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Despite extensive Salmonella controls used at processing, 5.5% of salmonellosis cases are linked to turkey. This study had two objectives: (i) to summarize USDA-FSIS turkey Salmonella verification program data and (ii) to evaluate Salmonella through turkey production and processing of 22 flocks. In objective 1, USDA-FSIS data show the average Salmonella prevalence in ground turkey from 2016 to 2022 was 15.9%, and that the leading serovar changes frequently. For objective 2, bootsocks (n = 22) were collected on-farm right after load-out. At processing, prescald wingtips (n = 6 composites of 10/flock), prechill wingtips (n = 6 composites of 10/flock), mechanically separated turkey (MST; n = 6 bins/flock), and ground turkey (n = 6 bins/flock) were collected. Salmonella prevalence was determined by a commercial qPCR and culture confirmed. In 33.2% of PCR-positive samples, Salmonella was not confirmed by culture, highlighting a discrepancy between molecular and culture detection. On-farm, 8/22 flocks were Salmonella positive, compared to 21 flocks that were positive at one or more processing locations, including 18 flocks that were positive in at least one final product sample. A logistic regression showed higher Salmonella prevalence in prescald (53.8%) than in prechill (18.2%), MST (27.3%) or ground turkey (26.5%). CRISPR-SeroSeq analysis of 148 culture−positive samples detected 18 Salmonella serovars and showed 35.1% of samples contained multiple serovars. In 16 flocks, one or more serovars detected in final products were absent from any upstream samples. Two−thirds of final product samples containing serovar Typhimurium typed as a live-attenuated Typhimurium vaccine strain. Salmonella on-farm and at prescald did not reflect Salmonella observed in final product. These data underscore the complexity of serovar tracking in turkey production and highlight challenges to identify surveillance samples that accurately represent Salmonella in turkey products.

As communication and trust are both linked with safety, this paper aims to investigate their contribution to aviation maintenance incidents and accidents. For this purpose, the content analysis method is used to investigate whether trust and communication factors were present in aviation maintenance occurrences. Content analysis is used as a qualitative and quantitative tool. For the data analysis, apart from direct investigation for keywords throughout the material for analysis (aviation accident/incident reports with maintenance involvement), a survey tool was also employed. The items of this survey tool (Communication and Trust Question Set) were used to filter the reports’ text to indirectly identify the two factors under examination (communication and trust). As a qualitative tool, the content analysis yielded results via mapping and narrative techniques. As a quantitative tool, results were obtained and reported with the help of descriptive statistics (counts, frequencies). The results indicated that elements of trust and communication are indirectly detectable in aviation maintenance occurrences. Both ineffective communication and lack of trust were identified as a key accident/incident causal condition. Interpersonal trust is recommended to be included in the implementation requirements of any communication system. The limitations associated with the difference in the structure and consistency of the examined material are also discussed.

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells’ susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with – or caused by – ferroptosis.

Members of the Ascarididae family are common zoonotic pathogens in humans and play an economic role in domestic and livestock animal husbandry. This family includes the obligatorily parasitic nematodes of the genus Baylisascaris, with the raccoon roundworm Baylisascaris procyonis being the most well-known representative. B. procyonis uses the raccoon (Procyon lotor) as its primary host and can utilise a broad range of mammals as paratenic hosts. Sexual reproduction of the adult nematodes occurs in the small intestine. Eggs are excreted into the environment through feces, where they develop into the infectious stage under suitable conditions within a few days to weeks. Infection of primary and paratenic hosts occurs through the oral ingestion of these infectious eggs. Raccoons can also become infected by ingesting infected paratenic hosts. Humans serve as accidental hosts and can suffer significant damage to organ tissues, the visual system, and the central nervous system after ingesting infectious eggs. The aim of the study was to investigate the effects of ambient temperature on embryonic development and to document the morphological changes during embryogenesis. Live specimens were collected from the raccoon intestine and incubated. Single-celled eggs were collected during this process. The eggs were decorticated and then preserved. To test the effects of ambient temperature, the eggs were incubated at 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, and 38 °C and monitored at 24-h intervals for their developmental stages. Detailed photographic documentation of the developmental stages was conducted. An increase in ambient temperature led to a reduction in development time. The temperature range within which embryogenesis proceeded to the L1 larval stage was between 10 °C and 30 °C. Incubation at 5 °C did not produce L1 larvae even after 11 months. Incubation at 35 °C and 38 °C resulted in the complete degeneration of the eggs before reaching the L1 larval stage.

Stereotypical behaviour in higher education has been linked with inequality with relevant negative output. This project's aim is to replicate the design of a previous study by expanding further into exploring the gender stereotypes’ relationships for two traditionally gendered polarised areas of study: Engineering and Nursing/Midwifery and assessing participants’ earlier experiences in their secondary education. Survey participants were Engineering and Nursing/Midwifery students (N = 161) of a university in Ireland. Results came positive for stereotypical biases in favour to men in Science, Technology, Engineering and Mathematics (STEM), and specifically for Mathematics. Stereotypes emerged stronger among the female participants. While comparing the two genders within each of the two study areas, significant differences emerge among the female Nursing/Midwifery and female Engineering participants. Female Engineering participants appear with stronger preference, attitude and importance towards STEM than their Nursing/Midwifery counterparts. Nevertheless, Mathematics is an indicator subject for success in higher education and the need to strengthen critical thinking, evidenced based practice and quality of quantitative research in female dominated areas such as Nursing/Midwifery has been recognised. In addition to identified stereotypes, differences in respondents’ views/elements of their interaction with STEM were associated with the type of secondary school they attended. Further research is recommended on traits that could contribute to the formation of gender biased stereotypes in single and mixed gender education systems with an aim to reverse them.

Summary: Peripheral viral infection disrupts oligodendrocyte (OL) homeostasis such that endogenous remyelination may be affected. Here, we demonstrate that influenza A virus infection perpetuated a demyelination- and disease-associated OL phenotype following cuprizone-induced demyelination that resulted in delayed OL maturation and remyelination in the prefrontal cortex. Furthermore, we assessed cellular metabolism ex vivo, and found that infection altered brain OL and microglia metabolism in a manner that opposed the metabolic profile induced by remyelination. Specifically, infection increased glycolytic capacity of OLs and microglia, an effect that was recapitulated by lipopolysaccharide (LPS) stimulation of mixed glia cultures. In contrast, mitochondrial dependence was increased in OLs during remyelination, which was similarly observed in OLs of myelinating P14 mice compared to adult and aged mice. Collectively, our data indicate that respiratory viral infection is capable of suppressing remyelination, and suggest that metabolic dysfunction of OLs is implicated in remyelination impairment.

In this work, for the first time, films were obtained based on biodegradable polyhydroxyalkanoates (PHAs) - a copolymer of 3-hydroxybutyrate-co-3-hydroxyvalerate P(3HB-co-3HV) and a copolymer of 3-hydroxybutyrate-co-4-hydroxybutyrate P(3HB-co-4HB), containing drugs of different chemical structure and action - antibiotics (ceftazidime, doripenem), antiseptic (chlorhexidine) and tissue regeneration stimulator (Actovegin) for drug delivery and cell culture. Using SEM, AFM and measuring the contact angles of water wetting, it is shown how PHAs composition and loading of films of P(3HB-co-3HV) and P(3HB-co-4HB) with drugs affect the porosity, roughness indicators and adhesive properties of the surface. The constructed films are a depot form of drug, the release of which in vitro is realized for a long time, without burst releases, corresponds to Korsmeyer-Peppas and Higuchi models with diffusion character. Films loaded with antibiotics have pronounced antibacterial activity and suppress the development of pathogens S. aureus and E. coli, without a pronounced negative effect on the adhesion and proliferation of epidermal cells. In the cultures of human keratinocytes HaCaT it was shown that the presence of actovegin, as well as ceftazidime in the films, exhibits a stimulating effect, increasing their number. The results demonstrate the suitability of the depot-films for cellular technologies and are promising for the reconstruction of tissues complicated by infection.

To demonstrate predation and potential impacts of raccoons on various species, a total of 108 raccoons from aquatic-associated nature reserves and natural areas in three federal states of Germany, Hesse (n = 36), Saxony-Anhalt (n = 36) and Brandenburg (n = 36), were investigated from a dietary ecological perspective in the present study. Fecal analyses and stomach content examinations were conducted for this purpose. Additionally, as a supplementary method for analyzing the dietary spectrum of raccoons, the parasite fauna was considered, as metazoan parasites, in particular, can serve as indicators for the species and origin of food organisms. While stomach content analyses allow for a detailed recording of trophic relationships solely at the time of sampling, parasitological examinations enable inferences about more distant interaction processes. With their different developmental stages and heteroxenous life cycles involving specific, sometimes obligate, intermediate hosts, they utilize the food web to reach their definitive host. The results of this study clearly demonstrate that spawning areas of amphibians and reptiles were predominantly utilized as food resources by raccoons in the study areas. Thus, common toad (Bufo bufo), common newt (Lissotriton vulgaris), grass frog (Rana temporaria), and grass snake (Natrix natrix) were identified as food organisms for raccoons. The detection of the parasite species Euryhelmis squamula, Isthmiophora melis, and Physocephalus sexalatus with partially high infestation rates also suggests that both amphibians and reptiles belong to the established dietary components of raccoons from an ecological perspective, as amphibians and reptiles are obligate intermediate hosts in the respective parasitic life cycles of the detected parasites. The study clearly demonstrates that raccoons have a significant impact on occurrence-sensitive animal species in certain areas and, as an invasive species, can exert a negative influence on native species and ecosystems.

Cannabis use is common in young adulthood, yet little is known about the prevalence and patterns of multi-modal (i.e., use of more than one mode) cannabis use. Objective: We aimed to (1) determine the past 30-day prevalence of five modes (smoke, vape, edible, dab, other) of cannabis use, (2) describe the prevalence of multi-modal cannabis use (single vs. dual vs. poly-modal), and (3) identify socio-demographic correlates of multi-modal use among young adults. Method: Participants were 764 22–30-year-olds who currently used cannabis from Wave 9 (Spring 2019) of the Marketing and Promotions Across Colleges in Texas Project. Participants were 25.11 years old on average (SD = 1.81), 63.6% female, 38.7% identified as non-Hispanic white, 30.6% as Hispanic/Latino, 13.0% as Asian and 9.4% as Black, and 8.2% identified with two or more races or another race/ethnicity. Bivariate analyses and a multinomial regression were used to examine study questions. Results: Smoking was the most common mode of cannabis use followed by vaping and then edibles. Nearly 43% of participants reported single-modal cannabis use, 33% reported dual-modal use, and 24% reported poly-modal use. Males and those identifying as non-heterosexual were at a greater risk than their counterparts for using multiple modes of cannabis. Participants identifying as Black were at a reduced risk for poly-modal compared to single-modal use. Conclusion: Multi-modal use is common among young adults who currently use cannabis, indicating a need for universal efforts aimed at all young adults. Tailored interventions aimed toward those at elevated risk for multi-modal use also are needed.

Summary: The inflammatory process is associated with oxidative stress and the immune system hyperactivity and is aimed at inducing the restoration of damaged biological structures. However, with prolonged persistence of the immune system hyperactivity, various pathologies can form. The essence of the problem is to bring the immune system hyperactivity back to “normal” after starting the process of restoring damaged structures. On an experimental model of Cu-induced liver fibrosis (Wistar rats), we studied the possibility of eliminating the cellular immunity hyperactivity by oral and intraperitoneal injection of chlorogenic acid (CGA) to animals in comparison with the action of retinol. The effect of retinol or CGA on anatomical and histological changes in the liver, the number of immunocompetent cells (leukocytes, lymphocytes, granulocytes and monocytes), erythrocytes and platelets, and their characteristics in the peripheral blood of rats with Cu-induced fibrosis were determined. It was shown that in animals with liver fibrosis there is hyperactivity of the cellular immunity. The administration of retinol to animals with liver fibrosis three times at a dose of 300 IU/100 g of body weight did not affect to immunocompetent cells number. At the same time the number of erythrocytes in these animals decreased, their volume and anisocytosis increased, i.e. the initial stages of anemia development were manifested. Platelet counts, which were elevated in animals with fibrosis, were restored to normal after retinol addition. At the same time, the administration of CGA per os at the initial stages of the liver fibrosis development was accompanied by a decrease in the cellular immunity hyperactivity (the number of leukocytes, granulocytes decreased to the control level, and the number of monocytes remained somewhat elevated), the number of platelets also decreased to control values, i.e. CGA showed an anti-inflammatory effect. If CGA was injected intraperitoneally, it showed effects similar to retinol. CGA can be used as a biologically active substance that can eliminate the immune system hyperactivity in animals with fibrosis, and it depends on the method of administration CGA into the body.

Originally from Asia, the raccoon dog Nyctereutes procyonoides is an invasive alien species in Europe, listed since 2019 on the List of invasive alien species of Union concern. The raccoon dog is considered to have negative impact on native biodiversity, as well as a crucial role in hosting and transmitting diverse parasites and pathogens of human and veterinary importance. In the present study, stomach content analyses and parasitological examinations were performed on 73 raccoon dogs from Germany. In addition, fecal samples were analyzed. The results of the study confirm the assumption that the examined raccoon dogs were infested with a various ecto- and endoparasite fauna. A total of 9 ecto- and 11 endoparasites were detected, with 6 of the endoparasites having human pathogenic potential. Trichodectes canis (P = 53.42%), Toxocara canis (P = 50.68%) and Uncinaria stenocephala (P = 68.49%) were the most abundant parasite species. The stomach contents consisted of approximately one-third vegetable and two-thirds animal components, composed of various species of amphibians, fish, insects, mammals and birds. Among them were specially protected or endangered species such as the grass frog Rana temporaria. The study shows that the raccoon dog exerts predation pressure on native species due to its omnivorous diet and, as a carrier of various parasites, poses a potential risk of infection to wild, domestic and farm animals and humans.

A comparative study of the effect of drawing and rotary forging on the structure, mechanical and corrosion properties of a new biodegradable magnesium alloy Mg–2Zn–2Ga was carried out. The original 6 mm diameter bars obtained by hot extrusion were reduced to the diameters in the range 5.5–3.3 mm by drawing or rotary forging. Optical microscopy, scanning electron microscopy and EBSD grain orientation mapping were used to characterize the material microstructure. Tensile testing was performed to determine the mechanical properties. The optimum temperature for rotary forging and annealing after each drawing pass for defect-free bar production was found to be 300 °C. The combination of the highest strength and ductility was achieved in the 4.2 mm diameter drawn bar and is explained by the formation of numerous twin boundaries in the alloy structure. The 3.3 mm diameter bar obtained by drawing as well as the 5.5 mm diameter bar obtained by rotary forging showed a balance between high strength (260–310 MPa) and large elongation (9–12 %). The analysis of the stress-strain curves using Hollomon's equation was conducted. The hydrogen evolution test in Hanks' solution revealed that the drawn bars of diameters 4.2 and 5.2 mm, as well as the rotary forged bar of 5.5 mm possessed 3 times lower corrosion resistance reduced in comparison with the original 6 mm extruded bar. The 3.3 mm diameter drawn bar exhibited the lowest nominal corrosion rate of 0.11 mm/year that offers excellent opportunities for use in medical implants.

Duchenne muscular dystrophy (DMD) is a severe hereditary disease caused by a deficiency in the dystrophin protein. The most frequent types of disease-causing mutations in the DMD gene are frameshift deletions of one or more exons. Precision genome editing systems such as CRISPR-Cas9 have shown potential to restore open reading frames in numerous animal studies. Here, we applied an AAV-CRISPR double-cut strategy to correct a mutation in the DMD mouse model with exon 8–34 deletion, encompassing the N-terminal actin-binding domain. We report successful excision of the 100-kb genomic sequence, which includes exons 6 and 7, and partial improvement in cardiorespiratory function. While corrected mRNA was abundant in muscle tissues, only a low level of truncated dystrophin was produced, possibly because of protein instability. Furthermore, CRISPR-Cas9-mediated genome editing upregulated the Dp71f dystrophin isoform on the sarcolemma. Given the previously reported Dp71-associated muscle pathology, our results question the applicability of genome editing strategies for some DMD patients with N-terminal mutations. The safety and efficacy of CRISPR-Cas9 constructs require rigorous investigation in patient-specific animal models.

Purpose: Pediatric brain tumor patients often experience significant cognitive sequelae. Resting-state functional MRI (rsfMRI) provides a measure of brain network organization, and we hypothesize that pediatric brain tumor patients treated with proton therapy will demonstrate abnormal brain network architecture related to cognitive outcome and radiation dosimetry. Participants and Methods: Pediatric brain tumor patients treated with proton therapy were enrolled on a prospective study of cognitive assessment using the NIH Toolbox Cognitive Domain. rsfMRI was obtained in participants able to complete unsedated MRI. Brain system segregation (BSS), a measure of brain network architecture, was calculated for the whole brain, the high-level cognition association systems, and the sensory-motor systems. Results: Twenty-six participants were enrolled in the study for cognitive assessment, and 18 completed rsfMRI. There were baseline cognitive deficits in attention and inhibition and processing speed prior to radiation with worsening performance over time in multiple domains. Average BSS across the whole brain was significantly decreased in participants compared with healthy controls (1.089 and 1.101, respectively; P = 0.001). Average segregation of association systems was significantly lower in participants than in controls (P

The invasive raccoon (Procyon lotor) is an abundant carnivore and considered as an important potential vector of infectious diseases and parasites in Europe. Raccoons show a broad, opportunistic, omnivorous food spectrum. Food supply and habitat quality in urban areas are very attractive for the generalist raccoon. This inevitably leads to increased interaction with humans, domestic animals and livestock, making the raccoon a potentially suitable zoonosis vector. In its autochthonous range, especially in the Eastern and Midwestern United States, the raccoon has been studied very intensively since the beginning of the 20th century. Whereas, basic field biology and parasitology studies in Germany and Europe are lacking and have only been conducted sporadically, regionally and on small sample sizes. In the presented study 234 raccoons from central Germany were comprehensively examined for their metazoan parasite fauna. The present study shows for the first time an extremely diverse parasite fauna in raccoons outside their native range and proves their essential role as intermediate hosts and hosts for ecto- and endoparasites. A total of 23 different parasite species were identified, five of which are human pathogens, 14 of which are new for the parasite fauna of raccoons in Europe. The human pathogenic raccoon roundworm Baylisascaris procyonis is the most common parasite species in this study, with a prevalence of up to 95%. The digenetic trematode Plagiorchis muris, another human pathogenic parasite species, was detected for the first time in raccoons. The ongoing spread of invasive carnivores and the associated spread and transmission of their parasites and other pathogens increases the potential health risk of wild and farmed animals as well as humans. An increase in parasitic diseases in humans (e.g. raccoon roundworm) is to be expected, especially in urban areas, where raccoons are becoming more and more abundant.

Summary: Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios. Additionally, to evaluate model applicability in TWASs, we integrated publicly available multiethnic genome-wide association study (GWAS) summary statistics from the Population Architecture using Genomics and Epidemiology (PAGE) study and Pan-ancestry genetic analysis of the UK Biobank (PanUKBB) with our developed transcriptome prediction models. In regard to transcriptome prediction accuracy, MASHR models performed better or the same as other methods in both population-matched and cross-population transcriptome predictions. Furthermore, in multiethnic TWASs, MASHR models yielded more discoveries that replicate in both PAGE and PanUKBB across all methods analyzed, including loci previously mapped in GWASs and loci previously not found in GWASs. Overall, our study demonstrates the importance of using methods that benefit from different populations’ effect size estimates in order to improve TWASs for multiethnic or underrepresented populations.

Porous NiTi samples were obtained by self-propagating high-temperature synthesis (SHS) and cut to specific dimensions by electrical discharge machining. Quasi-static compression of the porous SHS-NiTi alloy demonstrated that the deformation was elastic-plastic. Three characteristic types of fracture surfaces of bridges can be distinguished. 1) Ductile fracture of the austenite phase in the form of a cup and cone relief. 2) Brittle fracture with the formation of cleavage steps. 3) Large areas of plastic shear, where cup and cone, and cleavage facets are nucleated. An algorithm for obtaining a porous framework model suitable for finite element method calculations has been developed. The effective moduli of elasticity and shear for the porous volume of the material were determined. It is shown that the studied porous volume has orthotropic elastic properties due to the geometry of the porous framework.

Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional CVD risk factors cannot completely explain the increased risk. Altered HDL proteome is linked with incident CVD in CKD patients, but it is unclear whether other HDL metrics are associated with incident CVD in this population. In the current study, we analyzed samples from two independent prospective case-control cohorts of CKD patients, the Clinical Phenotyping and Resource Biobank Core (CPROBE) and the Chronic Renal Insufficiency Cohort (CRIC). We measured HDL particle sizes and concentrations (HDL-P) by calibrated ion mobility analysis and HDL cholesterol efflux capacity (CEC) by cAMP-stimulated J774 macrophages in 92 subjects from the CPROBE cohort (46 CVD and 46 controls) and in 91 subjects from the CRIC cohort (34 CVD and 57 controls). We tested associations of HDL metrics with incident CVD using logistic regression analysis. No significant associations were found for HDL-C or HDL-CEC in either cohort. Total HDL-P was only negatively associated with incident CVD in the CRIC cohort in unadjusted analysis. Among the six sized HDL subspecies, only medium-sized HDL-P was significantly and negatively associated with incident CVD in both cohorts after adjusting for clinical confounders and lipid risk factors with odds ratios (per 1-SD) of 0.45 (0.22–0.93, P = 0.032) and 0.42 (0.20–0.87, P = 0.019) for CPROBE and CRIC cohorts, respectively. Our observations indicate that medium-sized HDL-P—but not other-sized HDL-P or total HDL-P, HDL-C, or HDL-CEC—may be a prognostic cardiovascular risk marker in CKD.

The COVID-19 pandemic provides both reasons to quit smoking as well as stress that may promote increased cigarette consumption. Perceptions of COVID-19 risk related to smoking may motivate cessation among smokers. At the same time, other evidence shows that affective perceptions (i.e., worry) could lead to increased smoking as a coping mechanism. Using a sample drawn from a rural region of California (N = 295), we examined the relationship between perceptions about health risks for smokers during the pandemic and both reported increases in smoking frequency and intentions to quit smoking. We also examined whether worry about health risks mediated these relationships. High perceived risk was associated both with reported increases in smoking frequency as well as greater intentions to quit smoking. Worry partially mediated both these relationships, with worry accounting for 29.11% of the variance in the relationship between high risk perceptions and increased smoking as well as 20.17% of the relationship between risk perceptions and intentions to quit smoking. These findings suggest that while smokers’ awareness about their increased risk of COVID-19 can motivate intent to quit smoking in the future, smokers may require greater support to act on these intentions.

In this study, a novel hydrodynamic cavitation unit combined with a glow plasma discharge system (HC-GPD) was proposed for the degradation of pharmaceutical compounds in drinking water. Metronidazole (MNZ), a commonly used broad-spectrum antibiotic, was selected to demonstrate the potential of the proposed system. Cavitation bubbles generated by hydrodynamic cavitation (HC) can provide a pathway for charge conduction during glow plasma discharge (GPD). The synergistic effect between HC and GPD promotes the production of hydroxyl radicals, emission of UV light, and shock waves for MNZ degradation. Sonochemical dosimetry provided information on the enhanced formation of hydroxyl radicals during glow plasma discharge compared to hydrodynamic cavitation alone. Experimental results showed a MNZ degradation of 14% in 15 min for the HC alone (solution initially containing 300 × 10−6 mol L−1 MNZ). In experiments with the HC-GPD system, MNZ degradation of 90% in 15 min was detected. No significant differences were observed in MNZ degradation in acidic and alkaline solutions. MNZ degradation was also studied in the presence of inorganic anions. Experimental results showed that the system is suitable for the treatment of solutions with conductivity up to 1500 × 10−6 S cm−1. The results of sonochemical dosimetry showed the formation of oxidant species of 0.15 × 10−3 mol H2O2 L−1 in the HC system after 15 min. For the HC-GPD system, the concentration of oxidant species after 15 min reached 13 × 10−3 mol H2O2 L−1. Based on these results, the potential of combining HC and GPD systems for water treatment was demonstrated. The present work provided useful information on the synergistic effect between hydrodynamic cavitation and glow plasma discharge and their application for the degradation of antibiotics in drinking water.

Background: Spatial ability (SA) shows wide variability. One proposed explanation for the observed individual difference in SA is variability in interest and engagement in activities that promote spatial ability. Research also robustly shown that males on average outperform females in most aspects of SA. Previous studies have identified a number of activities that can potentially contribute to both individual and gender differences in SA, including tinkering with electronics, particular sports activities, and designing. However, the findings regarding these links are inconsistent. One way to investigate these links is to compare the groups that are intensively engaged with these activities. Aim: The present study aims to evaluate the robustness of these links by comparing SA in adolescents with expertise in STEM, arts, and sports, with their unselected peers. We also aimed to assess whether gender differences in SA are still present in expert groups. Methods: The data on ten small-scale SA tests was collected in an unselected sample of adolescents (N = 864, Mean age = 15.4, SD = 1.1); as well as in 3 samples of adolescents with expertise in STEM (N = 667, Mean age = 15, SD = 1.2); in Arts (N = 280, Mean age = 15, SD = 1.2) and in Sports (N = 444, Mean age = 14.3, SD = 0.7). Results: Out of the three expert groups, only STEM experts on average outperformed the unselected group on all SA tasks. The STEM experts also outperformed Arts and Sports experts. Gender differences persisted in all expert groups, with moderate effect sizes. Discussion: Findings support previously established links between spatial ability and STEM-related expertise. In contrast, such links were not found for expertise in arts and sports. Consistent with previous research, we found gender differences in SA for all samples, which persisted in STEM experts.

Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD–reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD–reared groups were examined using regression modeling, controlling for sex, weight, and age. Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

The soil response to a jet-fuel contamination is uncertain. In this article, original data on the influence of a jet-fuel spillage on the topsoil properties are presented. The data set is obtained during a one-year long pot and field experiments with Dystric Arenosols, Fibric Histosols and Albic Luvisols. Kerosene loads were 1, 5, 10, 25 and 100 g/kg. The data set includes information about temporal changes in kerosene concentration; physicochemical properties, such as рН, moisture, cation exchange capacity, content of soil organic matter, available P and K, exchangeable NH4+, and water-soluble NO3–; and biological properties, such as biological consumption of oxygen, and cellulolytic activity. Also, we provide sequencing data on variable regions of 16S ribosomal RNA of microbial communities from the respective soil samples.

The liver fluke Opisthorchis felineus is a clinically important food-borne parasite of humans. Infection with O. felineus in mammals is associated with liver morbidities such as periductal fibrosis, bile duct neoplasia, and chronic inflammation. Previously we have shown that excretory-secretory products (ESP) can stimulate the healing of skin wounds in mice, which may be due to stimulated angiogenesis and extracellular matrix remodeling. However, there are no studies analyzing the angiogenic character of O. felineus, and its effects on angiogenesis, vascularity, and vascular endothelium. The aim of this study was to evaluate the capacity of ESP and extracellular vesicles (EVs) of O. felineus to stimulate angiogenesis and the formation of pseudo-capillaries in vitro. We also aimed at the assessment of the angiogenesis during the infection in vivo, and estimation of the endothelial cell type abundances from heterogeneous bulk liver transcriptome between uninfected and infected animals with single-cell information. The study revealed significant alterations in vascularity in the hamster liver and significant involvement of portal endothelial cells at the transcriptome level. We also demonstrated that the ESP and EVs of O. felineus have the capacity to stimulate the formation of pseudo-capillaries in vitro. Both ESP and EVs appeared to have similar effects on all four parameters, increasing node formation and total master segments length, and significantly decreasing total isolated branches length and number of isolated segments of pseudo-capillaries. The liver flukes manipulate the hostʼs angiogenic response, a fact that has been related to the pathogenesis caused by these parasites. Understanding these pathogenic mechanisms may uncover new therapeutic targets to relieve or prevent the most severe complications of opisthorchiasis.

As a person who has had a long scientific career in Ukraine, both before and after its re-acquisition of independence thirty years ago, I would like to share my observations with the readership of this Special Issue. By no means are these observations meant to provide a systematic presentation, which requires a different format. Rather, they are highly personal notes, providing snippets of the past and present and a discussion of the future of Ukrainian science. They also allow me to acknowledge my wonderful colleagues and bright students. I am delighted to see that many of them have contributed excellent reviews and original manuscripts to this Special Issue. (I am also keenly aware of the fact that because of the brutal invasion and bombardments by our imperial neighbor, many of my colleagues have been unable to share their latest work). It will be up to this next generation of Ukrainian scientists to develop Biological Sciences in Ukraine in the future.

Objective: There is minimal research that has measured motivations behind e-cigarette use and the relationship to cigarette and e-cigarette use. The aim of this study was to (1) examine extent to which motivations to use e-cigarettes varies among dual users and (2) examine whether e-cigarette motivations are related to e-cigarette and cigarette consumption among dual users. Methods: Adults residing in California were recruited through social media (n = 1762, 68.9 % males, 62.9 % White) to complete an online survey. Participants self-identified as using combustible cigarettes and e-cigarettes (dual users) and reported their motivations for using an e-cigarette device, nicotine consumption, and nicotine dependence with both combustible cigarettes and e-cigarettes. Results: A greater proportion of people reported using e-cigarettes for enjoyment purposes than other motivations (34.2 %). Motivations to use e-cigarettes to quit were positively related to monthly cigarette consumption (IRR = 1.17, 95 % CI [1.08, 1.26]). Motivations to use e-cigarettes to quit smoking were also related to smoking the first cigarette within 30 min (IRR = 1.46, 95 % CI [1.05, 2.02]) and first e-cigarette within 30 min (b = 0.28, 95 % CI [0.19, 0.37]). Conclusions: Compared to those who use e-cigarettes for enjoyment, smokers who are motivated to use e-cigarettes for cessation purposes are more likely to have greater nicotine dependence, cigarette consumption, and e-cigarette consumption. Future research needs to acknowledge that not all e-cigarette users are the same; motivations and use differ and are related to both consumption and dependence.

Summary: The social ameba Dictyostelium discoideum has emerged as a powerful model to study mitochondrial genetics and bioenergetics. However, a comprehensive inventory of mitochondrial proteins that is critical to understanding mitochondrial processes has yet to be curated. Here, we utilized high-throughput multiplexed protein quantitation and homology analyses to generate a high-confidence mitochondrial protein compendium consisting of 936 proteins. Our proteomic approach, which utilizes mass spectrometry in combination with mathematical modeling, was validated through mitochondrial targeting sequence prediction and live-cell imaging. Our final compendium consists of 936 proteins. Nearly, a third of D. discoideum mitochondrial proteins do not have homologs in humans, budding yeasts, or an ancestral alphaproteobacteria. Additionally, we leverage our compendium to highlight the complexity of metabolic reprogramming during starvation-induced development. Our compendium lays a foundation to investigate mitochondrial processes that are unique in ameba and to understand the functions of conserved mitochondrial proteins in D. discoideum.

Surgical correction of abdominal muscle diastasis may decrease intra-abdominal volume and increase intra-abdominal pressure. The induced changes may ultimately lead to respiratory compromise. In abdominoplasty, one of the most frequently performed esthetic procedures, those changes are believed to be transient and clinically insignificant. We describe a case where acute change in respiratory physiology after abdominoplasty led to severe respiratory failure with significantly decreased pulmonary compliance in a young and otherwise healthy patient. In this case mechanical ventilation failed to improve compliance, and reversal of abdominoplasty was required to restitute pulmonary function.

Gender stereotypes are identified as a significant contributor to persistent inequality and in an educational arena, it has far reaching effects. As third level students select their area of study, their stereotypes can influence the degree of integration or exclusion in a particular area of study. Over the years, this has resulted to multiple research studies in the investigation of gender stereotypes with particular emphasis in the relationship between gender stereotypes and selected areas of study (Sciences and Liberal Arts) among men and women. In this study the implicit stereotypes of participants were targeted as they are indicative of their delicate mental associations. A quantitative survey was conducted to investigate the extent of gender-area of study stereotypes among Irish third level students. Results indicated that participants felt that, even though both genders devote time to their work equally, it is men that spend more time away from their families, are frequent achievers of high levels on performance and show more natural interest in Science, Technology, Engineering or Maths. Especially among female participants, males scored higher as high achievers in Mathematics and were declared to have more ‘natural’ interest in Science. Comparison between this study and another international big scale study was deemed reliable and comparable.

The article presents protocols for determining the biological activity of kerosene-contaminated soils in terms of two indicators, i.e. cellulolytic activity and biological consumption of oxygen. A method for determining the cellulolytic activity of soils is based on measuring the rate of cellulose decomposition in situ. Model test objects (linen fragments 10 × 20 cm weighing 4–6 g) were put in the root layer of soil. A month later, the linen was removed from soil and its weight loss was measured. Cellulolytic activity was estimated by the weight loss of readily hydrolysable organic matter (RHOM) per day (mg/g RHOM per day). The method for determining the biological consumption of oxygen of water was adapted for soils. The indicator characterizes the ability of microorganisms to oxidize organic substances using oxygen for 5 days. The analytic procedure includes taking a soil sample, preparing the suspension (the ratio of soil to distilled water is at least 1:10) and after 5 days measuring the concentration of unspent dissolved oxygen using the oxygen meter. The proposed methods give reproducible and reliable results on the biochemical activity of soil microorganisms in a wide range of soils, e.g. Retisols, Arenosols and Histosols, including those under hydrocarbon pollution.

Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by an evident shortage in the supply of licensed vaccines. In an effort to satisfy vaccine demands we developed a new single-dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein – “Sputnik Light”. Methods: We conducted an open label, prospective, non-randomised phase 1/2 trial aimed to assess safety, tolerability, and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-CoV-2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). Findings: Most of the solicited adverse reactions were mild (66·4% from all vaccinees), few were moderate (5·5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-CoV-2 antibodies revealed a group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data based on pre-existing immunity to SARS-CoV-2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (​GMT) 594·4 at a baseline up to 26899 comparing to 29·09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time, in the seropositive group, seroconversion rate by day 42 was 92·9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81·7% (76/93) and 92·9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15·18 and 579·7 in the seronegative and seropositive groups, respectively. Antigen-specific T cell proliferation, formation of IFNy-producing cells, and IFNy secretion were observed in 96·7% (26/27), 96% (24/25), and 96% (24/25) of the seronegative group respectively and in 100% (3/3), 100% (5/5), and 100% (5/5) of the seropositive vaccinees, respectively. Interpretation: The single-dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induces a strong humoral and cellular immune responses both in seronegative and seropositive participants. Funding: Russian Direct Investment Fund.

The search for the ways of thermal stabilization of supported metal catalysts is an important challenge in the modern catalysis. Chemical modification of support seems to be the most versatile approach to stabilize the metal particles against sintering and alter their catalytic performance. Also for such modification nitrogen doping can be used and is considered rather perspective. In a recent manuscript (A.M. Dmitrachkov, R.I. Kvon, A.V. Nartova, N-doping of alumina thin film support to improve the thermal stability of catalysts: preparation and investigation, Appl. Surf. Sci.) we have developed the procedure of N-doping of alumina thin film grown at the surface of metal substrate. Proposed N-doped model alumina support is suitable for catalysis – oriented surface science studies and improves the resistance of supported metal particles against thermal driven sintering. Herein, we provide useful complementary data for the characterization of the prepared materials in the form of:in situ / ex situ XPS (X-ray photoelectron spectroscopy) spectra at every stage of sample preparation, including angle resolved XPS experiments and thermal stability tests;STM (scanning tunneling microscopy) images of supported gold catalysts. Presented data support the proposed mechanism of film formation and modification.

Antibiotic residues in water are general health and environmental risks due to the antibiotic-resistance phenomenon. Sonication has been included among the advanced oxidation processes (AOPs) used to remove recalcitrant contaminants in aquatic environments. Sonochemical processes have shown substantial advantages, including cleanliness, safety, energy savings and either negligible or no secondary pollution. This review provides a wide overview of the different protocols and degradation mechanisms for antibiotics that either use sonication alone or in hybrid processes, such as sonication with catalysts, Fenton and Fenton-like processes, photolysis, ozonation, etc.

Family history of metabolic conditions is a primary factor for clinicians to consider when administering preventive care. Sharing this information with healthcare providers proactively is therefore important to individual health outcomes. This brief report seeks to identify factors associated with sharing family history with healthcare providers in individuals of Mexican heritage. Data were obtained from a health education intervention study conducted during 2008–2010, which recruited 497 adult participants from 162 multigenerational households in Houston, Texas to receive family history-based risk feedback generated by Family Healthware™. Households were randomized to receive a pedigree of metabolic conditions or a pedigree coupled with supplementary information about one’s personalized risk assessment and behavioral recommendations. Participants completed two follow-up surveys at three and ten months post intervention, respectively. Analysis based on 296 participants from 147 households who read but did not share their feedback at three-month follow-up suggests benefits of providing personalized risk assessment and tailored behavioral recommendations in addition to a simple pedigree. Participants receiving supplementary risk feedback are more likely to share it with family members at three-month follow-up, which is associated with increased sharing and willingness to share risk feedback with healthcare providers at ten-month follow-up. The findings highlight the importance of family relationships in medical information disclosure in Mexican American adults. Future interventions should capitalize on family relationships in health education and promotion programs for optimal prevention of metabolic conditions in at-risk populations.

Background: It is increasingly evident that perturbations to the diversity and composition of the gut microbiota have significant consequences for the regulation of integrative physiological systems. There is growing interest in the potential contribution of microbiota-gut-brain signalling to cardiorespiratory control in health and disease. Methods: In adult male rats, we sought to determine the cardiorespiratory effects of manipulation of the gut microbiota following a 4-week administration of a cocktail of antibiotics. We subsequently explored the effects of administration of faecal microbiota from pooled control (vehicle) rat faeces, given by gavage to vehicle- and antibiotic-treated rats. Findings: Antibiotic intervention depressed the ventilatory response to hypercapnic stress in conscious animals, owing to a reduction in the respiratory frequency response to carbon dioxide. Baseline frequency, respiratory timing variability, and the expression of apnoeas and sighs were normal. Microbiota-depleted rats had decreased systolic blood pressure. Faecal microbiota transfer to vehicle- and antibiotic-treated animals also disrupted the gut microbiota composition, associated with depressed ventilatory responsiveness to hypercapnia. Chronic antibiotic intervention or faecal microbiota transfer both caused significant disruptions to brainstem monoamine neurochemistry, with increased homovanillic acid:dopamine ratio indicative of increased dopamine turnover, which correlated with the abundance of several bacteria of six different phyla. Interpretation: Chronic antibiotic administration and faecal microbiota transfer disrupt gut microbiota, brainstem monoamine concentrations and the ventilatory response to hypercapnia. We suggest that aberrant microbiota-gut-brain axis signalling has a modulatory influence on respiratory behaviour during hypercapnic stress. Fund: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland. Keywords: Antibiotics, Faecal microbiota transfer, Breathing, Hypercapnia, Cardiovascular, Vagus, Neurochemistry, Intestinal permeability, Microbiota

High-fat diet (HFD) causes renal lipotoxicity that is ameliorated with AMP-activated protein kinase (AMPK) activation. Although bioactive eicosanoids increase with HFD and are essential in regulation of renal disease, their role in the inflammatory response to HFD-induced kidney disease and their modulation by AMPK activation remain unexplored. In a mouse model, we explored the effects of HFD on eicosanoid synthesis and the role of AMPK activation in ameliorating these changes. We used targeted lipidomic profiling with quantitative MS to determine PUFA and eicosanoid content in kidneys, urine, and renal arterial and venous circulation. HFD increased phospholipase expression as well as the total and free pro-inflammatory arachidonic acid (AA) and anti-inflammatory DHA in kidneys. Consistent with the parent PUFA levels, the AA- and DHA-derived lipoxygenase (LOX), cytochrome P450, and nonenzymatic degradation (NE) metabolites increased in kidneys with HFD, while EPA-derived LOX and NE metabolites decreased. Conversely, treatment with 5-aminoimidazole-4-carboxamide-1-β-D-furanosyl 5′-monophosphate (AICAR), an AMPK activator, reduced the free AA and DHA content and the DHA-derived metabolites in kidney. Interestingly, kidney and circulating AA, AA metabolites, EPA-derived LOX, and NE metabolites are increased with HFD; whereas, DHA metabolites are increased in kidney in contrast to their decreased circulating levels with HFD. Together, these changes showcase HFD-induced pro- and anti-inflammatory eicosanoid dysregulation and highlight the role of AMPK in correcting HFD-induced dysregulated eicosanoid pathways.

Pharmacological interventions which could be hepatoprotective, depending on bioavailability, anti-inflammatory and macrophage-targeting potential of drugs, are still at early preclinical stages. Existing evidence from many animal models of liver injury, as well as from human data, indicate that pharmacological and/or phytochemical interventions have limited impact on liver recovery. Recent studies on stem cell therapies focused on different cell subsets involved in tissue repair, including monocytes/macrophages and bone marrow cells migrating to the injured liver. Partial hepatectomy (PH) resulted in a rapid increase of monocytes/macrophages in bone marrow and liver, which could be further enhanced by prior treatment of animals with sodium phthalhydrazide. Increased number of proliferating Ki67+ hepatocytes, increased total protein and albumin content in regenerating liver, recruitment of CD172a+ macrophages and more differentiated CD45lowCD117+ bone marrow cells, could be further promoted by the treatment of animals with 2 mg/kg b.w. phthalhydrazide, considered immunomodulatory, antioxidant and macrophage-silencing. Phenotypic polarization of macrophages can possibly explain the macrophage reparative capacities, protective against liver injury. Enhanced macrophage cell recruitment from bone marrow to regenerating liver can be possibly one of important events in hepatic recovery.

Susceptibility to cigarette smoking, defined as the lack of a firm commitment not to smoke in the future, begins in childhood and is a phase in the transition from never to ever use of cigarettes. While a consistent and validated predictor of cigarette use, little research has assessed whether the susceptibility construct applies equally well across other tobacco products. Baseline data were collected in 2014–2015 from a representative sample of (n = 2844) middle and high school students in five counties surrounding the four largest cities in Texas, (49% female and mean age 13.13 years, with subsequent waves at 6, 12, and 18 months. Confirmatory factor analysis examined the appropriateness of a three-item susceptibility measure (product-specific curiosity, intention to use, and peer influence) across product types and ethnic groups (Hispanic versus non-Hispanic). Logistic regression examined whether product specific susceptibility at baseline predicted future product initiation. At baseline, 11.5%, 17.0%, 17.4% and 29.4%, of adolescent never users were susceptible to cigars, cigarettes, hookah and e-cigarettes, respectively; significantly more Hispanic than non-Hispanic adolescents were susceptible to e-cigarettes (32.4% versus 26%, p

Background: Carotid body (peripheral oxygen sensor) sensitisation is pivotal in the development of chronic intermittent hypoxia (CIH)-induced hypertension. We sought to determine if exposure to CIH, modelling human sleep apnoea, adversely affects cardiorespiratory control in guinea-pigs, a species with hypoxia-insensitive carotid bodies. We reasoned that CIH-induced disruption of gut microbiota would evoke cardiorespiratory morbidity. Methods: Adult male guinea-pigs were exposed to CIH (6.5% O2 at nadir, 6 cycles.hour−1) for 8 h.day−1 for 12 consecutive days. Findings: CIH-exposed animals established reduced faecal microbiota species richness, with increased relative abundance of Bacteroidetes and reduced relative abundance of Firmicutes bacteria. Urinary corticosterone and noradrenaline levels were unchanged in CIH-exposed animals, but brainstem noradrenaline concentrations were lower compared with sham. Baseline ventilation was equivalent in CIH-exposed and sham animals; however, respiratory timing variability, sigh frequency and ventilation during hypoxic breathing were all lower in CIH-exposed animals. Baseline arterial blood pressure was unaffected by exposure to CIH, but β-adrenoceptor-dependent tachycardia and blunted bradycardia during phenylephrine-induced pressor responses was evident compared with sham controls. Interpretation: Increased carotid body chemo-afferent signalling appears obligatory for the development of CIH-induced hypertension and elevated chemoreflex control of breathing commonly reported in mammals, with hypoxia-sensitive carotid bodies. However, we reveal that exposure to modest CIH alters gut microbiota richness and composition, brainstem neurochemistry, and autonomic control of heart rate, independent of carotid body sensitisation, suggesting modulation of breathing and autonomic homeostasis via the microbiota-gut-brainstem axis. The findings have relevance to human sleep-disordered breathing. Funding: The Department of Physiology, and APC Microbiome Ireland, UCC. Keywords: Chronic intermittent hypoxia, Hypertension, Cardiorespiratory control, Microbiome, Guinea-pig

Background: The role of the gut microbiome in the biotransformation of drugs has recently come under scrutiny. It remains unclear whether the gut microbiome directly influences the extent of drug absorbed after oral administration and thus potentially alters clinical pharmacokinetics. Methods: In this study, we evaluated whether changes in the gut microbiota of male Sprague Dawley rats, as a result of either antibiotic or probiotic administration, influenced the oral bioavailability of two commonly prescribed antipsychotics, olanzapine and risperidone. Findings: The bioavailability of olanzapine, was significantly increased (1.8-fold) in rats that had undergone antibiotic-induced depletion of gut microbiota, whereas the bioavailability of risperidone was unchanged. There was no direct effect of microbiota depletion on the expression of major CYP450 enzymes involved in the metabolism of either drug. However, the expression of UGT1A3 in the duodenum was significantly downregulated. The reduction in faecal enzymatic activity, observed during and after antibiotic administration, did not alter the ex vivo metabolism of olanzapine or risperidone. The relative abundance of Alistipes significantly correlated with the AUC of olanzapine but not risperidone. Interpretation: Alistipes may play a role in the observed alterations in olanzapine pharmacokinetics. The gut microbiome might be an important variable determining the systemic bioavailability of orally administered olanzapine. Additional research exploring the potential implication of the gut microbiota on the clinical pharmacokinetics of olanzapine in humans is warranted. Funding: This research is supported by APC Microbiome Ireland, a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (grant no. 12/RC/2273 P2) and by Nature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891).

Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. Funding: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.

Over the last two decades, the scientific community and industry have made huge efforts to develop environmental protection technologies. In particular, the scarcity of drinking water has prompted the investigation of several physico-chemical treatments, and synergistic effects have been observed in hyphenated techniques. Herein, we report the first example of water treatment under simultaneous hydrodynamic cavitation and plasma discharge with the intense generation of radicals, UV light, shock waves and charged particles. This highly reactive environment is well suited to the bulk treatment of polluted water (i.e. E. coli disinfection and organic pollutant degradation). We have developed a new prototype and have efficiently applied this hybrid technology to water disinfection and the complete degradation of methanol in water with the aim of demonstrating its scalability. We have analyzed the mechanisms of water disinfection under the abovementioned conditions and verified them by measuring cavitation noise spectra and plasma emission spectra. We have also used the degradation of textile dyes and methanol solutions as an indicator for the formation of radicals.

Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional lipid risk factors, including low HDL levels, cannot completely explain the increased risk. Altered HDL proteome is linked with both CVD and CKD, but the role of HDL proteins in incident CVD events in patients with CKD is unknown. In this prospective case-control study, we used targeted proteomics to quantify 31 HDL proteins in 92 subjects (46 incident new CVD and 46 one-to-one matched controls) at various stages of CKD. We tested associations of HDL proteins with incident CVD using matched logistic regression analysis. In the model fully adjusted for clinical confounders, lipid levels, C-reactive protein, and proteinuria, no significant associations were found for HDL-C, but we observed inverse associations between levels of HDL proteins paraoxonase/arylesterase 1 (PON1), paraoxonase/arylesterase 3 (PON3), and LCAT and incident CVD. Odds ratios (per 1 SD) were 0.38 (0.18–0.97, P = 0.042), 0.42 (0.20–0.92, P = 0.031), and 0.30 (0.11–0.83, P = 0.020) for PON1, PON3, and LCAT, respectively. Apolipoprotein A-IV remained associated with incident CVD in CKD patients in models adjusted for clinical confounders and lipid levels but lost significance with the addition of C-reactive protein and proteinuria to the model. In conclusion, levels of four HDL proteins, PON1, PON3, LCAT, and apolipoprotein A-IV, were found to be inversely associated with incident CVD events in CKD patients. Our observations indicate that HDLs' protein cargo, but not HDL-C levels, can serve as a marker—and perhaps mediator—for elevated CVD risk in CKD patients.

Changes in axonal myelination are an important hallmark of aging and a number of neurological diseases. Demyelinated axons are impaired in their function and degenerate over time. Oligodendrocytes, the cells responsible for myelination of axons, are sensitive to mechanical properties of their environment. Growing evidence indicates that mechanical properties of demyelinating lesions are different from the healthy state and thus have the potential to affect myelinating potential of oligodendrocytes. We performed a high-resolution spatial mapping of the mechanical heterogeneity of demyelinating lesions using atomic force microscope-enabled indentation. Our results indicate that the stiffness of specific regions of mouse brain tissue is influenced by age and degree of myelination. Here we specifically demonstrate that acquired acute but not genetic demyelination leads to decreased tissue stiffness, which could influence the remyelination potential of oligodendrocytes. We also demonstrate that specific brain regions have unique ranges of stiffness in white and grey matter. Our ex vivo findings may help the design of future in vitro models to mimic the mechanical environment of the brain in healthy and diseased states. The mechanical properties of demyelinating lesions reported here may facilitate novel approaches in treating demyelinating diseases such as multiple sclerosis. Statement of Significance: Mechanical characteristics of a cell's environment can have a profound influence on its biological properties. Neuronal and glial cells are sensitive to mechanical input during development, in disease and regeneration. Sustained tensile strain can promote differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes, which are responsible for the myelination of axons. Changing myelination is an important hallmark in human aging and disease, such as multiple sclerosis. Our hypothesis is that these diseases might be characterized by altered tissue stiffness and that this has an influence on remyelination potential. Here we investigate tissue stiffness profiles of healthy, aged and disease model mice. Manipulating the tissue stiffness might be another promising approach for new treatments.

Summary: Estrogens play an important role in the development and progression of human cancers, particularly in breast cancer. Breast cancer progression depends on the malignant destabilization of adherens junctions (AJs) and disruption of tissue integrity. We found that estrogen receptor alpha (ERα) inhibition led to a striking spatial reorganization of AJs and microclustering of E-Cadherin (E-Cad) in the cell membrane of breast cancer cells. This resulted in increased stability of AJs and cell stiffness and a reduction of cell motility. These effects were actomyosin-dependent and reversible by estrogens. Detailed investigations showed that the ERα target gene and epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) essentially regulates AJ reorganization and E-Cad microclustering. Our results not only describe a biological mechanism for the organization of AJs and the modulation of mechanical properties of cells but also provide a new perspective on how estrogens and anti-estrogens might influence the formation of breast tumors.

Being a valuable agricultural plant, flax (Linum usitatissimum L.) is used for oil and fiber production. However, the cultivation of this agriculture faces an urgent problem of flax susceptibility to fungal diseases. The most destructive ones are caused by the representatives of Fusarium, Colletotrichum, Aureobasidium, Septoria, and Melampsora genera, reducing flax yields significantly. To combat such pathogens effectively, it is of high importance to assess their genetic diversity that can be used to develop molecular markers to distinguish fungal genera and species. Morphological analysis traditionally carried out for fungal identification requires a given amount of time and tends to be difficult. In the present work, we determined the DNA sequences that are frequently used for phylogenetic studies in fungi – internal transcribed spacer (ITS) and beta-tubulin (tub2), translation elongation factor 1-alpha (tef1), RNA polymerase II largest subunit (RPB1), RNA polymerase II second largest subunit (RPB2), and minichromosome maintenance protein (MCM7) genes – for 203 flax fungal pathogens of Fusarium oxysporum, F. avenaceum, F. solani, F. sporotrichiella, F. moniliforme, F. culmorum, F. semitectum, F. gibbosum, Colletotrichum lini, Aureobasidium pullulans, Septoria linicola, and Melampsora lini species. The sequencing was performed using the Illumina MiSeq platform with a 300+300 bp kit, and on average, about 2350 reads per sample were obtained that allows accurate identification of the genetic polymorphism. Raw data are stored at the Sequence Read Archive under the accession number PRJNA596387. The obtained data can be used for fungal phylogenetic studies and the development of a PCR-based test system for flax pathogen identification.

Insulin gene (INS) mutations prove to be the second most common cause of permanent neonatal diabetes. Here, we report the generation of iPSC line from a patient, heterozygous for the intronic INS mutation that presumably leads to aberrant splicing. Dermal fibroblasts were reprogrammed using non-integrating RNA-based vector. Derivation and expansion of iPSCs were performed under feeder-free culture conditions. The iPSC line expressed pluripotency markers, had normal karyotype, could differentiate into three germ layers in vitro and retained the disease mutation. This line can be a powerful tool for modeling of diabetes and cell replacement therapy as well.

Background: Since 2012, the BC Cancer provincial treatment guideline for surgically staged stage IA/B and IC1 (defined by intraoperative rupture only) clear cell ovarian cancer (CCOC) has been to offer observation only. We reviewed the clinical outcomes of all stage I CCOC patients since policy implementation. Methods: A retrospective, population-based cohort study of all stage I CCOC patients operated on between April 2012 and December 2017 was conducted. Patient, tumor, surgical and clinical outcome data were collected. Survival analysis was conducted using Kaplan-Meier methods. Results: 78 patients with stage I disease were identified. 40 patients with stages IA/B and IC1, who underwent post-operative observation, were included in the analysis. Lymph node dissection was omitted in 20 patients (50%). Median duration of follow-up was 36 months. There were 4 recurrences (10%), 3 metastatic. The 5-year disease-free survival is 90%, and the 5-year overall survival is 95% for stage IA/B and 90% for stage IC1 (p = 0.645). In comparison, 5-year overall survival for stage IC2 (surface involvement) and IC1 with sharp dissection (all received adjuvant chemotherapy) is 82% (p 90% at 5 years. Stage IC2 /IC3 had worse outcomes, thus stage I substage is instrumental in predicting clinical outcomes for CCOC. Lymph node metastases are rare in stage IA/B/C1 CCOC as absence of lymphadenectomy did not increase the risk of disease recurrence. Keywords: Clear cell carcinoma, Ovarian cancer, Adjuvant therapy

Background and purpose: Chromosomal aberrations in peripheral blood lymphocytes are a biomarker for radiation exposure and are associated with an increased risk for malignancies. To determine the long-term cytogenetic effect of radiotherapy, we analyzed the persistence of different aberration types up to 2.5 years after the treatment. Materials and methods: Cytogenetic damage was analyzed in lymphocytes from 14 patients that had undergone C-ion boost + IMRT treatment for prostate cancer. Samples were taken immediately, 1 year and 2.5 years after therapy. Aberrations were scored using the multiplex fluorescence in situ hybridization technique and grouped according to their transmissibility to daughter cells. Results: Dicentric chromosomes (non-transmissible) and translocations (transmissible) were induced with equal frequencies. In the follow-up period, the translocation yield remained unchanged while the yield of dicentrics decreased to ≈40% of the initial value (p = 0.011 and p = 0.001 for 1 and 2.5 years after compared to end of therapy). In 2 patients clonal aberrations were observed; however they were also found in samples taken before therapy and thus were not radiotherapy induced. Conclusion: The shift in the aberrations spectrum towards a higher fraction of translocations indicates the exposure of hematopoietic stem and progenitor cells underlining the importance of a careful sparing of bone marrow during radiotherapy to minimize the risk for secondary cancers. Keywords: Prostate cancer, Carbon ion therapy, Hematopoietic stem cells, Bone marrow, Chromosomal translocations, Risk assessment