard of care, which has been shown to be well tolerated and effective, but associated with suboptimal adherence, leading to reduced effectiveness. Somatrogon, a once-weekly injectable long-acting human GH, has demonstrated clinical non-inferiority and significantly lower life interference (i.e. treatment burden) vs. somatropin in two Phase 3 studies. This work evaluated cost-effectiveness and cost-utility of somatrogon vs dGHs from an Irish payer perspective. METHODS: A Markov model was developed for patients starting somatrogon or dGHs treatment at 3-12 years and continuing up to achievement of near adult height (NAH), with growth driven by trial-based height velocity (HV) and treatment-specific adherence. Patients could discontinue treatment at the end of Year 1 (4%). DGH adherence (95.3%-65% over treatment duration) and adherence-growth relationship were based on published evidence. Higher Year 1 adherence of 4%, tapering over time, for somatrogon vs. dGHs was based on clinical consultation. Treatment costs, monitoring costs and costs due to different wastage types (device setting and adherence) were sourced from local data. Health utilities based on height and injection frequency were derived from published literature. Scenario analysis, deterministic and probabilistic sensitivity analysis were performed. RESULTS: Somatrogon treatment led to 1.87-3.66 cm greater NAH gain and 0.21-0.50 higher quality adjusted life years (QALYs) vs. dGHs, across the base case and scenarios evaluated. Somatrogon treatment was associated with cost savings of €5,699-€21,974 and lower cost per cm gained vs. dGHs (€197-€527), per patient. Somatrogon was cost-effective vs. dGHs, with the result consistent across the sensitivity analyses conducted. CONCLUSION: Somatrogon weekly injections were estimated to result in higher NAH, higher QALYs, lower overall costs and lower costs per cm gained than dGHs, in pGHD.

Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine playing crucial role in immunity. MIF exerts a unique tautomerase enzymatic activity that has relevance concerning its multiple functions and its small molecule inhibitors have been proven to block its pro-inflammatory effects. Here we demonstrate that some of the E-2-arylmethylene-1-tetralones and their heteroanalogues efficiently bind to MIF's active site and inhibit MIF tautomeric (enolase, ketolase activity) functions. A small set of the synthesised derivatives, namely compounds (4), (23), (24), (26) and (32), reduced inflammatory macrophage activation. Two of the selected compounds (24) and (26), however, markedly inhibited ROS and nitrite production, NF-κB activation, TNF-α, IL-6 and CCL-2 cytokine expression. Pre-treatment of mice with compound (24) exaggerated the hypothermic response to high dose of bacterial endotoxin. Our experiments suggest that tetralones and their derivatives inhibit MIF's tautomeric functions and regulate macrophage activation and thermal changes in severe forms of systemic inflammation.

Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia.

Microorganisms or LPS (lipopolysaccharide), an outer membrane component of Gram-negative bacteria, can induce a systemic inflammatory response that leads to sepsis, multiple organ dysfunction, and mortality. Here, we investigated the role of cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT) in the immunosuppressive phase of LPS-induced endotoxic shock. The liver plays an important role in immunity and organ dysfunction; therefore, we used liver RNA sequencing (RNA-seq) data, Ingenuity® Pathway Analysis (IPA ® ) to investigate the complex role of mPT formation in inflammatory reprogramming and disease progression. LPS induced significant changes in the expression of 2844 genes, affecting 179 pathways related to mitochondrial dysfunction, defective oxidative phosphorylation, nitric oxide (NO) and reactive oxygen species (ROS) accumulation, nuclear factor, erythroid 2 like 2 (Nrf2), Toll-like receptors (TLRs), and tumor necrosis factor α receptor (TNFR)-mediated processes in wild-type mice. The disruption of CypD reduced LPS-induced alterations in gene expression and pathways involving TNFRs and TLRs, in addition to improving survival and attenuating oxidative liver damage and the related NO- and ROS-producing pathways. CypD deficiency diminished the suppressive effect of LPS on mitochondrial function, nuclear- and mitochondrial-encoded genes, and mitochondrial DNA (mtDNA) quantity, which could be critical in improving survival. Our data propose that CypD-dependent mPT is an amplifier in inflammatory reprogramming and promotes disease progression. The mortality in human sepsis and shock is associated with mitochondrial dysfunction. Prevention of mPT by CypD disruption reduces inflammatory reprogramming, mitochondrial dysfunction, and lethality; therefore, CypD can be a novel drug target in endotoxic shock and related inflammatory diseases.

Environmental characteristics and taxonomy of microscopic fungi isolated from washing machines.

Washing machines (WMs) are convenient places for fungal colonization. This study is focused on fungal diversity of WMs, and investigates relationships between habits of WM users and colonising species. Housekeeping conditions and habits were assessed in Hungary with a questionnaire. Several fungal species were identified by microscopy and sequence analysis of diagnostic loci. Based on the results, 32 % of the sampled WMs were highly polluted with various species of fungi. Forty six percent of them were colonised also by opportunistically human pathogenic species. In total, 32 yeast and 39 filamentous fungal strains were isolated. Growth tests were conducted with five selected taxa (Cutaneotrichosporon dermatis, Cystobasidium slooffiae, Meyerozyma guilliermondii, Candida parapsilosis and the Fusarium oxysporum species complex (FOSC)) to ascertain their tolerance ranges. None of the examined isolates were able to grow >50 °C, 4.10 < pH < 10.88. FOSC could grow at high salinity. More species were detected in WMs operated in rooms without heating systems (p = 0.0025). The number of species was higher in WMs located in the kitchen than the ones kept in bathroom or in other rooms (p = 0.0205). WMs may serve as a reservoir of pathogenic fungi, the presence of which may depend on the usage of these devices.

Tobacco use among children in Romanian foster care homes.

BACKGROUND: Children living in facilities under the supervision of child protection authorities are vulnerable to early smoking experimentation. This is the first study to report the prevalence and correlates of smoking behaviour among foster care home residents in Romania. METHODS: We conducted an in-person, cross-sectional survey of 914 resident children in 148 foster care homes of four Transylvanian counties. We included children <18 and those with complete tobacco use information in the analytical sample (n = 791). Sociodemographic, peer and foster family characteristics were evaluated for their influence on tobacco experimentation and past 30-day use. RESULTS: Respondents included 50.7% girls of average age 13.6 years (range 8-17). Almost half reported ever experimenting with tobacco (44.6%) and approximately one in four reported past 30-day use (25.9%). Factors significantly associated with an increased odds of smoking experimentation and past 30-day use in the multivariable model included being 13-17 years old (vs. <12 years), having friends who are current smokers, and having a sibling who smokes. Living in a home with a foster mother or foster father who smokes was associated with increased odds of experimentation and past-30 day use, respectively. The longer time living in foster care was associated with decreased odds of experimentation and past 30-day use controlling for all covariates. CONCLUSION: Anti-tobacco programmes that incorporate the role family and peers to reduce smoking are needed to address the high rates of use among Romanian foster care children.

Cyclophilin D disruption attenuates lipopolysaccharide-induced inflammatory response in primary mouse macrophages.

According to recent results, various mitochondrial processes can actively regulate the immune response. In the present report, we studied whether mitochondrial permeability transition (mPT) has such a role. To this end, we compared bacterial lipopolysaccharide (LPS)-induced inflammatory response in cyclophilin D (CypD) knock-out and wild-type mouse resident peritoneal macrophages. CypD is a regulator of mPT; therefore, mPT is damaged in CypD(-/-) cells. We chose this genetic modification-based model because the mPT inhibitor cyclosporine A regulates inflammatory processes by several pathways unrelated to the mitochondria. The LPS increased mitochondrial depolarisation, cellular and mitochondrial reactive oxygen species production, nuclear factor-κB activation, and nitrite- and tumour necrosis factor α accumulation in wild-type cells, but these changes were diminished or absent in the CypD-deficient macrophages. Additionally, LPS enhanced Akt phosphorylation/activation as well as FOXO1 and FOXO3a phosphorylation/inactivation both in wild-type and CypD(-/-) cells. However, Akt and FOXO phosphorylation was significantly more pronounced in CypD-deficient compared to wild-type macrophages. These results provide the first pieces of experimental evidence for the functional regulatory role of mPT in the LPS-induced early inflammatory response of macrophages.

Interocular amplitude and latency differences of pattern ERG and pattern VEP parameters.

PURPOSE: To determine the normal interocular differences in amplitudes and peak times of the pattern electroretinograms (PERGs) and pattern visual evoked potentials (PVEPs) and to investigate whether the PERG and PVEP parameters correspond in lateral dominance or whether the eye-side distributions of the functional parameters are similar. METHODS: The PERGs and PVEPs were recorded in healthy subjects (N = 77) according to the standards of the International Society for Clinical Electrophysiology of Vision, with the modification of the check size of the PERG to 0.5 degrees. This allows stimulation of the macular ganglion cells and their corresponding visual pathways in healthy subjects. RESULTS: Comparison of the averaged higher and lower response amplitudes and the shorter and longer response peak times showed significant differences (p < 0.001) in both the PERG and the PVEP parameters (median [5 to 95%]): the P50 (1.92% [0 to 5.48%]) and N95 (2.06% [0 to 13.95%]) peak times and the P50 (11.82% [1.32 to 29.93%) and N95 (9.45% [1.17 to 30.38%]) amplitudes of the PERGs and the P100 (1.04% [0 to 4.15%]) and N135 (1.96% [0 to 12.36%]) peak times and the P100 (9.86% [1.26 to 29.76%]) and N135 (11.19% [1.18 to 29.99%]) amplitudes of the PVEPs. No significant correlation was found concerning the eye dominance of the PERG and PVEP parameters. CONCLUSIONS: Our results reveal a significant interocular difference on PERG and PVEP recording, but this could not be ascribed to the anatomy of the retina and related visual pathways. If the difference between the eyes is not taken into account, misinterpretation may occur in a pathological process.