Perinatal mortality is a major issue in laboratory mouse breeding. We compared a counting method using daily checks (DAILY_CHECK) with a method combining daily checks with detailed video analyses to detect cannibalisms (VIDEO_TRACK) for estimating the number of C57BL/6 pups born, died and weaned in 193 litters from trios with (TRIO-OVERLAP) or without (TRIO-NO_OVERLAP) the presence of another litter. Linear mixed models were used at litter level. To understand if cannibalism was associated with active killing (infanticide), we analysed VIDEO_TRACK recordings of 109 litters from TRIO-OVERLAP, TRIO-NO_OVERLAP or SOLO (single dams). We used Kaplan-Meier method and logistic regression at pup level. For DAILY_CHECK, the mean litter size was 35% smaller than for VIDEO_TRACK (P<0.0001) and the number of dead pups was twice lower (P<0.0001). The risk of pup loss was higher for TRIO-OVERLAP than TRIO-NO_OVERLAP (P<0.0001). A high number of pup losses occurred between birth and the first cage checking. Analyses of VIDEO_TRACK data indicated that pups were clearly dead at the start of most of the cannibalism events and infanticide was rare. As most pups die and disappear before the first cage check, many breeding facilities are likely to be unaware of their real rates of mouse pup mortality.

Cas endonuclease-mediated genome editing provides a long-awaited molecular biological approach to the modification of predefined genomic target sequences in living organisms. Although cas9/guide (g)RNA constructs are straightforward to assemble and can be customized to target virtually any site in the plant genome, the implementation of this technology can be cumbersome, especially in species like Triticale that are difficult to transform, for which only limited genome information is available and/or which carry comparatively large genomes. To cope with these challenges, we have pre-validated cas9/gRNA constructs (1) by frameshift restitution of a reporter gene co-introduced by ballistic DNA transfer to barley epidermis cells, and (2) via transfection in Triticale protoplasts followed by either a T7E1-based cleavage assay or by deep-sequencing of target-specific PCR amplicons. For exemplification, we addressed the Triticale ABA 8’-hydroxylase 1 gene, one of the putative determinants of pre-harvest sprouting of grains. We further show that in-del induction frequency in Triticale can be increased by TREX2 nuclease activity, which holds true for both well- and poorly performing gRNAs. The presented results constitute a sound basis for the targeted induction of heritable modifications in Triticale genes.

There is still an ambiguous opinion on oat regarding its safety for people with celiac disease (CD). Some studies have confirmed different content of oat immunoreactive epitopes in different cultivars while others explain the differences in consequence of cross-contamination with gluten-rich species or as ELISA cross-reactivity of oat homological epitopes with antibodies against wheat gliadin. Our study was based on a two-year mapping of oat immunoreactive epitopes in a set of 132 oat cultivars using the G12-based ELISA kit. Although repeated evaluation confirmed high interannual variability (RSD ≥ 30%) in approximately 2/3 of the cultivars, the permitted gluten content (20 mg kg-1) has not been exceeded except for contaminated cultivar Sirene. The polymorphism of purified avenins determined by SDS-PAGE revealed the occurrence of 2 bands around 30 kDa in oat cultivars with relatively high gluten content (12-16 mg kg-1) except for the cultivar Leo while this pattern occurred only in 50% oat cultivars with low gluten content. Quantification of gluten epitopes on purified avenin unit further revealed the three materials (Mojacar, Maris Oberon, SG-K 16370) with the lowest gluten content and presence of one band at 30 kDa. The band pattern at 30 kDa thus represents a promising breeding marker.

In the last two decades, extracellular vesicles (EVs) from the three domains of life, archae, bacteria and eukaryota, have gained increasing scientific attention. As such, the role of EVs in host-pathogen communication and immune modulation are being intensely investigated. Pivotal to EV research is the determination of how and where EVs are taken up by recipient cells and organs in vivo, which requires suitable tracking strategies including labelling. Labelling of EVs is often performed post-isolation which increases risks of non-specific labelling and the introduction of labelling artefacts. Here we exploited the inability of helminths to de novo synthesise fatty acids to enable labelling of EVs by whole organism uptake of fluorescent lipid analogues and the subsequent incorporation in EVs. We showed uptake of DOPE-Rhodamine in Anisakis spp. and Trichuris suis larvae. EVs isolated from supernatant of Anisakis spp. labelled with DOPE-Rhodamine were characterised to assess effects of labelling on size, structure and fluorescence of EVs. Fluorescent EVs were successfully taken up by the human macrophage cell line THP-1. This study therefore presents a novel staining method that can be utilized by the EV field in parasitology and potentially across multiple species.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

The paper presents construction, laboratory tests as well as the first field application of a new fiber-optic rotational seismograph. The system based on fiber-optic gyroscope (FOG) with determined Angle Random Walk of the order of 10-8 rad/Sqrt(s) and a few rad/s maximum detectable amplitude of rotation in the frequency range from DC to 328.12 Hz. It has been designed for rotational seismology area of interest. This work also presents exemplary relevant measurements which were conducted using a set of two devices installed in the geophysical observatory in Książ, Poland.

Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). The co-occurrence of ARMs and CSS in an individual is unexpected since both diseases are very rare. A review of the literature enabled us to identify 12 individuals with both CSS and ARMs. Among these 12 individuals, 9 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are likely a rare consequence of CSS, especially for ARID1A-related CSS.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

The increading emission of carbon dioxide to the atmosphere has urged the scientific community to investigate alternatives to alleviate such emissions being the principal contributor to the greenhouse gas effect. One major alternative is carbon capture and utilisation (CCU) towards the production of value-added chemicals using diverse technologies. This work aims at the study of the catalytic potential of different cobalt-derived nanoparticels for methanol syntheis from carbon dioxide hydrogenation. Thanks to its abundance and cost-efficacy, cobalt can serve as an economical catalyst compared to noble-metal-based catalysts. In this work, we present a systematic comparison among different cobalt and cobalt oxide nanocomposites in terms of their efficiency as catalysts for carbon dioxide hydrogenation to methanol as well as how different supports can enhance their catalytic capacity. The oxygen vacancies in the cerium oxide act as carbon dioxide adsorption and activation sites, which facilitates a higher methanol production yield.

The 3D/3D+ multidimensional geriatric assessment tool provides an optimal model of emergency care for patients aged 75 and over who attend the Emergency Department (ED). The baseline, or static, component (3D) stratifies the degree of frailty prior to the acute illness, while the current, or dynamic, component (3D+) assesses the multidimensional impact caused by the acute illness and helps to guide the choice of care facility for patients upon their discharge from the ED. The objective of this study was to evaluate the prognostic value of the 3D/3D+ to predict short- and long-term adverse outcomes in ED patients aged 75 years and older. Multivariable logistic regression models were used to identify the predictors of mortality 30 days after 3D/3D+ assessment. Two hundred and seventy-eight patients (59.7% women) with a median age of 86 years (interquartile range: 83-90) were analysed. According to the baseline component (3D), 83.1% (95%CI: 78.2-87.3) presented some degree of frailty. The current component (3D+) presented alterations in 60.1% (95%CI: 54.1-65.9). The choice of care facility at ED discharge indicated by the 3D/3D+ was considered appropriate in 96.4% (95%CI: 93.0-98.0). Thirty-day all-cause mortality was 19.4%. Delirium and functional decline were the dimensions on the 3D/3D+ that were independently associated with 30-day mortality. These two dimensions had an area under receiver operating characteristic of 0.80 (95%CI: 0.73-0.86) for predicting 30-day mortality. 3D/3D+ enhances the provision of comprehensive care by ED professionals, guides them in the choice of patients’ discharge destination, and has a prognostic validity that serves to establish future therapeutic objectives.

Water deficit greatly affects global crop growth and productivity, particularly in water-limited environments like upland rice cultivation, leading to reduced grain yield. Plants activate various defense mechanisms during water deficit, involving numerous genes and complex metabolic pathways. Exploring orthologous genes, linked to enhanced drought tolerance, can aid functional validation in target species using genomic data from model organisms. Here, we studied the OsCPK5 gene in upland rice, an AtCPK6 ortholog from A. thaliana, by overexpressing it in the BRSMG Curinga cultivar. Transformants were assessed under two conditions: water deficit applied 79 days after seeding, lasting 14 days, followed by 7 days of irrigation at 80% field capacity. Physiological data and samples were collected at R3, R6, and R8 stages. GM plants consistently exhibited higher OsCPK5 gene expression across stages, peaking during grain filling. During this phase, GM plants displayed reduced stomatal conductance, photosynthetic rate, and increased water use efficiency compared to non-GM plants under drought. GM plants also exhibited higher filled grain percentage in both irrigation conditions. Their drought susceptibility index was 0.9 times lower than NGM plants, and they maintained a higher chlorophyll a/b index, indicating sustained photosynthesis. NGM plants under water deficit exhibited more leaf senescence, while OsCPK5-overexpressing plants retained green leaves. Overall, OsCPK5 overexpression induced diverse drought tolerance mechanisms, hinting at potential for future development of more drought-tolerant rice cultivars.

Age-related macular degeneration is one of the most common causes of blindness, and the incidence exhibits profound racial bias, occurring most frequently in Caucasians. A primary cell type affected in the disease is the retinal pigment epithelium, but the etiology is unclear. The end 10% of the photoreceptor outer segments are shed each day, and the underlying retinal pigment epithelium engulfs, digests, and recycles molecules back to the sensory retina. In previous work, we showed that GPR143 signaling in response to L-DOPA may be effective in the prevention or delay of age-related macular degeneration. In this study, we explore a novel potential effector of GPR143 signaling, that of outer segment uptake and digestion. Using isolated outer segments, labelled with a pH-sensitive marker to fluoresce in lysosomes, we show that GPR143 signaling does not impact outer segment uptake, but does have a significant effect on subsequent degradation. Interestingly, GPR143 signaling did not affect the digestive capacity of the cells, marked by total proteolytic capacity and cathepsin D activity. Rather, our data suggest GPR143 improved endosomal trafficking efficiency of the phagocytosed outer segments to the lysosome. This result is similar to the effect we previously reported for GPR143 on exosome release from the endosomal compartment. Our data illustrate that GPR143 is active in endosomal traffic A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Online reinforcement learning (RL) algorithms are increasingly used to personalize digital interventions in the fields of mobile health and online education. Common challenges in designing and testing an RL algorithm in these settings include ensuring the RL algorithm can learn and run stably under real-time constraints, and accounting for the complexity of the environment, e.g., a lack of accurate mechanistic models for the user dynamics. To guide how one can tackle these challenges, we extend the PCS (Predictability, Computability, Stability) framework, a data science framework that incorporates best practices from machine learning and statistics in supervised learning (Yu and Kumbier, 2020), to the design of RL algorithms for the digital interventions setting. Further, we provide guidelines on how to design simulation environments, a crucial tool for evaluating RL candidate algorithms using the PCS framework. We illustrate the use of the PCS framework for designing an RL algorithm for Oralytics, a mobile health study aiming to improve users' tooth-brushing behaviors through the personalized delivery of intervention messages. Oralytics will go into the field in late 2022.

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilizing the membrane protein arrangement in the virion. The residues responsible for the M protein inter-actions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein, which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.

We have used Mass Multivariate Method on structural, resting state and task related fMRI data from two groups of patients with schizophrenia and depression, respectively, in order to define several regions of significant relevance to the differential diagnosis between those conditions. The regions included the left Planum polare, Left opercular part of the inferior frontal gyrus (OpIFG), Medial orbital gyrus (MOrG), Posterior Insula (PIns), and Parahippocampal gyrus (PHG). This study delivers evidence that multimodal neuroimaging approach can potentially enhance the validity of psychiatric diagnosis. Either structural, or resting state or task related functional MRI modality cannot provide independent biomarkers. Further studies need to consider and implement a model of incremental validity to combine clinical measures with different neuroimaging modalities to discriminate depressive disorders from schizophrenia. Biological signatures of disease on the level of neuroimaging are more likely to underpin broader nosological entities in psychiatry.

Forty-eight Pasteurella multocida isolates were recovered from porcine pneumonic lungs collected in Norwestern Spain (2017- 2019). These isolates were characterized for their minimal inhibition concentrations to twelve antimicrobial agents and for the appearance of eight resistance genes: tetA, tetB, blaROB1, blaTEM, ermA, ermC, mphE and msrE. Relevant resistance percentages were shown to teracyclines, sulphamethoxazole/trimethoprim and tiamulin, thus suggesting that P. multocida isolates were mostly susceptible to amoxicillin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin and macrolides. 29.2% of isolates were resistant to more than two antimicrobials. The tetracycline resistance genes (tetA and tetB) were detected in 22.9% of the isolates, but none was positive to both simultaneously; blaROB1 and blaTEM genes were found in one third of isolates but both genes were detected simultaneously in only one isolate. ermC gene was observed in 41.7% of isolates, a percentage that decreased until 22.9% for msrE; finally, ermA was harboured by 16.7% and mphE was not found in any of them. Six clusters were established based on hierarchical clustering analysis on antimicrobial susceptibility for the twelve antimicrobials. Generally, it was unable to foresee the antimicrobial susceptibility pattern for each family and the association of each particular isolate inside the clusters established from the presence or absence of the resistance genes analyzed.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

Background: The present study compared corticospinal excitability to the biceps brachii muscle during arm cycling at a self-selected and a fixed cadence (SSC and FC, respectively). We hypothesized that corticospinal excitability would not be different between the two conditions. Methods: The SSC was initially performed and the cycling cadence was recorded every 5 seconds for one minute. The average cadence of the SSC cycling trial was then used as a target for FC of cycling that the participants were instructed to maintain. Motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the biceps brachii during each trial of SSC and FC arm cycling. Results: Corticospinal excitability as assessed via normalized MEP amplitudes (MEPs were made relative to a maximal compound muscle action potential) were not different between groups. Conclusions: Focusing on maintaining a FC cadence during arm cycling does not influence corticospinal excitability as assessed via TMS-evoked MEPs.

A variety of environmental factors contribute significantly to age-related cognitive decline and Alzheimer’s Disease (AD). Nutrition can alter epigenetics, improving health outcomes, which transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in offspring. We feed females SAMP8 with resveratrol-enriched diet during two months prior to mating. Direct exposed F1 generation and the transgenerational F2 generation were investigated. Object novel recognition and Morris water maze demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring resulted from resveratrol fed mother showed increase AMPKα activation, mTOR inhibition and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.

Talking about sustainable development refers mainly to the environmental sphere, but the concept is much broader and also takes into account the social and economic conditions. The concept of sustainability, in this sense, is linked to the compatibility between the development of economic activities, the related social phenomena, and the protection of the environment. Therefore, the ability to balance social, economic and environmental sustainability is the very meaning of the concept of sustainable development. Firms that choose to develop policies and strategies to enhance and pursue sustainable development in the medium to long term have the burden of having to quantitatively document the improvements in production processes with the aim of sustainable development. As a result, one of the biggest challenges for European industry is to introduce sustainability principles into business models leading to competitive advantage. This is particularly important in raw material and energy intensive manufacturing sectors such as the ceramic industry. The present state of knowledge lacks a comprehensive operational tool for industry to support decision-making processes geared towards sustainability. In the ceramic sector, the economic and social dimensions of the product and processes have not yet been given sufficient importance. Moreover, the traditional research on industrial districts lacks an analysis of the relations between firms and the territory with a view to sustainability. Finally, the attention of scholars in the field of economic and social sustainability, has not yet turned to the analysis of the Sassuolo district. Therefore, in this paper we introduce the Life Cycle Sustainability Assessment (LCSA), as a method that can be a suitable tool to fill this gap, because through a mathematical model it is possible to obtain the information useful for decision makers to integrate the principles of sustainability both at the microeconomic level in enterprises, and at the meso-economic level for the definition of economic policies and territorial governance. Environmental and socio-economic analysis was performed from the extraction of raw materials to the packaging of the product on different product categories manufactured by the Italian ceramic industries of the Sassuolo district (northern Italy). For the first time the LCSA model, usually applied to unitary processes, is extended to the economic and industrial activities of the entire district, extending the prospect of investigation from the enterprise and its value chain to the integrated network of district enterprises.

Solving environmental odor issues can be confounded by many analytical, technological, and socioeconomic factors. Considerable know-how and technologies can fail to properly identify odorants responsible for the downwind nuisance odor and mitigate it for the affected citizenry. We propose enabling solutions to environmental odor issues by utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries. We showed that the downwind odorant impact-priority ranking process can be definable and relatively simple. The initial challenge is the prioritization of environmental odor character from the perspective of the impacted citizenry downwind. In this research, we aim at summarizing three natural models of the rolling unmasking effect (RUE) and discuss them more systematically in the context of the proposed downwind environmental odor prioritization approach. Regardless of the size and reach of an odor source, a simplification of odor character and composition typically develops with downwind dilution. The extreme odor simplification-upon-dilution was demonstrated for two plant varieties, prairie verbena and Virginia pepperweed. Their downwind odor frontal boundaries were dominated by single, character-defining odorants; p-cresol-dominated ‘barnyard’ odor, and benzyl mercaptan-dominated ‘burnt match’ odor, respectively. The P.T. porcupine downwind odor frontal boundary was dominated by two potent, character-defining odorants: (1) ‘onion’/‘body odor’ odorant #1 and (2) ‘onion’/‘grilled’ odorant #2. In contrast with their downwind boundary simplicities, each odor source presented considerable compositional complexity and composite character difference near the source. The proposed RUE approach’s ultimate significance is the illustration of naturally occurring phenomena that explain why some environmental odors and their sources can be challenging to identify and mitigate using the analytical only approach (focused on compound identities and concentrations). These approaches rarely move beyond comprehensive lists of compounds being emitted by the source.

The hybrid zone between chromosome races of the common shrew (Sorex araneus) provides an exceptional model to study the potential role of chromosome rearrangements in the initial steps of speciation. The Novosibirsk and Tomsk races differ by a series of Robertsonian fusions with monobrachial homology. They form a narrow hybrid zone and generate hybrids with both simple (chain of three chromosomes) and complex (chain of eight or nine) synaptic configurations. Using immunolocalisation of the meiotic proteins, we examined chromosome pairing and recombination in males from the hybrid zone. Homozygotes and simple heterozygotes for Robertsonian fusions showed a low frequency of synaptic aberrations (< 10%). The carriers of complex synaptic configurations showed multiple pairing abnormalities, which might lead to reduced fertility. Recombination frequency in the proximal regions of most chromosomes of all karyotypes was much lower than in the other regions. The strong suppression of recombination in the pericentromeric regions and co-segregation of race specific chromosomes involved in the long chains would be expected to lead to linkage disequilibrium between genes located there. Genic differentiation, together with the high frequency of pairing aberrations in male carriers of the long chains, might contribute to maintenance of the narrow hybrid zone.

Background: Endoplasmic reticulum (ER) stress is a significant player in the pathophysiology of various neurodegenerative and neuropsychiatric disorders. Despite the established link between ER stress and inflammatory pathways, there remains a need for deeper exploration of the specific cellular mechanisms underlying ER stress-mediated neuroinflammation. Methods: This study aimed to investigate how severity of ER stress can impact the release of proinflammatory cyto-kines IL-6 and IL-8 from astrocytes and microglia, comparing the effects with those induced by well-known immunostimulants - tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS). Results: Mild ER stress has a distinct effect on the cytokine release compared to more intense stress levels, i.e. diminished IL-6 production was accompanied by an increase in IL-8 level, which was significantly more pronounced in astrocytes than in microglia. On the contrary, prolonged or more severe ER stress induced inflammation in glial cells, leading to a time- and concentration-dependent buildup of pro-inflammatory IL-6 but unlike inflammatory agents, ER stress inducer diminished IL-8 secretions by glial cells. Conclusion: The differences could hold importance in identifying ER stress markers as potential drug targets for treatment of neurodegenerative diseases or mood disorders, yet it requires confirmation in more complex animal studies.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

The paper provides and comments on the results of studies of the effect of sandstone-based abrasives and quartz sand alone on the wear of martensitic surfaces of wear-resistant steels. The wear process was examined on a ring-on-ring test rig seeking to determine the mass decrement parameter which characterised wear. The tests were conducted for three sandstone varieties: Carboniferous, Permian, and Cretaceous, and they made it possible to determine that the most intense process of deterioration of wear-resistant steels took place in the presence of quartz sand grain, while less intense wear was observed in the case of sandstone-based abrasives. The mass decrement values established in the presence of the sandstones in question did not differ significantly between individual sandstone varieties. Based on a surface damage analysis, the basic damage mechanism was found to be micro-scratching, however, with regard to the sandstones examined, it was also determined that individual grains could be pressed into surface irregularities, as well as that films of soft hematite cement developed in the Permian sandstone and that inclusions of carbonaceous matter were formed in the Carboniferous sandstone. With reference to the wear process observations, a wear model was described for the surface of the steels examined in the presence of sandstone-based abrasives.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women in the childbearing age. Pregnancy in SLE patients poses unique challenges due to the po-tential impact on maternal and fetal outcomes. We provide an overview of the management of SLE during pregnancy, including pre-conception risk stratification and counselling, treatment, and disease activity monitoring. These assessments are critical to minimize maternal and fetal adverse events in SLE pregnant patients. Disease flares, preeclampsia, antiphospholipid syn-drome complications, and maternal mortality are the major risks for a woman with SLE during gestation. Timely treatment of SLE relapse, differentiation of preeclampsia from lupus nephritis, and tailored management for antiphospholipid syndrome are essential for a successful pregnan-cy. Fetal outcomes include neonatal lupus (NL), preterm birth, cesarean delivery, fetal growth re-striction (FGR), and small for gestational age (SGA) infants. We focused on NL, linked to mater-nal anti-Ro/SS-A and anti-La/SS-B antibodies, which can lead to various manifestations, partic-ularly cardiac abnormalities in newborns. While there is a common consensus regarding the pre-ventive effect of hydroxychloroquine, the role of echocardiographic monitoring and fluorinated steroid treatment is still debated. Finally, close postpartum monitoring and counseling for sub-sequent pregnancies are crucial aspects of care.

The human voice has the potential to serve as a valuable biomarker for the early detection, diagnosis, and monitoring of pediatric conditions. This scoping review synthesizes the current knowledge on the application of Artificial Intelligence (AI) in analyzing pediatric voice as a biomarker for health. The included studies featured voice recordings from pediatric populations aged 0-17 years, utilized feature extraction methods, and analyzed pathological biomarkers using AI models. Data from 62 studies were extracted, encompassing study and participant characteristics, recording sources, feature extraction methods, and AI models. The review showed a global representation of pediatric voice studies, with a focus on developmental, respiratory, speech, and language conditions. The most frequently studied conditions were Autism Spectrum Disorder, intellectual disabilities, asphyxia, and asthma. Mel-Frequency Cepstral Coefficients were the most utilized feature extraction method, while Support Vector Machines were the predominant AI model. The analysis of pediatric voice using AI demonstrates promise as a non-invasive, cost-effective biomarker for a broad spectrum of pediatric conditions. However, further research and development are crucial to enhance the accuracy and applicability of these tools in clinical settings.

Bats are natural hosts for a wide variety of viruses and could therefore be the reservoir, source and spillover for several mammalian viruses, including adenoviruses. We examined faecal samples from 12 bats (five species of the family Vespertilionidae) from central Russia (Moscow Region) and found that two of them (16%) were positive for mastadenoviruses. One of the identified viruses was isolated from faeces of Nyctalis noctule and named BatAdV/MOW15-Nn19. The genome of the BatAdV/MOW15-Nn19 was 37,915 bp in length. Comparative studies have shown significant divergence of the nucleotide sequence of the BatAdV/MOW15-Nn19 genome from European mastadenoviruses, the highest genome sequence similarity was to isolate WA3301 from an Australian bat. Phylogenetic analysis, as well as a comparative analysis of the protein coding genes to homologous available from public database, showed evidence of novel species within Mastadenovirus genus (preliminary named «K»). Analysis of the short part of the DNA polymerase gene of BatAdV/MOW15-Nn19 reveals few NCBI records from Europe with high identity to the new virus, i.e. mastadenoviruses related to the new species are circulating in European bats. The partial genome of another mastadenovirus from Pipistrellus nathusii was identified, it represented bat adenovirus species B, which is widely distributed in European Vespertilionidae bats. New data on the genetic diversity of bat adenoviruses may help to better understand how they evolved in mammals and spread across Europe.

Τhis study aims to assess changes in the fovea avascular zone (FAZ) in treatment naïve patients receiving aflibercept or ranibizumab injections for diabetic macular edema (DME). This is a prospective study recruiting patients with treatment-naïve DME. Best corrected visual acuity (BCVA) testing, OCT and OCT-angiography (OCTA) imaging were performed at baseline and 1 month after each injection. Injections of either aflibercept or ranibizumab were administered monthly for 6 consecutive months. FAZ in the superficial (SCP) and the deep capillary plexus (DCP) using OCTA was recorded for each visit. Fifty eyes from 50 patients with a mean age of 67.010.7 years were included in the study Twenty-five patients received aflibercept and 25 received ranibizumab. BCVA was 40.810.0 and increased to 52.17.9 ETDRS letters at the last visit (p&lt;0.001). CRT was 295.634.0 at baseline and 247.929.7 at the last study visit (p&lt;0.001). SCP FAZ was 350.679.5μm2 at baseline and 339.071.3μm2 after 6 monthly injections (p=0.132). DCP FAZ was 558.6199.0μm2 at baseline and 459.5156.1μm2 after 6 monthly injections (p&lt;0.001). There was no effect of the choice of ranibizumab or aflibercept on DCP FAZ change (p=0.277). In conclusion, treatment with 6 monthly injections of ranibizumab and aflibercept led to an increase in BCVA and a decrease in CRT and DCP FAZ area. Both drugs led to an improvement in DCP ischemia.

Stroke survivors often face diverse unmet needs, highlighting the significance of identifying and addressing these needs to enhance rehabilitation outcomes and overall quality of life. This study aimed to validate the modified Needs Assessment Questionnaire (mNAQ) as a reliable and valid tool for assessing the needs of stroke patients in the Greek context. Additionally, the research sought to identify potential differences in the assessment of stroke patients' needs based on their stroke phase and National Institutes of Health Stroke Scale (NIHSS) scores. A sample of 71 adult stroke survivors, adhering to World Health Organization guidelines and providing autonomous consent, participated in the study. The mNAQ, comprising 141 items across 12 domains, was uti-lized to evaluate stroke patients' needs. The NIHSS and Barthel Index (BI) were employed for functional independence and mobility assessment. Data analysis incorporated confirmatory fac-tor analysis, exploratory factor analysis, and Cronbach's reliability analysis to establish con-struct validity and internal consistency. Concurrent and known-groups validity analyses were conducted, and Spearman’s rho correlation explored the relationship between mNAQ and BI scores. Non-parametric analyses were applied to identify differences based on stroke phase and NIHSS scores. The study revealed that the mNAQ initially lacked satisfactory psychometric properties in the Greek context. Subsequent modifications, guided by confirmatory and explora-tory factor analyses, resulted in a refined three-factor scale encompassing 31 items in the domains of communication, mobility, and social functioning needs. This adapted measure effectively dif-ferentiated between acute and chronic stroke patients and those with minor and moderate strokes. In conclusion, the validated 31-item Greek mNAQ emerges as a crucial tool for compre-hensively assessing the needs of stroke patients. Its application holds promise for optimizing post-stroke care, improving functional outcomes, and ultimately enhancing the overall well-being and quality of life for stroke survivors.

Bioactive compound profiles in organic and conventional sweet basil were analyzed by HPLC, and the enzymatic status and antioxidant status of plants cultivated with the two systems were also examined. Unique chemical compound locations in the basil leaves were also estimated by fluorescence microscopy. The experiment was conducted from 2019-2021. Organic and conventional basil samples were obtained directly from the largest Polish herb producers. The results showed that the chemical structures of organic and conventional basil leaves are different. Not only cultivation method but also experimental year had a significant impact on the antioxidants content in basil leaves. Organic basil contained significantly more dry matter (11.97 g 100 g-1 FW) compare to conventional one (10.54 g 100g-1 FW) and showed a higher tendency for total phenolic (5.24 mg g -1 DW) concentrations than conventional basil (4.99 mg g-1 DW). The higher bioactive compound content reflects the antioxidant activity ( 61.0%, 54.33% and 46%) in organic basil compare to conventional 46.87%, 38.055 and 39.24%), respectively to analysis method (ABTS, DPPH and FRAP), as well catalase activity (39 µmol H2O2 min-1 mg-1) in organic compare to conventional (23.19 µmol H2O2 min-1 mg-1) of examined basil plants. The obtained results are a very unique and could be used by herbs producers as a key for q high quality basil production.

Poplar (Populus) is a genus of woody plants of value for the pulp industry, green energy, urban landscaping, soil phytoremediation and as an ornamental plant. Due to the increasing economic importance of poplar, there is a need to ensure its stable growth by increasing its resistance to pathogens, as one of the main problems in poplar cultivation is its susceptibility to numerous diseases. Currently, breeding poplars with reduced susceptibility to infections is receiving increasing attention. Genetic engineering can produce organisms with improved traits faster than traditional methods, and with the development of CRISPR/Cas-based genome editing systems, scientists have a new highly efficient tool at their disposal to create valuable genotypes. In this review, we summarize recent research data on poplar diseases, the biology of their pathogens, and how these plants resist pathogens. In the final section, we discuss genetic engineering, genome editing, and microbiome strategies that we believe are suitable for obtaining new improved poplar lines.

Objectives: Non-adhesive gel-like embolic materials (NAGLEMs) are becoming increasingly dominant in the endovascular treatment of hypervascularised formations in the head and neck due to a combination of their key properties. The main advantages include their lack of adhesion, effective distribution and penetration through pathological vessels, and crucially, their controlla-bility during the process. Our assigned duty was to scrutinise the literature and assess the efficacy and outcomes of administering NAGLEMs, in comparison to other embolizing substances (name-ly, coils, glue, and particles), among patients treated at our clinic. The procedures involved ana-lyzing the technical aspects, efficiency, and safety of endovascular therapy applied to two catego-ries of hypervascular pathological anomalies, surgically managed from 2015 to 2023. Arteriove-nous malformations (AVMs) located in the head, neck, and paragangliomas with jugular/carotid body localization are combined by intense shunting blood flow and shared requirements for em-bolizates used in endovascular treatment (such as penetration, distribution, delayed polymeriza-tion and controllability). An analysis of the literature was also conducted. Results showed 18 pa-tients diagnosed with neck paragangliomas of the carotid body and jugular type. Five patients with arteriovenous malformation (AVM) of the face and neck were included, consisting of 16 fe-males and 7 males with an average age of 55 ± 13 years. Endovascular procedures were conduct-ed using NAGLEMs (ONYX (Medtronic), SQUID (Balt), and PHIL (Microvention)) and dimethyl sulfoxide (DMSO)-compatible balloon catheters. All patients achieved complete or partial embo-lization of hypervascularized formations using one or more stages of endovascular treatment. Additionally, three AVMs of the face and two paragangliomas of the neck were surgically ex-cised following embolization. In other instances, formations were not deemed necessary to be re-moved. The patients' condition upon discharge was assessed by the modified Rankin Scale (mRs) and rated between 0 and 2. Conclusion: Currently, NAGLEMs are predominantly used to treat hypervascularized formations in the neck and head due to their fundamental properties. These properties include a lack of adhesion and a delay in predictable polymerization (after 30-40 minutes). NAGLEMs also exhibit excellent distribution and penetration throughout the vascular bed of the formation. Adequate controllability of the process is largely achieved through the pres-ence of embolism forms of different viscosity, as well as excellent X-ray visualization.

Candidatus Accumulibacter belongs to phosphate-accumulating organisms (PAO) which exhibit cyclic metabolism and are capable of intracellular polyphosphate accumulation and their hydrolysis under feast-famine anaerobic-aerobic cycling. In consortia of activated sludge microorganisms, these bacteria are responsible for enhanced biological phosphorus removal (EBPR). The spectrum of the substrates used by Ca. Accumulibacter remains insufficiently studied. It was investigated by measuring the oxygen uptake rates (OUR) of Ca. Accumulibacter-enriched culture supplemented with 17 different organic substrates. The highest oxygen uptake rates values were observed in the presence of tryptone, volatile fatty acids (acetate, propionate, and butyrate), succinate, pyruvate, and amino acids (aspartate and glutamate). Phosphate dynamics in the medium under shifts from anaerobic to aerobic cultivation in batch experiments was studied for these compounds (except for tryptone). All tested substrates were shown to cause phosphate cycling (release in the anaerobic phase and uptake in the aerobic one), with OURs for the substrates correlating with the amount of phosphates consumed during the aerobic phase. It was concluded that OUR may be used as an indicator of the monosubstrates used by Ca. Accumulibacter in the anaerobic/aerobic cycle. The possible pathways for substrate transport and metabolism by Ca. Accumulibacter are discussed using the stoichiometric data and the results of metagenomic analysis.

The growing dependence on large language models (LLM)s highlights the urgent need to deepen trust in these technologies. Regular, rigorous validation of their expertise, especially in nuanced and intricate scenarios, is essential to ensure their readiness for clinical applications. Our study pioneers the exploration of LLM utility in the field of cardiology. We stand at the cusp of a transformative era where mature AI and LLMs, notably ChatGPT, GPT-4, and Google Bard, are poised to influence healthcare significantly. Recently, we put three available LLMs, OpenAI's ChatGPT-3.5, GPT-4.0, and Google's Bard, to the test against a significant Polish medical special-ization licensing exam (PES). The exams cover the scope of completed specialist training, focusing on diagnostic and therapeutic procedures, excluding invasive medical procedures and interven-tions. In our analysis, GPT-4 consistently outperformed the others, ranking first, with and Google Bard and ChatGPT- 3.5 following, respectively. The performance metrics underscore GPT-4's no-table potential in medical applications. Given a score improvement of over 23.5 % between two AI models released just four months apart, clinicians must stay informed and up-to-date about these rapidly evolving tools and their potential applications to clinical practice. Our results provide a snapshot of the current capabilities of these models, highlighting the nuanced performance dif-ferences when confronted with identical questions

Maxillofacial defects, arising from trauma, oncological disease or congenital differences, detrimentally affect everyday life. Prosthetic repair offers the aesthetic and functional reconstruction with the help of materials mimicking natural tissues, among which polymers take unprecedented role. The three-dimensional (3D) printing techniques based on the computer-aided design, where polymers are essential, provide a rapid and cost-effective workflow protocol to perfectly restore patient-specific anatomy for prosthetics. This review discusses the main 3D printing approaches to maxillofacial prostheses fabrication: extrusion and lithography, which are radically preferable to the traditional methods. The main assessment criteria, affording the polymer implementation in 3D printing of prostheses, as well as the characteristics of the key advanced polymers, are considered. The success of the prosthesis is shown to be largely dependent on the retention system, predominantly using polymers in the form of adhesives and osseointegrated implants as a support for the prosthesis. The approaches and technological prospects are also discussed in the context of specific aesthetic restoration on the example of the nasal, auricle and ocular prostheses. 3D printing techniques determine the development of personalized approaches to improve aesthetic and functional effect of prosthetics in patients with maxillofacial defects.

Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1 secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC therapy responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients` blood serum displayed low to undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared to blood serum AH represents the more reliable source for TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimal invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.

Unfortunately in recent years, the global healthcare system has noted a notable increase in the prevalence of obesity and its associated health complications. What is more, one of the significant phenomena is the increasing demand for bariatric procedures among individuals of working age. This trend is pronounced in Poland., due to the increasing number of patients meeting the qualifying criteria for surgery among the group of professionally active and as well as unactive patients. The aim of the study is to characterize alarmingly increasing number of candidates for bariatric procedures among professionally active Poles, who underwent occupational medicine examinations in Poland in 2016-2022 and its strong relationship with cardiovascular co-morbidities (POL-O-CARIA 2022 study). In total, the results of 2,056,861 initial, control and periodic visits as part of the occupational medicine certificate were analyzed. Statistical calculations were performed with the use of IBM SPSS Statistics 25. It was noticed that, there was a consistent rise in the proportion of individuals classified as candidates for bariatric procedures ( increase of 0.3%) alongside a notable decrease in the percentage of individuals maintaining a healthy body weight Moreover, it is imperative to conduct yearly evaluations of the prevalence of obesity and its associated health conditions. This proactive approach is essential in order to adequately equip the healthcare system for addressing the increasing population of obese individuals who are actively engaged in their professions. By doing so, we can strategically implement the most efficient interventions to counteract this trend and ensure optimal health outcomes.

Background. Rectal Magnetic Resonance Imaging (MRI) is a key test in advanced rectal cancer and in the preoperative staging of a lesion suitable for transanal endoscopic surgery (TES). MRI is not operator-dependent, but its results when determining anatomical landmarks are variable. Method. Observational study of inter-observer concordance regarding four diagnostic tests used to establish the anatomical characteristics of rectal lesions: colonoscopy, rectal ultrasound (EUS), rectal MRI, and intraoperative rigid rectoscopy (IRR) in patients scheduled for transanal endoscopic surgery (TES) with curative intent. This inter-observational study assessed the concordance between four expert radiologists regarding the topographic evaluation by means of rectal MRI of lesions under consideration for TES. Results. Fifty-five consecutive rectal tumors were studied. For most of the items, the correlation between IRR and colonoscopy or EUS was generally very good (intraclass correlation coefficient -ICC-)>0.75), although the correlation between MRI and IRR in relation to size by quadrants (ICC=0.092) and location by quadrants (ICC=0.292) was weak. The ICC for the other items obtained excellent correlations: Kappa index >0.80 for all items except for the distance from the peritoneal reflection to the anal verge, where it was merely good (IK=0.606). Conclusions. The anatomical description of rectal lesions that are candidates for TES provided by means of IRR, EUS, colonoscopy and MRI is reliable. The MRI is less reliable, but in the hands of expert radiologists, the anatomical study of rectal lesions is accurate and reproducible.

The Main Protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (cHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FOXP3+ cells was higher in the microenvironment of EBV-related HL, with P values of <0.001, 0.006 and <0.001, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated HL cases (P = 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

Optical “fingerprints” are widely used in chemometrics-assited recognition of samples of different nature. An emerging trend in this area is the transition from obtaining "static" spectral data to reactions occurring over time. The indicator reactions are usually carried out in aqueous solutions; in this study we have developed the reactions that occur in an organic solvent, which makes it possible to recognize fat-soluble samples. In this capacity, we used 5W40, 10W40 and 5W30 motor oils of 4 manufacturers, totally 6 samples. The procedure involved mixing of the dye, sample, and reagents (HNO3, HCl, or t-butyl hydroperoxide) in ethanolic solution in a 96-well plate and measuring absorbance or near-IR fluorescence intensity every several minutes during 20–55 min. The obtained photographic images were processed by linear discriminant analysis (LDA) and k-nearest neighbors algorithm (kNN). The discrimination accuracy was evaluated by using the validation procedure. Reaction of oxidation of a dye with nitric acid allowed to recognize all 6 samples with 100% accuracy by LDA. Merging data of 4 reactions that did not provide complete discrimination ensured an accuracy of 93% by kNN technique. The developed indicator systems have good prospects for the discrimination of other fat-soluble samples. Overall, the results confirm the viability of the kinetic-based discrimination strategy.

Buckground: Although ceftazidime/avibactam (CAZ/AVI) has become important option for treating adults and children, no recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant KPC-2 producing-Klebsiella pneumoniae carrying blaVEB-25 and the use of a customized active surveillance program in conjunction to infection control measures. Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics. Customized molecular surveillance was implemented at hospital level and enhanced infection control measures were taken for early recognition and prevention of outbreak. Detection and identification of blaVEB-25 was performed by next-generation sequencing. Results: That was the first case of a bloodstream infection caused by KPC producing K. pneumoniae that was resistant to CAZ/AVI without the presence of a metalo-β-lactamase in the multiplex PCR platform in a neonate. All 36 additional patients tested (12 in the same NICU and 24 from other hospital departments) carried wild-type blaVEB-1 but they did not harbor blaVEB-25. Conclusion: The emergence of VEB-25 is signal for horizontal transfer of plasmids at hospital facilities and it is of greatest concern for maintaining a sharp vigilance for surveillance of novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and early implementation of infection control measures against antimicrobial resistance.

Coastal areas situated at lower elevations are becoming more vulnerable to flooding as a result of the accelerating global sea level rise. As the sea level rises, so does the groundwater. Barriers designed to shield against marine flooding do not provide protection against flooding caused by rising groundwater. Despite the increasing threat of groundwater flooding, there is limited knowledge about the relationship between sea level rise and groundwater fluctuations. This hinders the ability to adequately consider sea level rise induced groundwater flooding in adaptation initiatives. This study aims to investigate how local groundwater in Juelsminde, Denmark, responds to changes in sea level and to evaluate the predictability of these changes using a machine learning model. The influence of the sea on the shallow groundwater level has been investigated using six groundwater loggers located between 45 and 210 m from the coast. An initial manual analysis of the data revealed a systematic delay in the rise of water levels from the coast to inland areas, with a delay of approximately 15–17 hours per 50 m of distance. Subsequently, a support vector regression model was used to predict groundwater levels 24 hours into the future. This study shows how the groundwater level in Juelsminde is affected by sea level fluctuations. Results suggest a need for increased emphasis on this topic.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious public health issue. Aim of the study was to identify the antimicrobial resistance and accessory genes, the clonal relatedness and the evolution dynamics of selected CRKP isolates recovered in an adult and a pediatric intensive care unit of a tertiary hospital in Greece. Methods: Twenty-four CRKP isolates recovered during 2018-2022 were included in the study. Next-generation sequencing was performed using the Ion Torrent PGM Platform. The identification of the plasmid content, MLST and antimicrobial resistance genes, as well as the comparison of multiple genome alignments and the identification of core genome single-nucleotide polymorphism sites, were performed applying various bioinformatics software. Results: The isolates belonged to eight sequence types 11, 15, 30, 35, 39, 307, 323, and 512. A variety of carbapenemases (KPC, VIM, NDM and OXA-48) and resistance genes were detected. CRKP strains shared visually common genomic regions with the reference strain (NTUH-K2044). ST15, ST323, ST39, and ST11 CRKP isolates presented on average 17, 6, 16 and 866 recombined SNPs, respectively. All isolates belonging to ST15, ST323 and ST39 were classified in distinct phylogenetic branches, while ST11 isolates were assigned to a two-subclade branch. For large CRKP sets, the phylogeny seems to change approximately every seven SNPs. Conclusion: The current study provides insight into the genetic characterization of CRKP isolates in the ICUs of a tertiary hospital. Our results indicate clonal dispersion of ST15, ST323, and ST39 and highly diverged ST11 isolates.

Biogeochemistry of waters is an essential regulator of phytoplankton dynamics, determining the level of species bloom and the change of dominants. The paper investigated the seasonal dynamics of phytoplankton and the nutrient concentration and their ratios in the NE Black Sea in 2017-2021. Two taxonomic groups, diatoms, and coccolithophores, determine seasonal dynamics and significantly contribute to the total phytoplankton biomass. Coccolithophores annually, except in 2020, formed bloom in early June. Large diatoms in summer annually, except in 2019, dominated with biomass exceeding 1000 mg m-3. During the bloom of these taxonomic groups, their contribution to the total phytoplankton biomass exceeded 90%. Each group has characteristic biogeochemical niches in the nitrogen and phosphorus concentrations coordinates. The regulation of the biogeochemistry of water is the position of the seasonal thermocline. With a high-lying and sharp gradient thermocline (the average for five years is 6.87 m), low nitrogen concentrations and a nitrogen-to-phosphorus ratio below the Redfield ratio are created in the upper mixed layer. These conditions are optimal for the dominance of coccolithophores. When the thermocline is deepened (the average for five years is 17.96 m), the phosphorus concentration decreases significantly and the ratio of nitrogen to phosphorus is significantly higher than the Redfield ratio, and these conditions lead to the dominance of large diatoms. The results of experimental studies with nitrogen and phosphorus additives in the natural phytoplankton population confirm the above statements. The addition of phosphorus leads to an increased role of coccolithophores in the total phytoplankton biomass, the addition of nitrogen alone contributes to the growth of large diatoms, and the combined addition of phosphorus and nitrogen in a ratio close to the Redfield ratio leads to the dominance of small diatoms.

The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR=0.56 95%CI 0.35-0.90, Pperm=0.017) and rs2397147 (OR=0.54 95%CI 0.30-0.98, Pperm=0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C×rs17883901-G/G was associated with decreased risk of psoriasis (FDR-adjusted P=0.014), whereas diplotype rs6933870-G/G×rs17883901-G/G (FDR-adjusted P=0.045) showed association with increased disease risk in females. Joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on the risk of psoriasis were observed (Pperm≤0.05). Furthermore, we found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.

The mycotoxin alternariol (AOH) can be found in the food products infected by Alternaria spp. and is considered an endocrine-disruptive mycotoxin. The main mechanism of AOH toxicity is associated with DNA damage and modulation of the inflammation process. Nevertheless, AOH is considered as one of the emerging mycotoxins. In this study we evaluated how AOH might affect a local steroidogenesis process in prostate, in both normal as well as cancer cells. We observed that AOH itself modulates the cell cycle, inflammation and apoptosis rather than steroidogenesis process in prostate cancer cells; however, in the presence of the other steroidogenic agent, the effect is significant. Therefore, this is the first study to report the effect of AOH on local steroidogenesis in normal and prostate cancer cells. We postulate that AOH might modulate the release of the steroid hormones and expression of the key components by interfering with the steroidogenic pathway and might be considered a steroidogenesis-altering agent.

There is a general lack of research involving older lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) people. This systematic review aimed to synthesize Japanese and Swedish qualitative research on LGBTQ people aged 60 years or older. PRISMA guidelines were followed. Japanese and Swedish articles, published in English-language journals, were searched across PsychINFO, Medline, CINAHL, and Sociological Abstracts databases. Additional searches were carried out to include studies written in Japanese or Swedish. There were no papers from Japan, and five from Sweden were reviewed. Four articles were included, including 48 participants aged 60–94 years. We summarized the findings using a deductive thematic synthesis. Two major themes emerged: (a) quality of life, minority joy, and resilience (positive aspects), and (b) experiences of discrimination, stigmatization, and minority stress (negative aspects). The participants described a wish to be acknowledged for their own assets and unique life histories, and to be treated as everyone else. They emphasized the importance of knowledge of LGBTQ issues among nursing staff, so that older LGBTQ people are treated in a competent and affirmative way. The study revealed several important topics for understanding older LGBTQ people’s life circumstances and the severe lack of qualitative studies in Japan and Sweden.

At the beginning of the 21st century, it became obvious that radical changes had taken place in the concept of living matter and, in particular, in the concept of the organization of intracellular space. The accumulated data testify to the essential importance of phase transitions of biopolymers (first of all, intrinsically disordered proteins and RNA) in the spatiotemporal organization of the intracellular space. Of particular interest is the stress-induced reorganization of the intracellular space. Examples of organelles formed in response to stress are nuclear A-bodies and nuclear stress granules. The formation of these organelles is based on LLPS of intrinsically disordered proteins and non-coding RNA. Despite the overlapping composition and similar mechanism of formation, these organelles have different functional activities and physical properties. In this review, we will focus our attention on these MLOs and describe their functions, structure, and mechanism of formation.

Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.

The goal of our study was to examine the effect of regional characteristics of living environment on individual a priori and a posteriori dietary patterns of the Russian population. For the analysis, we used cross-sectional data from the Epidemiology of Cardiovascular Diseases in the Regions of the Russian Federation study of 2013-2014. The sample included 18,054 men and women 25-64 years of age from 12 regions. Based on the frequency of consumption of basic foods, four a posteriori empirical dietary patterns (EDPs), along with an a priori cardioprotective dietary pattern (CPDP) were identified. To describe the regional living environment, 5 regional indices were used. The adherence to the meat-based EDP was directly associated with deterioration of social living conditions and the more northerly location of the region of residence. The probability of CPDP increased with deterioration of social living conditions, an aggravation of demographic crisis, higher industrial development of the region, as well as with a decline in the economic development of the region, income and economic inequality of the population. We detected some gender-dependent differences in associations. The revealed patterns reflect the national dietary preferences of Russians, and regional indices characterize the effect of living environment.

The suppression of natural spaces due to the urban sprawl and increase of the built and agricultural environments has impacted the water resources quality, especially in areas with high population density, as the metropolitan regions. Considering the advance in Brazilian environmental legal framework, the present study aims to verify whether land use has still significantly affected water quality, through a case study in the Stones River watershed, a peri-urban river basin at a metropolitan region, Brazil. Analysis of physical-chemical indicators, collected at several sample points with different land-use (urban areas, commercial forestry, riparian forestry, mixed vegetation, pasture, and sugar cane plantation) at different seasons of the year (dry and rainy) were carried out. As a result, it was verified some statistically significant spatiotemporal effects on the of water quality caused associated to the land-use. In conclusion, in spite of the advances in the Brazilian law, land-use has still significantly affected the water quality, demanding public policies and decisions, so that effective compliance with legal guidelines is ensured.

Nature-based solutions (NbS) - working with and enhancing nature to address societal challenges - are increasingly being featured in climate change adaptation policy and plans. While there is growing evidence that NbS can reduce vulnerability to climate change impacts in general, there is a lack of understanding on the mechanisms through which this can be achieved, particularly in the Global South. To address this, we analyse 85 nature-based interventions in rural areas across the Global South, and factors mediating their effectiveness, based on a systematic map of peer-reviewed studies encompassing a wide diversity of ecosystems, climate impacts, and intervention types. We develop and apply an analytical framework of people’s social-ecological vulnerability to climate change, in terms of six pathways of vulnerability reduction: social and ecological exposure, sensitivity, and adaptive capacity. Most cases (95%) report a reduction in vulnerability, primarily by lowering ecosystem sensitivity to climate impacts (73% of interventions), followed by reducing social sensitivity (52%), reducing ecological exposure (36%), increasing social adaptive capacity (31%), increasing ecological adaptive capacity (19%) and/or reducing social exposure (14%). An analysis of mediating factors shows that social dimensions are equally important as technical factors in NbS to achieving equitable and effective outcomes. Attention to the distinct social and ecological pathways through which vulnerability is reduced helps to harness the multiple benefits of working with nature in a warming world.

E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We have generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-beta (Abeta) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both cerebral cortex and hippocampus at 3-6 months of age. Here we have analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.

Background: Fusarium head blight (FHB) is a serious fungal disease of crop plants due to substantial yield reduction and production of mycotoxins in the infected grains. The breeding progress in increasing resistance with maintaining a high yield is not possible without a thorough examination of the molecular basis of plant immunity responses; Methods: LC-MS based metabolomics approaches powered by three-way ANOVA and differentially accumulated metabolites (DAMs) selection, correlation network and functional enrichment were conducted on grains of resistant and susceptible to FHB genotypes of barley and wheat as well as model grass Brachypodium distachyon (Bd) still poorly known at metabolomic level; Results: We selected common and genotype-specific DAMs in response to F. culmorum inoculation. Immunological reaction at metabolomic level was strongly diversified between resistant and susceptible genotypes. DAMs common for all tested species from porphyrins, flavonoids and phenylpropanoids metabolic pathways were highly correlated and reflects conservativeness in FHB response in Poaceae family. Resistant related DAMs belonged to different structural classes including tryptophan derived metabolites, pirimidines, amino acids proline and serine as well as phenylpropanoids and flavonoids. Physiological response to F. culmorum of Bd was close to barley and wheat genotypes however, metabolomic changes were strongly diversified. Conclusions: Combined targeted and untargeted metabolomics provides comprehensive knowledge about significant elements of plant immunity with potential of being molecular biomarkers of enhance resistance to FHB in grass family. Thorough examination of Bd21 metabolome in juxtaposition with barley and wheat diversified genotypes facilitate their setting as model grass for plant-microbe interaction.

To investigate the dynamics of land surface temperature (LST) in Afghanistan in the period 2000-2021 and to assess the impact of such factors as soil moisture, precipitation, and vegetation coverage on it, remotely sensed soil moisture data from Land Data Assimilation System (FLDAS), precipitation data from Climate Hazards Group Infra-Red Precipitation with Station (CHIRPS), and NDVI and LST from Moderate Resolution Imaging Spectroradiometer (MODIS) were downloaded and correlations between them were analyzed using the regression method. The result shows that the LST in Afghanistan has a slightly decreasing, but insignificant trend during the study period (R=0.2, p-value=0.25), while vegetation coverage, precipitation, and soil moisture had an increasing trend. It was revealed that soil moisture has the highest impact on LST (R=0.7, p-value=0.0007), and the soil moisture, precipitation, and vegetation coverage explain almost 80% of spring (R2=0.73) and summer (R2=0.76) LST variability in Afghanistan. The LST variability analysis done separately for Afghanistan’s rivers subbasins shows that the LST of the Amu Darya subbasin had an upward trend in the study period, while for the Kabul subbasin the trend was downward.

Background: As the only place in a store where all customers must pass through and wait, the checkout lane may be particularly influential over consumer purchases. Because most foods and beverages sold at checkout are unhealthy (e.g., candy/sweets, sugar-sweetened beverages, and salty snacks), policymakers and advocates have expressed growing interest in healthy checkout policies. To understand the extent to which such policies could improve nutrition equity, we as-sessed the prevalence and sociodemographic correlates of purchasing items from checkout. Methods: We assessed self-reported checkout purchasing and sociodemographic characteristics in a national convenience sample of adults (n=10,348) completing an online survey in 2021. Re-sults: Over one-third (36%) of participants reported purchasing foods or drinks from checkout during their last grocery shopping trip. Purchasing items from checkout was more common among men; adults <55 years of age; low-income consumers; Hispanic, non-Hispanic American Indian and Alaska Native, and non-Hispanic Black consumers; those with at least a bachelor’s degree; parents; and consumers diagnosed with type 2 diabetes or pre-diabetes (p-values<0.05). Conclusions: Purchasing foods or beverages from store checkouts is common and more prevalent among low-income and racial and ethnic minority groups. These results suggest that healthy checkout policies have the potential to improve nutrition equity.

Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogramme the tumour microenvironment. However, the antitumour immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication-deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumour potential in vitro in a model of 3D spheroids and in vivo in immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV-derived IFN-g stimulated bone marrow macrophages to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg-infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoural administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumour growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intra-tumoural lymphoid cells isolated from tumours after SFV/IFNg treatment revealed an increase in CD4+ and CD8+ and a decrease in T-reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38 and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumour T-cell response and inhibits myeloid cell infiltration in treated tumours.

This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD) and the severity of these disorders. Toward this end, we have performed effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We have used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of 5 connections, which discriminate patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), fronto-parietal and dorsal attention network (middle frontal gyrus (MFG) corresponding to dorsolateral prefrontal cortex, frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, 4 out of the 5 connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.

In order to better understand the biogeochemical cycle of nitrogen in meromictic lakes, which can serve as a model for past aquatic environments, we measured dissolved concentrations of nitrate, nitrite, ammonium and organic nitrogen in deep (39 m maximal depth) subarctic Lake Svetloe (NW Russia). The lake is a rare type of freshwater meromictic water boy with high concentrations of methane, ferrous iron, manganese and low concentrations of sulfates and sulfides in the monimolimnion. In the oligotrophic mixolimnion, the concentration of mineral forms of nitrogen decreased in summer compared to winter, likely due to phytoplankton bloom. The decomposition of the bulk of organic matter occurs under microaerophilic/anaerobic conditions of the chemocline and accompanied by the accumulation of nitrogen in the form of N-NH4 in the monimonimlion. We revealed a strong relationship between methane and nitrogen cycles in the chemocline and monimolimnion horizons. The nitrate concentrations in Lake Svetloe varied in the range from 9 to 13 μM throughout the water column. This fact is rare for meromictic lakes, where nitrate concentrations up to 13 µM are found in the monimolimnion zone down to the bottom layers. We hypothesize, in accord with available data for other stratified lakes, that under conditions of high concentrations of manganese and ammonium at the boundary of redox conditions and below, anaerobic nitrification with the formation of nitrates occurs. Overall, most of organic matter in Lake Svetloe undergoes biodegradation essentially under microaerophilic/anaerobic conditions of the chemocline and the monimolimnion. Consequently, the manifestation of the biogeochemical nitrogen cycle is expressed in these horizons in the most vivid and complex relationship with other cycles of elements.

Despite recent advances in immune-modulatory drugs, pharmacological therapies have been proven ineffective in severe presentations of multiple sclerosis (MS), including secondary progressive MS. At present, therapeutic interventions' performance is primarily focused on ameliorating symptoms to improve the patient's quality of life. Among complementary treatments, nutrition has been considered a decisive factor to control symptoms and enhance the wellness of MS patients. Although no special diets are associated with MS, the impact of diet and dietary supplements on the course of progressive forms of the disease have been studied during the last years. Fatigue is among the most common and disabling symptoms reported by MS patients. Fatigue has been defined in the Multiple Sclerosis Council for Clinical Practice Guidelines (MSCCPG, 1998) as a "subjective lack of physical and/or mental energy that the individual perceives as an interference with habitual and desired activities". This study aimed to compare the psychometric functioning of the "Fatigue Severity Scale" (FSS) and the "Modified Fatigue Impact Scale" (MFIS) in our sample of people with MS. Specifically, during chronic treatment, the change in these two parameters with two vitamin-rich dietary supplements (Citozym® and Ergozym®) was evaluated. The impact of these nutritional supplements revealed differences in antioxidant and anti-inflammatory parameters between treatment groups with subsequent improvement in fatigue. In conclusion, the results obtained have confirmed the effectiveness of complementary nutritional therapies, evaluated essentially based on hematological biomarkers, through which it is possible to act on disability to improve the quality of life of MS patients.

In recent years cultivated soils have been increasingly supplemented with nutrients that at low doses are necessary for proper plant functioning but become toxic at high doses. New methods are needed to prevent these destructive actions, and for this reason we studied the effects of two elements – Mn treated as a stressor and Se treated as a potential defense in two wheat cultivars. The intensity of stress was manifested in tissue browning and weight reduction and was determined by an increase in lipid peroxidation and quantitative analysis of hydrogen peroxide levels. It was found that the excess of Mn in the substrate caused more intense changes in these indicators in the root system than in the leaves, and that Se presence partly eliminated the stress evoked effects. Moreover, Mn-treatment was accompanied by a greater absorption of this element by the roots, and a reduced uptake of other elements (K, Fe, S, P), with the exception of Ca, an increase in which was observed especially in the additional presence of Se. It was suggested that the rise in Ca level can lead to modification of cell differentiations and may be one of the steps in defense mechanisms. The change in the direction of cell differentiation in the apical part of the root was observed microscopically under Mn stress and was accompanied by a quantitative increase in 5-met C. Based on DNA methylation profiles detected by MSAP we concluded that various types of methylation sites may be activated under Mn treatment in roots.

Background: Tropheryma whipplei is the causative pathogen of Whipple’s disease and other acute and chronic manifestations. Children have been identified as reservoirs of this bacterium especially in low-middle income countries. No information is currently available on the dissemination of T. whipplei in Iran. Therefore, the aim of this study was to investigate the presence of T. whipplei in children with immunodeficiency. Methods: This cross-sectional study was performed from July 2018 to February 2019 in Qom province (central Iran). Stool samples were collected from immuno-compromised children. T. whipplei was tested by SYBR Green and Taq-Man Real-time PCR assays. For confirmation, sequencing of the isolated bacteria was done. Results: One hundred and 30 children with a mean age of 56.7 months were enrolled. Acute lymphocytic leukemia was the most reported immunodeficient disease (77%), followed by non-Hodgkin lymphoma and retinoblastoma. The majority of the children were undergoing chemotherapy during the study. Thirteen (10%) children had T. whipplei DNA in the collected stools. Sequencing results confirmed T. whipplei identification in all the cases. Eight out of 70 (11.4%) children under 5 years old resulted positive. Conclusion: This is the first study showing the circulation of T. whipplei among immunocompromised children in Iran. More epidemiological studies are needed to evaluate the prevalence of this pathogen in different risk groups in Iran and to increase the knowledge of its rare clinical manifestations.

The study aims to identify the difference in communication needs of women giving birth and women during puerperium. An additional goal includes the analysis of the experience and communication needs through the context of a woman's approach to childbirth. The study is a prospective, cross-sectional, self-report survey. 521 women between 5 and 10 days after birth participated in the study. Women perceived information provided by the medical staff as the most helpful aspect of verbal communication both during labour and puerperium. Maintaining eye contact with the medical staff was perceived as the most helpful aspect of non-verbal communication. Women were more satisfied with communication during labour and birth than in the maternity ward and those after non-instrumental childbirth were more satisfied with communication compared to the instrumental birth group. Women perceiving childbirth as the natural, physiological process considered verbal and non-verbal communication during and after childbirth as less helpful than women perceiving birth as more risky and requiring interventions. The results of the study emphasize the importance of verbal and non-verbal communication during birth and puerperium and different communication needs during labour and early postpartum. It also showed that women who perceive labour as a physiological process seem to be less dependent on the communication with the medical staff than women who accept medical interventions during labour and birth as necessary.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

New pharmaceutically acceptable salts of trazodone for the treatment of central nervous system disorders are synthesized and described. Each salt (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthoate) was obtained by two or three different methods leading to the same crystalline form. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthoate were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.

The present study is aimed to determine the predicting role of objective (lifestyle) and subjective factors of middle-aged women’s psycho-emotional health such as their attitude towards parents, attachment and separation types. Women who are overloaded with professional and family roles have high stress level, their indicators of psychological well-being and emotional level decrease when they have to give everyday care to their elderly parents. (2) Methods: Sample consists of 146 women aged 38 to 56 ( =41.1, ó=3.5), married (70.5%) and divorced (29.5%), having children of 14-28 years old; giving everyday care to elderly parents for more than 1.5 yrs. Some live separately (62.3 %), or have to cohabitate with parents (37.7%). All women evaluate their life situation as difficult and manifest signs of high psycho-emotional stress. We used methods adapted for the Russian-speaking sample: getting socio-demographic information, an interview; Attachment style and Interpersonal Guilt Questionnaires (study 1); Psychological Separation Inventory, Purpose-in-Life Test, projective methods of incomplete sentences and metaphors` analysis (study 2), mathematical statistics. (3) Results: A number of factors and indicators of women`s psycho-emotional health decrease in the situation of role overload have been identified. Among the factors there are four main types of women’s attitudes towards parents: strong (anxious), distancing, ambivalent, normative closeness, predicting low indicators of psycho-emotional health: dependence on the others` opinions and feedbacks in making decisions, a lack of meaningfulness of life; reduced sense of control over life are showing the decrease. Anxiety about future and neurotic symptoms (increased demands on oneself, irritability, reduced emotional background) distinguish these respondents. (4) Conclusions: The study confirms that middle-aged Russian women`s psycho-emotional health depends on contextual factors (difficult role-overloaded lifestyle) and factors integrating women`s attitudes towards parents, attachment and separation types. Among the most important risk factors there are a difficult life situation, conflict separation type and gilt.

The main focus of this work is to extend the knowledge about the complexity of issues of oxidative stress. Natural compounds play a serious role in multiple aspects of both human, leading to clear health-promoting effects. This work is focused on the potential application cosmetic formulations containing including but not limited to of clove water and isolated clove oils on their aid in the control of the diseases. The aim of our work was to prepare to evaluate cosmetic formulations containing clove oil, eugenol or new eugenol ester derivative (eugenyl dichloroacetate - EDChA) but also cosmetic formulations containing the aqueous phase obtained after separation of essential oil following the clove buds steam distillation. To evaluate the antioxidants transdermal delivery system, in vitro permeation experiments in a Franz diffusion cell were performed using pig skin. The antioxidative capacity of the cosmetic formulations obtained was determined by the DPPH free radical reduction method. In the next stage, the antioxidant activity (DPPH, ABTS, and Folin–Ciocalteu methods) of the fluid that penetrated through pig skin and of the fluid obtained after skin extraction, were also evaluated. For comparison, studies of cosmetic formulation containing alone dichloroacetic acid (DChAA) were as well carried out. The obtained cosmetic formulations were characterized by of antioxidant activity estimated after 24 hours of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The results of this work contribute to the development of cosmetic formulations with antioxidant potential, emphasizing that the water phases are waste from the process of cloves steam distillation and are not used to prepare cosmetic formulations. The use of waste water from the clove buds steam distillation process is environmentally friendly and not allows us to waste, containing however valuable biologically active compounds (furfural, methyl salicylate, 4-allilofenol, eugenol, α- and β-caryophyllene, eugenyl acetate, β-caryophyllene oxide). Together, these results suggest that cosmetic formulations may be potential drug candidates for chemopreventive, antineoplastic and antimutagenic therapy.

The response of the Cold-Electron Bolometers (CEBs), integrated into a 2-D array of dipole antennas, has been measured by irradiation from YBa$_2$Cu$_3$O$_{7-\delta}$ (YBCO) 50 $\mu$m long Josephson junction into the THz region at frequencies from 0.1 to 0.8 THz. The possibility of controlling the amplitude-frequency characteristic is demonstrated by the external magnetic field in the traveling wave regime of a long Josephson junction. YBCO junction has been formed on the bicrystal Zr$_{1-x}$Y$_x$O$_2$ (YSZ) substrate by magnetron sputtering and etching of the film. CEBs have been fabricated using an Al multilayer structure by a self-aligned shadow evaporation technique on Si substrate. Both receiver and oscillator have been located inside the same cryostat at 0.3K and 2.7K plates, respectively.

The main goal of our work is the revealing of problematic issues related to estimates of the absorption coefficient of colored organic matter in the northern seas from data of the Ocean and Land Color Instrument (OLCI) on the Sentinel-3 satellites. In particular, a comparison of the OLCI standard error estimates ADG443_NN_err., relating to the measurement and retrieval of the geophysical products, with the uncertainties in the real situation of the northern seas, where the natural conditions are extremely unfavorable (first of all, frequent cloudiness, low Sun heights). We conducted a comprehensive multi-sensor study of the uncertainties using various approaches, first at all, directly comparing the data from satellite (OLCI Sentinel-3 and four other ocean color sensors) and field measurements in five sea expeditions 2016-2019, by using the different processing algorithms. Our analysis has shown that the real uncertainties of the final product are significantly higher than the calculated errors of the ADG443_NN_err., which is 100% and ~10%. The main reason for that is the unsatisfactory atmospheric correction. We present the results of the analysis of the different effecting factors (satellite sensors, processing algorithms, use of the other parameters), and formulate the tasks of future work.

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.

Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA) – a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease rodent models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts which characterize the respiratory phenotype of Pompe rodent models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease rodent models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, phrenic and hypoglossal motor nucleus, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle and higher order respiratory control centers. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

Butanol extracts from leaves, twigs and fruits of Elaeagnus rhamnoides (L.) A. Nelson (sea buckthorn, SBT) were fractionated into phenolic and non-polar lipid components. Their chemical composition was analyzed using the Thermo Ultimate 3000RS chromatographic system, equipped with a diode array detector, a corona-charged aerosol detector, and coupled with a (Q-TOF) mass spectrometer. Assuming that an effect on natural microbiotaand host epithelial cells needs to be assessed, regardless of the purpose of using SBT formulations in vivo, the MIC/MBC/MFC of the fractions and reference phytocompounds were screened involving 17 species of Gram-positive and Gram-negative bacteria and Candida species. The impact of the fractions (subMIC) on the important in vivo persistence properties of S. aureus and C. albicans strains was evaluated. Tests for adhesion and biofilm formation on an abiotic surface and the surfaces conditioned with fibrinogen, collagen, plasma or artificial saliva showed the inhibitory activity of the fractions. The effects on FITC-labeled staphylococci adhesion to fibroblasts (HFF-1) and epithelial cells (Caco-2), and on fungal morphogenesis, indicated that SBT extracts have high anti-virulence potential. Cytotoxicity tests (MTT-reduction) on the standard fibroblast cell line showed variable biological safety of the fractions depending on their composition and concentration.

Some novel (phenyl-diazenyl)phenols (3a–g) were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by ¹H nuclear magnetic resonance (NMR), DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC) of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure- activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and in strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.

An analysis of the physical and chemical phenomena accompanying the electrical discharges was carried out, principal factors inactivating microorganisms is studied. Characteristic factors of an electric discharge in cavitation mode providing a synergistic effect when disinfecting water with a discharge and chemical reagents are identified in order of importance. As a result of the integral action of cavitation, the inactivation of bacteria is intensified both due to the emergence of chem-ically active particles and due to local shock waves, acoustic currents and ultraviolet radiation in the area of cavitating bubbles. The similarity of cavitation processes in water systems implemented by underwater electric discharges and with the ultrasound has been experimentally proved. The main advantage of electric discharge cavitation in comparison with ultrasonic one is the wide band of ultrasonic frequencies of radiation inherent in electric discharge, high intensity and power of cav-itation processes, and, accordingly, the possibility of a significant increase in the volume of the disinfected liquid. The study enable better understanding and prediction of the effects that occur during a high-voltage underwater electrical discharge and have a bactericidal effect.

The article aims to present the results of research on anaerobic digestion (AD) of waste wafers (WF - control) and co-substrate system - waste wafers and cheese (WFC - control), combined with digested sewage sludge. The aim of the study was to evaluate the physicochemical parameters of the chitosan/perlite (Ch/P; 3:1) carrier material and to verify its effect on the directions of change of the bacterial microbiome, removal kinetics of organic matter and AD process efficiency. The experiment was conducted in a laboratory, in a periodical mode of operation of bioreactors, under mesophilic conditions. The results of analyses of morphological-dispersive, spectroscopic, adsorption, thermal and microbiological properties confirmed that the tested carrier material can be an excellent option to implement in biotechnological processes, especially in anaerobic digestion. The microstructural properties of the carrier were influenced by both components: perlite determined the development of the specific surface area, while chitosan shaped the porosity of the system. The thermal properties were determined by the less heat-resistant component, present in a threefold higher weight proportion, i.e. chitosan. The evaluation of quantitative and qualitative changes in the genetic diversity of bacterial communities, carried out using Next Generation Sequencing (NGS), showed that the material has a modifying effect on the bacterial microbiome. Amount of bacteria from phyla Actinobacteria, Bacteroidetes, Campilobacterota, Chloroflexi, Euryarchaeota, Planctomycetes, and Proteobacteria decreased while Firmicutes, Synergistetes, and Thermotogae increased during the course of the experiment. The shapes of the FT-IR spectra indicated a dependence of the degradation rate on both the presence of the carrier and the cosubstrate system. Monitoring of the course of AD was carried out by measuring key parameters for the stability of the process: pH, VFA and VFA/TA ratio (volatile fatty acids/total alkalinity). As a result, an increase in the volume of biogas/methane produced, under the influence of the carrier, was recorded for WF-control by 12.05% and for WFC-control by 19.16%. The volume of methane for the WF-control increased from 351.72 m3 Mg-1 VS to 411.14 m3 Mg-1 VS, while for the cosubstrate sample it increased from 476.84 m3 Mg-1 VS to 518.08 m3 Mg-1 VS, confirming the validity of combining the respective cosubstrate with microbial carrier in anaerobic bioreactor.

Archaeometry can help archaeologists in multiple instances, one of the common archaeometric goals are the provenance analyses. Volcanic stones appear frequently in archaeological sites as materials used to build grinding tools like millstones and mortars or as building materials. Petrographic characterization is commonly applied to identify their main mineralogical components. However, provenance of volcanic stones is usually undertaken by comparison with geochemical data from reference outcrops using common descriptive statistical tools such as biplots of chemical elements, and unsupervised multivariate data analysis like principal component analysis (PCA). Recently, the use of supervised classification methods has shown a superior performance in assigning provenance to archaeological samples. However, these methods require the use of reference databases for every possibly provenance class to be able to train the used classification algorithms. The existence of comprehensive collections of published geochemical analyses of igneous rocks enables the use of the supervised approach for provenance determination of volcanic stones. In this paper, the provenance of volcanic grinding tools from two archaeological sites (Iulia Libica, Spain and Sidi Zahruni, Tunisia) is attempted using data from the GEOROC Database through unsupervised and supervised approaches.

The difficulties faced by the society in its goal of reducing mortality and improving the health status during the period of the COVID-19 pandemic showed that it is necessary to develop new approaches in the therapy of infectious diseases, leading to higher treatment efficiency and few side effects. The subject of the present study is the formation and characterization of the proper-ties of stable liposomes loaded with extracts from Bulgarian medicinal plants and monitoring their antiviral action against the human strain of coronavirus OC43 (HCoV-OC43) in vitro. The hydrodynamic diameter and -potential of the liposomes containing each type of payload were determined with DLS and electrokinetics. The encapsulated amount of extracts was evaluated against quercetin and gallic acid by using colourimetric methods. The BALB 3T3 Neutral Red Uptake (NRU) phototoxicity/cytotoxicity assay was used to estimate the safety of the compounds. For assessment of the antiviral activity against HCoV-OC43 of liposomes (Lip) containing medicinal plant extracts, the cytopathic effect inhibition test was used. Measurements of the virucidal activity and the effect on the virus adsorption stage was carried out using the endpoint dilution method, and ∆lgs were calculated by comparison with untreated controls. The estimated photo irritation factors (PIF) for the Lip containing extracts were < 2 which assigns them to the category of non-phototoxic substances. When the extracts were introduced into the liposomes as their carriers, the antiviral activity of the vesicles against the replication of HCoV-OC43 in vitro in-creased by several times compared to their individual activity described in our previous study. The determination of the effect of structures loaded with extracts on the extracellular virions and the stage of their adsorption to sensitive HCT-8 cells proved that the liposomes do not affect directly the viral surface or cell membrane, but only perform a function of carriers of the active substances and the observed result is due solely to the intracellular action of the extracts.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

The paper delves into the critical issue of damage detection within the guy cable of a truss steel mast, a pivotal component in structural integrity. It introduces a model wherein damage manifests as a localized cross-section reduction in a single element of the cable. Employing Discrete Wavelet Transform (DWT), a pioneering methodology, the study scrutinizes the behavior of the affected elements through static structural analyses. Signal decomposition via the Mallat pyramid algorithm facilitates comprehensive examination. Static displacements at the connection point between the cable and the truss mast serve as the measured variables. Through systematic investigation, the paper evaluates the impact of damage size and location, external loading force, and cable tension force on the efficacy of the proposed approach. Utilizing data derived from Finite Element Method (FEM) computations for wavelet analysis the authors substantiate the findings with numerical examples, thus offering valuable insights into damage detection strategies for structural health monitoring and engineering applications.

Training has a significative effect on physiology of blood coagulation both in humans and in horses. Several hemostatic changes have been reported after exercise in the horse but data available are inconclusive. The aim of this study was to investigate the platelet activation and primary platelet-related hemostasis modifications in young untrained Thoroughbred racehorses in the first 4-month timeframe incremental training period in order to improve knowledge on this topic. Twenty-nine clinically healthy, untrained, 2-year-old Thoroughbred racehorses. Never trained Thoroughbreds were followed during their incremental 4-month sprint exercise schedule. Blood collection was performed once a month (T-30, T0, T30, T60, and T90). Platelet aggregation was measured by light transmission aggregometer in response to various agonists: adenosine diphosphate (ADP), collagen and calcium ionophore A23187. Platelet function was evaluated using the Platelet Function Analyzer (PFA-100®) using collagen/ADP and collagen/adrenaline cartridges. Nitrite-nitrate (NOx) plasma concentrations were measured by a colorimetric assay to assess in vivo nitric oxide bioavailability. Platelet activation was investigated also through gene expression analyses (selectin P-SELP, ectonucleotidase CD39-ENTPD1, prostaglandin I2 synthase-PTGIS, endothelial nitric oxide synthase 3-NOS3). Differences among the time points were analyzed and mean±SEM were calculated. Significant modifications were identified compared with T-30 with increase of platelet aggregation (collagen:32.6±4.8 vs 21.6±4.9%; ADP: 35.5±2.0 vs 24.5±3.1%; A23187: 30±4.7 vs 23.8±4%) and a shorter closure time of C-ADP cartridges (75.6±4.4 vs 87.7±3.4 sec) that tended to return to baseline value at T90. NOx concentrations in plasma significantly increased after 30 days of training program compared with baseline. The first long-term training period induce platelet hyperactivity already after 30 days in untrained Thoroughbreds. Regular physical training blunts the negative effects of acute efforts on platelets activation.

Antibiotic Resistance (ABR) is increasing the mortality and morbidity associated with infectious diseases, besides increasing the cost of healthcare, saturating health-system capacity, and adversely affecting food security. Framing an appropriate narrative and engaging local communities through ‘One Health’ approach is essential to complement the top down measures. However, the absence of objective criteria to measure the performance of ABR interventions at community settings make it difficult to mobilize interest and investment for such interventions. An exercise was therefore done to develop an indicator framework for this purpose. An exhaustive list of indicators was developed from experiences gathered through community engagement work in a local panchayat (small administrative area) in Kerala, India, and a consultative process with health, veterinary, environment, and development experts. A prioritization exercise was done, looking at appropriateness, feasibility and validity, by global experts on ABR. A 15-point indicator framework was designed based on the prioritization process. The final set of indicators covers human health, animal health, environment management and Water Sanitation and hygiene (WASH) domains. The indicator framework was piloted in the panchayat(located in Kerala), which attained a score of 34 (maximum 45). The score increased when interventions were implemented to mitigate the ABR drives, indicating the framework is sensitive to change. Simultaneously, the indicator framework was tested in four sites from three other Indian states with different socioeconomic and health profiles, yielding different scores. Those collecting the field data were able to use it with minimal training. To conclude, this indicator framework can help policymakers broadly understand the factors contributing to ABR and measure the performance of interventions they choose to implement in the community

When the formation flying consists of satellites that are independent from each other and forms a virtual synthetic aperture telescope that replaces a single large telescope with all of its optical elements it is required mutual coordination between the satellites with high accuracy in order to achieve good optical observations. In this paper we consider the problem of developing a control system for a tetrahedral satellite formation flying representing a synthetic aperture telescope in the geostationary orbit for high resolution monitoring of fire in the forest area in infrared spectrum. Synthesizing the image with good quality requires to keep the configuration of formation with µm-class accuracy. Study of dynamics of passive uncontrolled motion of formation flying showed a significant deviation of the configuration from the required shape with a high frequency due to the action of gravitational forces. To keep the configuration in the required form with µm accuracy the analysis of efficiency of various controllers was carried out in the process of numerical simulation. The simulation results made it possible to highlight the features of using various approaches to the development of control system for the satellite formation flying representing a synthetic aperture telescope.

Machine learning (ML) techniques can help predict survival among cancer patients and might help with a timely integration in palliative care. We aim to explore the importance of subjective variables self-reported and collected via electronic patient reported outcome measure (ePROM) for survival prediction. A total of 256 advanced cancer patients met the eligible criteria. We analyzed objective variables collected from electronic health records, subjective variables collected via ePROM and all clinical variables combined. We used logistic regression (LR), decision trees, and random forests to predict 1-year mortality. Receiver operating characteristic (ROC) curve - area under the curve (AUC) and the ML models feature importance were analyzed. The performance of all variables for predictions (LR reaches 0.80 [ROC AUC] and 0.72 [F1 Score]) does not improve over the performance of only clinical non-patient reported outcome (non-PRO) variables (LR reaches 0.81 [ROC AUC] and 0.72 [F1 Score]). Our study indicates that patient-reported outcome (PRO) variables, which measure subjective burden, cannot be reliably used to predict survival. Further research in this area is needed to clarify the role of self-reported patient's burden and mortality prediction via ML.

The phototransduction cascade allows the photoreceptor to avoid saturation and retain the ability to detect light over a very wide range of intensities. The main second messenger of the cascade is cGMP and the main regulatory mechanism is calcium feedback, however some experimental data suggest that cAMP may also be involved in the regulation of the phototransduction cascade. For this to be the case, cAMP would have to change on a time scale of seconds. Currently, there are no data on the dynamics of changes in intracellular cAMP levels on this time scale, largely due to the specificity of the sensory modality of photoreceptors, where it is practically impossible to use conventional experimental approaches based on fluorescence methods. In the present work, we used the method of rapid cryofixation of retinal samples after light stimulation and subsequent isolation of outer segment preparations. Levels of cAMP were measured using highly sensitive metabolomics approaches. PKA activity was also measured in these samples by Western blot. We show that when illuminated with near-saturating but still moderate light, cAMP levels rise transiently within approximately the first second and then return to pre-stimulus levels. The increase in cAMP activates PKA, leading to phosphorylation of PKA-specific substrates in frog retinal outer segments.

Gentiopicroside (GPS) is a leading component of several plant species from Gentianaceae botanical family. As a compound with plenty biological activities and a component that is often consumed in dietary supplements and herbal drugs, GPS has an important role in the regulation of physiological processes in humans. Recent studies on the type 2 receptors shed new light on GPS applications showing its agonistic properties that could be meaningful in the future therapeutic strategies of Parkinson’s disease, thyroid disorders or cancer states. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by in vitro and in vivo studies, and to draw attention at the newly discovered role of this bitter-tasting secoiridoid as a type 2 receptor agonist. Thanks to these properties, the research on this substance could be revisited.

The production of oxygenated bio-additives for traditional fuels represents a key challenge due to the depletion of fossil fuels in the next future and their contribution to environmental pollu-tion. In this context, the present study considers the synthesis of different mixtures of 1-hexanol/hexyl hexanoate produced through the catalytic hydrogenation of hexanoic acid, a car-boxylic acid obtainable from the fermentation of a wide variety of waste biomasses. In particu-lar, crude hexanoic acid deriving from the fermentation of grape pomace, an abundant Italian agrifood waste, has been taken into consideration. The reaction was carried out with the com-mercial 5 wt% Re/γ-Al2O3 catalyst, whose acidity allowed the tuning of the reaction selectivity towards the preferential formation of hexyl hexanoate instead of 1-hexanol. As consequence, the tunable composition of the obtained 1-hexanol/hexyl hexanoate mixtures was leveraged for en-gine applications, thus allowing studying each component influence on the Diesel engine per-formances and verifying their synergistic effects. The engine experimental activity highlighted that both 1-hexanol and hexyl hexanoate, as well as their mixtures, can be used in Diesel engine with a commercial Diesel fuel up to high loadings (20 vol%) without altering engine perfor-mances and significantly lowering soot and CO emissions by more than 40%.

Relative contribution of different repair pathways to the radiation-induced DNA damage responses remains a challenging issue of studying the radiation injury endpoints. Comparative manifestation of homologous recombination (HR) after application of different radiation doses greatly determines an overall effectiveness of recovery in dividing cell after irradiation, since HR is an error-free mechanism intended for repair of DNA double strand breaks (DSB) during S/G2 phases of cell cycle. In this article, we present an experimentally observed evidence of dose-dependent shift in relative contribution of HR in human fibroblasts after X-ray exposure at doses 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the radiation dose increase leads to dose-dependent decrease in relative contribution of HR into the entire repair process.

Bi0.5Na0.5TiO3-0.06BaTiO3 (BNT-BT) thin films were prepared by both chemical solution (CSD) and pulsed laser deposition (PLD). The microstructure, dielectric, and ferroelectric properties were investigated. High stability of the dielectric permittivity (∆ɛ/ɛ(150 °C) ≤ ± 15%) over a wide temperature range from room temperature to 300 °C was obtained. Distinctly, the CSD film showed high TCC stability with variation of ± 5% up to 250°C. Furthermore, the CSD film showed an unsaturated ferroelectric hysteresis loop characteristic of the ergodic relaxor phase, however the PLD one exhibited almost saturated loop signature of the coexistence of both ergodic and non-ergodic states. The energy storage properties of the prepared films were determined using the P–E loops obtained at different temperatures. The results showed that these films exhibit stable and improved energy storage density comparable to the ceramic capacitors. Moreover, the CSD film exhibited more rigidity and better energy storage density that exceeds 1.3 J/cm3 under low applied field of 317 KV/cm as well as interesting efficiency in a large temperature range. The obtained results are very promising for energy storage capacitors operating at high temperatures.

There is only a very short reaction time for people to find the best way out of a building in a fire outbreak. Software applications can be used to assist the rapid evacuation of victims; however, this is an arduous task, which requires an understanding of advanced technologies. Since well-known pathway algorithms (such as, Dijkstra, Bellman-Ford and A*) can lead to serious problems over performance, we decided to make use of deep reinforcement learning techniques. A wide range of strategies including a random initialization of replay buffer and transfer learning were assessed in three projects involving schools of different sizes. The results showed the proposal was viable and that in most cases the performance of transfer learning was superior. In addition, the study raised challenges that had to be faced in the future.

Harbor porpoise are typically seen in small groups of 1-3 individuals, with aggregations of 20+ individuals treated as rare events. Since the 1990s, the harbor porpoise population in the Salish Sea has seen a significant recovery, which has led to an increased number of observed aggregations that exceed the more usual small group sizes. By combining the observational data of United States and Canadian research organizations, community scientists, and whale watch captains or naturalists, we demonstrate that harbor porpoise aggregations appear to be more common than previously known, with 160 aggregations documented in 2022 alone. Behavioral data also indicated that foraging behaviors were common and social behaviors, like mating, were seen more often during these encounters compared to small groups. Other behaviors that are considered to be rare or unknown, were also observed during these encounters, including cooperative foraging and vessel approach. These aggregations are likely important foraging and social gatherings for harbor porpoises. This holistic approach integrating data from two countries and multiple sources provides an ecosystem level assessment that more effectively reflects the habitat use of harbor porpoise in this region that do not recognize the socio-political boundaries imposed upon the natural world.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the placenta), preservation techniques, decellularization status, design, and clinical application have not been fully evaluated. This re-view provides an overview of wound healing and placental-derived biomaterials, summarizes the clinical results of placental-derived scaffolds in wound healing, and suggests directions for future work.