Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). ...It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.
Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative ...translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Polycyclic aromatic hydrocarbons (PAHs) are among the most persistent xenobiotic compounds, with high toxicity effects. Mycoremediation with halophilic Aspergillus sydowii was used for their ...removal from a hypersaline medium (1 M NaCl). A. sydowii metabolized PAHs as sole carbon sources, resulting in the removal of up to 90% for both PAHs benzo a pyrene (BaP) and phenanthrene (Phe) after 10 days. Elimination of Phe and BaP was almost exclusively due to biotransformation and not adsorption by dead mycelium and did not correlate with the activity of lignin modifying enzymes (LME). Transcriptomes of A. sydowii grown on PAHs, or on glucose as control, both at hypersaline conditions, revealed 170 upregulated and 76 downregulated genes. Upregulated genes were related to starvation, cell wall remodelling, degradation and metabolism of xenobiotics, DNA/RNA metabolism, energy generation, signalling and general stress responses. Changes of LME expression levels were not detected, while the chloroperoxidase gene, possibly related to detoxification processes in fungi, was strongly upregulated. We propose that two parallel metabolic pathways (mitochondrial and cytosolic) are involved in degradation and detoxification of PAHs in A. sydowii resulting in intracellular oxidation of PAHs. To the best of our knowledge, this is the most comprehensive transcriptomic analysis on fungal degradation of PAHs.
Lactobacilli have been shown to promote health functions. In this study, we analyzed the mechanism by which four different strains of probiotics affected innate immunity, such as regulation of ROS, ...cytokines, phagocytosis, bactericidal activity, signaling by NF-κB pp65, and TLR2 activation. The production of ROS was dependent on the concentration and species of Lactobacillus. The results obtained from the tested strains (Lactobacillus rhamnosus GG, L. rhamnosus KLSD, L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced early proinflammatory cytokines such as IL-8,TNF-α, IL-12p70, and IL-6. However, IL-1β expression was induced only by L. helveticus and L. casei strains (after 24 h stimulation). Phagocytosis and bactericidal activity of macrophages against various pathogens, such as S. aureus, S. typhimurium, and E. coli, were increased by pretreatment with Lactobacillus. The nuclear translocation NF-κB pp65 and TLR2-dependent signaling were also increased by treatment with the probiotics. Taken together, the experiments demonstrate that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages.
A Cu(I)-mediated fluoro-deamination method for nucleophilic radiofluorination was devised. The method affords fluorinated aromatic products directly from anilines under both no-carrier added and ...stoichiometric conditions. Isolated radiochemical yields range from 11% to 81% with high radiochemical purities and a molar activity of 58 MBq/nmol. The reaction conditions were implemented successfully in an automated process for production of (S)-418Ffluorogluthetimide on a radiosynthesis module.
ZnO particles were synthetized by the sol–gel method and subsequent heat treatment of 400, 500 and 600 °C was applied. The nano ZnO particles were incorporated to the unsaturated polyester resin by ...solution blending at 0.05 wt % concentration. X-ray diffraction detected the formation of a wurtzite-like structure. Viscoelastic behavior of neat polyester and nanocomposites revealed the nano ZnO particles does not promote better mechanical properties because of a weak interaction and the glass transition temperature of the polyester was favored by the presence of a higher quantity of nano-size ZnO particles. Thermogravimetric analysis at 5, 10 and 20 °C/min allowed determining the degradation kinetic parameters based on the Friedman and Kissinger models for neat polyester and nanocomposites. Heating rates promoted an increase in the temperature degradation and the addition of ZnO particles promoted a catalyst effect that reduce the amount of thermal energy needed to start the thermal degradation.
Summary
Background
Lactate is an already recognized biomarker for short-term mortality in emergency medical services (EMS). However, how different levels of lactate are associated with short-, mid- ...and long-term outcomes should be unveiled.
Aim
To determine how different categories of hyperlactatemia are associated with mortality. We also aim to clinically characterize hyperlactatemia groups.
Design
A multicenter, prospective, observational study performed between January 2019 and February 2022, considering 48 basic life support units and 5 advanced life support units referring to 4 tertiary care hospitals (Spain). Patients were recruited from phone requests for emergency assistance in adults, evacuated to emergency departments. The primary outcome was in-hospital mortality from any cause within the first to the 365-day period following EMS attendance. The main measures were demographical and biochemical variables, prehospital advanced life support techniques used and patient condition categorized in 24 diseases.
Methods
Univariate and Cox regression analysis.
Results
A total of 5072 participants fulfilled inclusion criteria. Group #1 (non-hyperlactatemia) was composed of 2389 subjects (47.1%), Group #2 (mild hyperlactatemia) of 1834 (36.1%), Group #3 (hyperlactatemia) of 333 (6.6%) and, finally, Group #4 (severe hyperlactatemia) of 516 (10.2%). The 1-day mortality was 0.2%, 1.1%, 9% and 22.3% in the four lactate groups, respectively. Long-term mortality (365 days) was 10.2%, 22.7%, 38.7% and 46.7% in the four lactate groups, respectively. Differences between patients’ conditions of lactatemia groups were also found.
Conclusions
Our results demonstrated that prehospital lactate categories were associated with short- and long-term outcomes in a different manner. These results will allow EMS to establish different risk states according to the prehospital lactate categories.
Mycobacterium chimaera is involved in a worldwide alert due to contaminated heater–cooler units. A real-time polymerase chain reaction (RT-PCR)-based procedure was implemented to survey undetected ...cases of M. chimaera infection. PCR was negative in the 59 prosthetic heart valves from patients with PCR-16SrRNA-negative infective endocarditis. PCR identified M. chimaera in one of 15 clinically significant retrospective Mycobacterium avium–Mycobacterium intracellulare complex isolates, which corresponded to a patient who had undergone heart valve replacement in a different institution. Whole-genome sequencing demonstrated that he was the first case in Spain with involvement of the strain responsible for the global outbreak. These results highlight the relevance of retrospective tracking for undetected M. chimaera infections.
Metformin consumption for diabetes treatment is increasing, leading to its presence in wastewater treatment plants where conventional methods cannot remove it. Therefore, this work aims to analyze ...the performance of advanced oxidation processes using sulfate radicals in the degradation of metformin from water. Experiments were performed in a photoreactor provided with a low-pressure Hg lamp, using K2S2O8 as oxidant and varying the initial metformin concentration (CA0), oxidant concentration (Cox), temperature (T), and pH in a response surface experimental design. The degradation percentages ranged from 26.1 to 87.3%, while the mineralization percentages varied between 15.1 and 64%. Analysis of variance (ANOVA) showed that the output variables were more significantly affected by CA0, Cox, and T. Besides, a reduction of CA0 and an increase of Cox up to 5000 μM maximizes the metformin degradation since the generation of radicals and their interaction with metformin molecules are favored. For the greatest degradation percentage, the first order apparent rate constant achieved was 0.084 min−1. Furthermore, while in acidic pH, temperature benefits metformin degradation, an opposite behavior is obtained in a basic medium because of recombination and inhibition reactions. Moreover, three degradation pathways were suggested based on the six products detected by HPLC-MS: N-cyanoguanidine m/z = 85; N,N-dimethylurea m/z = 89; N,N-dimethyl-cyanamide m/z = 71 N,N-dimethyl-formamide m/z = 74; glicolonitrilo m/z = 58; and guanidine m/z = 60. Finally, it was shown that in general the toxicity of the degradation byproducts was lower than the toxicity of metformin toward Chlamydomonas reinhardtii.