Earth’s extinction crisis is escalating, and threat classification schemes are increasingly important for assessing which human activities are the most prominent drivers of species declines. However, a quantitative understanding of the conservation responses needed to abate threatening processes, and avoid species extinctions, is often lacking. Here, we provide a threat abatement framework which groups threats based on the shared conservation goal of the actions needed to abate their impact. We apply this framework to Australia’s threatened species to quantify the relative importance of achieving different conservation response goals. Our analysis shows the most important conservation responses across Australia are habitat retention and restoration, due to the combined impact of threatening processes causing habitat destruction and degradation (e.g. logging, mining, urbanisation and agriculture), which affects the majority (86%) of Australia’s threatened species and the effective control of invasive species (82%). Most species also require conservation responses focussed on improved fire management (66%). We show that implementing responses in isolation will be inadequate for abating species extinctions as almost all species (89%) require multiple, integrated management responses to redress their threats. We also acknowledge that already small and potentially genetically compromised taxa may require more direct interventions (e.g. captive insurance populations or genetic rescue). Our analysis highlights the necessity of addressing multiple threats at appropriate geographic scales across Australia. Our threat abatement framework ensures that core conservation actions can be identified and aid recovery of threatened species, and can be applied to other geographic regions and conservation contexts.

There is evidence that optimal nutrition is fundamental to human health and in the prevention of non-communicable diseases (NCDs) later in adult life. The identification, production and consumption of functional foods worldwide can increase health benefits for all who can access and afford such foods subject to advice from nutritionists. Recent meetings organized by the health agencies, give a crucial opportunity to make nutrition, a central part of the post-2015 sustainable human and agricultural development agenda. The aim of discussions in these meetings was to provide functional crops and foods to achieve optimal health by prevention of NCDs. It is possible that these efforts might ensure that the goals and targets set in the agenda are adequate to address the many challenges of global undernutrition as well as obesity which are major risk factors of NCDs. In many developing and middle income countries, food security provided by the governments, in one sense understandably, gave least consideration to functional foods supply and the prevention of obesity and metabolic syndrome, resulting in to emergence of NCDs. The Thailand Declaration reiterates that commitments to eradicate hunger and undernutrition as well as over-nutrition, and to increase investments in effective interventions; designers foods and designers crops. However, in planning coherent policies, our past experience on rapidly absorbed, energy-rich processed foods should be taken in to account while developing sustainable food systems. The food industry should be educated to exploit the expertise of food scientists and health professionals in designing functional foods taking cognizance of manufacturing and processing. Similarly, agriculture scientists may be actively involved in educating farmers so as to grow cash crops providing functional foods. The aim should be to achieve an increase in the availability of functional foods to an extent, or by a policy, by which such foods are available to poors, at affordable cost to prevent hunger and undernutrition and related diseases as well as NCDs. In addition our efforts might help in developing an international consensus on how to approach the development of new designer foods by farmers and food industry to produce low glycemic index foods. Such efforts may establish an international framework for the prevention of NCDs, so that human susceptibility to these diseases is substantially diminished.

The role that aquatic aerosols might play in inter-ecosystem exchange in freshwater riparian environments has largely been understudied. In these environments, where freshwater streams are used both as drinking water and for treated waste disposal, water features like waterfalls, downed trees, and increased streamflow can serve as bioaerosol producers. Such water features could have an important role in the bacterial colonization of surrounding surfaces, including the riparian phyllosphere. In this study, we explore the influence of a freshwater stream’s bacterial community composition and micropollution on riparian maple leaves exposed to bioaerosols produced from the stream. Using culture-based and non-culture-based techniques, we compared phylloplane microbial communities in riparian zones, adjacent non-riparian forested zones, and the surface waters of the stream. In this system, riparian zone maple leaf surfaces had higher bacterial counts than non-riparian zone trees. Using metagenomic profiling of the 16S rRNA gene, we found that, while microbial communities on leaves in both riparian zone and forested sites were diverse, riparian zone bacterial communities were significantly more diverse. In addition, we found that riparian leaf bacterial communities shared more amplicon sequence variants (ASVs) with stream bacterial communities than forest leaves, indicating that the riparian zone phyllosphere is likely influenced by bioaerosols produced from water surfaces.

Background: Patients undergoing brain tumor resection experience changes to their neurocognitive abilities, many of which can be difficult to predict. We hypothesized that changes in brain connectivity could predict changes in neurocognitive functioning, demonstrating the potential for brain connectivity aware surgical planning to provide enhanced outcomes for patients. Methods: Patients underwent functional and diffusion MR scanning and neuropsychological testing before tumor resection and two weeks post-resection. Using this functional and diffusion imaging, we measured changes in the topology of the functional and structural graph networks, respectively. From the neuropsychological testing scores, we derived a composite score that describes a patient’s overall level of neurocognitive functioning. We then used a multiple linear regression model to test if structural and functional connectivity measures could predict changes in composite scores. Results: Twenty-one subjects completed imaging and neuropsychological evaluation both before and after surgery. The multiple linear regression model showed that changes in functional local efficiency were inversely correlated with changes in composite score (p

Combined radiation with hemorrhage (combined injury, CI), exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ- radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4-5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4-5 h and continued to decrease them until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin and hematocrit on days 7 and 15 compared to RI, whereas Hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a biomarker within 2 days post-CI and RBC depletion after 3 days post-CI.

Fire blight, caused by the plant-pathogenic bacterium Erwinia amylovora, is a highly contagious and difficult-to-control disease due to the efficient dissemination, survival, and scarcity of effective control methods. Copper and antibiotics are the most used treatments but pose environmental and human health risks. Bacteriophages (phages) constitute an ecological, safe, and sustainable fire blight control alternative. The goal of this study was to search for specific E. amylovora phages from plant material, soil, and water samples in Mediterranean environments. A collection of phages able to specifically infect and lyse E. amylovora strains was generated from former fire blight-affected orchards in Eastern Spain. Following in vitro characterization, assays on immature fruit revealed that preventively applying some of the phages or their combinations delayed the onset of fire blight symptoms and reduced the disease severity, suggesting their biocontrol potential in Spain and other countries. Morphological and molecular characterization of the selected E. amylovora phages classified them as members of the class Caudoviricetes (former Myoviridae family) and genus Kolesnikvirus. This study reveals Mediterranean settings as plausible sources of E. amylovora-specific bacteriophages, and provides the first effective European phage cocktails in plant material for the development of sustainable fire blight management measures.

Pituitary adenomas are benign brain tumors that pose a heavy burden on patients worldwide. However, the local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.

Babesia microti (B. microti), is a tick-transmitted protozoan parasite that infects red blood cells. It is the primary cause of human babesiosis in the US. It is also considered an emerging pathogen that continues to expand in terms of both numbers of cases and geograpical range. The severity of babesiosis can range from asymptomatic to fatal. Nevertheless, the mechanisms important for resolution of infection versus pathology remain largely unknown. In the current study we used a mouse model to evaluate factors important in protection from reinfection with B. microti following the clearance of a primary infection. Both B cell and CD4 T cell deficient mice failed to completely eliminate parasitemia 36 days post-infection following primary challenge. In the recall mouse model of infection, wild type or specific gene deleted mice were reinfected with the same strain of B. microti parasites 30-36 days after the initital primary infection, and the development of parasitemia was evaluated. Our results show that wild type mice were protected from reinfection with B. microti. In contrast, B cell and CD4 T cell deficient mice were only modestly impaired in their ability to protect against rechallenge as protection was more similar to reinfected wild type mice than naïve mice. However, one reinfected B cell deficient mice developed parasitemia levels similar to those observed in primary infection. Other factors including IFN-γ, inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88 important for signling via IL-18 and IL-1 had no effect on rechallenge. Thus our study shows that infection with B. microti confers at least short term protection against rechallenge with the same parasite strain. Our data show that CD4 T cells make an important contribution to both primary and rechallenge infection with B. microti. They also suggest that antibody might play an important role in protection against reinfection or persistent infection. However, overall our results Our results suggest that no one aspect of the immune system is solely responsible for adequate protection against reinfection with B. microti.

The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse molecular frameworks. Specific examples are carefully selected to illustrate the distinct contributions of these functional groups to general strategies for molecular design, modulation of biological activities, computational modeling, and structure-activity relationship studies. An extensive literature search was conducted across three databases, including Pub-Med, Google Scholar, and Scifinder, enabling us to create one of the most comprehensive overviews of how oximes and oxime ethers impact antitumor activities within a wide range of structural frameworks. This search focused on various combinations of keywords or their synonyms, related to the anticancer activity of oximes and oxime ethers, structure-activity relationships, mechanism of action, as well as molecular dynamics and docking studies. Each article was evaluated based on its scientific merit and the depth of the study, resulting in 268 cited references and more than 336 illustrative chemical structures carefully selected to support this analysis. As many previous reviews focus on one subclass of this extensive family of compounds, this report represents one of the rare and fully comprehensive assessments of the anti-cancer potential of this group of molecules across diverse molecular scaffolds.

New Schiff base ofN'-((E)-3,3-diphenyl-2,3-dihydro-1H-inden-1-ylidene)-2-((Z)-2-oxoindolin-3-ylidene)hydrazine-1-carbothiohydrazide (HL) and its Co(II),Ni(II), Fe(III), Cu(II), Cd(II), Zn(II) and Mn(II) complexes were created, isolated, and characterized by analytical analysis in good yields of 60 to 90%, UV–Vis, magnetic measurements, molar conductivity, and FT-IR. Additionally, mass spectrometry was used to examine the new ligand complexes' structural characteristics.1H NMR spectroscopy and elemental analysis. Depending on the electronic spectra and magnetic susceptibility measurements, these complexes are predicted to have octahedral molecular geometry. As an example, the quantum chemical properties, bond lengths, and bond angles were discussed. The structural formula for the examined ligand was improved using the Gaussian09 tool. The DFT/B3LYP method was used to calculate the energy gaps and other crucial theoretical features. The prepared hydrazine ligand complexes Co (II), Ni (II), Fe (III), Cu (II), Cd (II), Zn (II) and Mn (II) complexes were evaluated for its antimicrobial properties. As antimicrobial agents, it was found that the organic ligand was less biologically active than the targeted complexes. Gram positive bacteria (3ty7-Staphylococcus), Gram negative bacteria (3t88-Escherichia coli), and fungi (5k04-Candida albicans) all have crystal structures that interact well with the chemicals in the title, according to molecular docking.

BACKGROUND: Pre-marital sex is a sexual interest practiced by people who are yet to get married and has ended up being accepted specifically in western countries. Sex before marriage is sexual behavior engaged in by single people. In the past, having sex before getting married is seen as a moral dilemma that many cultures forbade and that many people regarded to be sin in many religions, although it has gained wider acceptance across the board. OBJECTIVES: This study was carried out to determine the perception, practices, and factors associated with pre-marital sex, courtship, and its influences among Osun State University Undergraduates, Osogbo, Osun State. METHODOLOGY: The study was a descriptive study, and respondents were selected using multi-stage sampling technique. Students of Osun State University, Osogbo main campus form the population of the study and its sample size was calculated using Leslie Kish’s formula. A total of 387 responses were validated from the survey. The instrument for data collection was a self-administered semi-structured questionnaire consisting of four sections. The data obtained were collated, examined for completion, coded, imputed, and analyzed using SPSS v21. RESULTS: The mean age of the respondents was between 19.19±2.17, and the majority were between 18 – 24 years. About 52% of the respondents show a positive perception of premarital sex and courtship. Also, in the practice of courtship majority (88.3%) of the respondents think those that go around together are courting and from the responses obtained and analyzed from the factors leading to pre-marital sex, the findings revealed that peer pressure (90.4%), Internet (86.7%), pornography (83.9%) and drugs (82.9%) are the leading factors which contribute to pre-marital sex among undergraduates. CONCLUSION: The study hereby recommends that Parents should as a matter of responsibility monitor and pays regular visits to their children in the universities and provide them with materials that will make them stay comfortable for them not to fall victim to peer pressure.Pre-marital sex is a practice that should be avoided by undergraduate students, though most students consider courtship as a normal practice, it is still used as a normal factor that leads them to practice pre-marital sex.

Canistel (Pouteria campechiana (Kunth) Baehni) (yellow sapote, canistel). Originally from Mexico, the fruit is edible, and the tree is used as an ornamental and medicinal plant. Descriptive studies were carried out with the objective of morphologically characterizing the fruits and leaves of trees located in different regions of Mexico to select outstanding specimens and propose their massive reproduction. The trees were selected in three zones. In zone 2 from flower anthesis to harvest 11 months, fruits with 3 seeds, greater weight (180 to 330 g) and quantity of pulp (198.88 g), subglobose shape, total soluble solids 33 %. The fruits of zone 1 at harvest 8 months and zone 3 took 9 months to be harvested, in the rest of the characteristics evaluated were exceeded by the fruits of zone 2. To characterize the canistel (P. campechiana) leaf and identify accessions or cultivars, the three main variables, according to the principal component analysis were: leaf area, perimeter, and minor diameter. The three zones where canistel fruits and leaves were characterized are important and can be recommended for propagation in zones with favorable climatic conditions for fruiting in tropical and subtropical regions of Mexico.

Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared, and characterized. An analysis by Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. The morphology of the prepared nanocomposites studied by field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) shows significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revels that the functionalized CNTs affects strongly the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of prepared nanocomposites to inhibit the growth of the fungus Candida albicans, and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli was evaluated. A moderated antifungal and antibacterial capacity of the prepared nanocomposites was determined.

The role of mesenchymal-to-endothelial transition in the angiogenic response is controversial. Toward this, the present study aimed to determine if fibroblasts contribute to angiogenesis. Endothelial differentiation of fibroblasts was induced by culturing MRC-5 cells (human fetal lung fibroblast cells) on top of Matrigel hydrogel or embedded inside the hydrogel. The formation of ca-pillary-like networks in response to angiogenic signals was observed. The tube formation occurs quickly and can be visualized us-ing a phase-contrast inverted microscope, and/or the cells can be treated with DAPI before the assay and tubes can be visualized through fluorescence or confocal microscopy. Furthermore, fibroblasts cultured in a higher concentration invaded the Matrigel hydrogel and formed stem-cell-like spheroids. These spheroids embedded in matrigel matrices of varying densities sprouted to form 3D connective-tissue networks. Collectively, our results highlight the endothelial differentiation capacity of human lung fibroblasts. The results obtained in this work may have an impact on the search for alternative cell sources for vascular tissue engineering and the overcome of obstacles to vascularization of autologous tissue-engineered constructs and the production of functional grafts for clinical use.

Rabies, caused by the rabies virus (RABV), remains a significant public health issue in the Philippines despite efforts to control it. To eliminate rabies by 2030, effective surveillance strategies are crucial. In this study, we examined RABV evolution and phylodynamics in the Davao Region using genome sequences from Davao City and nearby provinces. We adapted the RABV ARTIC Protocol for Oxford Nanopore High-Throughput Sequencing to optimize workflow efficiency under limited resources. Comparing new virus samples collected from June 2019 to June 2021 (n=38) with baseline samples from June 2018 to May 2019 (n=49), new sub-clades were observed in the phylogenetic tree, suggesting divergence from older variants that were previously undetected. Most of the new viruses belonged to the Asian SEA4_A1.1.1 lineage, but new (SEA4_B1 and SEA4_B1.1) and emerging (SEA4_B1.1_E1) lineages that have never been reported in the Philippines were also identified. The baseline study reported phylogeographic clustering of RABV isolates from the same areas. However, this pattern was disrupted in the current biosurveillance, with variants detected in areas outside the original cluster. Furthermore, our findings revealed significant transmission routes between Davao City and neighboring provinces, contrasting with the predominantly intra-city transmission observed in the baseline study. These results underscore the need for ongoing and timely genomic surveillance to monitor genetic diversity changes and the emergence of novel strains, as well as to track alterations in transmission pathways. Implementing cost-effective next generation sequencing workflows will facilitate the integration of genomic surveillance into rabies control programs, particularly in resource-limited settings. Collaborations between different sectors can empower local laboratories and experts in genomic technologies and analysis.

Background: Understanding the factors that influence the market entry, exit, and stability of community pharmacies (i.e., market dynamics) is important for stakeholders ranging from patients to health policymakers and small business owners to large corporate institutions. The purpose of this article is to provide an update to a 15-year ecological comparison for the market dynamics of Minnesota community pharmacies from 2002 to 2017 [1]. Objectives: The first objective was to update the 15-year study [1] by describing the market dynamics of community pharmacies for each county in the state of Minnesota every five years over a 20-year period (i.e., 2002-2022). The second objective was to update the 15-year study by describing the number and proportion of community pharmacies for each county in the state of Minnesota every five years over a 20-year period (i.e., 2002-2022) by (1) ‘Business Organization Structure’ and (2) ‘Pharmacy Type.’ The third and fourth objectives were new for the 2022 study. In response to evolutionary trends in the pharmacy market, objective three described the number of Minnesota licensed pharmacies located in-state and out-of-state between 2002 and 2022. Objective four described the primary type of service provided by licensed pharmacies categorized as out-of-state in 2002 and in 2022. Methods: Data were obtained from the Minnesota Board of Pharmacy, US Census Bureau, and Minnesota State Demographic Center for 2002, 2007, 2012, 2017, and 2022. Descriptive statistics were used to tabulate and summarize the findings and test associations between study variables. Results: Over the 20-year study period, the total number of community pharmacies in Minnesota remained steady. Findings for 2022 were similar to those for 2017 regarding the effects of population density and metropolitan designation on the market dynamics of community pharmacies and regarding the organizational structures and types of pharmacies. The findings revealed significant growth in the number of proportion of pharmacies licensed in Minnesota that were located out-of-state. In 2002, there were 283 of these pharmacies (19% of the total). By 2022, this grew to 960 (46% of the total). Over that 20-year period, the number of mail order and medical supply service pharmacies rose from 196 to 413. The number of specialty pharmacy distributors rose from 37 to 230 and the number of compounding pharmacies rose from 33 to 202. Discussion: The findings confirmed the shift over the past 20 years from traditional retail convenience models to healthcare access models based on population health metrics. National scalability was another detected shift in order to have profitable margins for some services and was feasible due to advances in technologies. Conclusion: The findings showed that community pharmacy distribution in Minnesota’s 87 counties shifted between 2002 and 2022 from traditional retail convenience models to healthcare access models based on population health metrics and to nationally scalable models based on economic pressures. This signals the need for not only new approaches for tracking community pharmacy market dynamics but also adjustments by community pharmacies to remain relevant in a new environment of patient care services.

In the present work, a comparative evaluation of an MBBR unit performance was carried out for the following cases: when adding 3D-printed biocarriers fabricated with 13X and bentonite, when using K1 commercial biocarriers and when not adding biocarriers at all. For the evaluation of the MBBR efficiency, various physicochemical parameters were measured, while static light scattering and optical microscopy observations were additionally used. Finally, biofilm extracted from the biocarriers was evaluated. The findings suggest that there is an optimal biodegradation of the organic load in all MBBR units. The nitrification and denitrification process were improved at the 3D MBBR as compared to the control MBBR and MBBR K1. The dry mass of the biofilm in the 3D-printed biocarriers was two orders of magnitude larger than the one in the K1 biocarriers. What is more, in the K1 biocarriers the mass of the biofilm varied in relation to time, due to the fact that it could not be kept inside the holes, something that was not observed to happen with the 3D-printed biocarriers. Finally, it was observed, mostly in the 3D MBBR and less in the K1 MBBR, that the growth of nitrifying bacteria and heterotrophs inside the units increased the biomass production in the form of SMP, which in turn favored the adhesion of biomass on the surface of biocarriers.

Traditional medicine is one of the main bases for studying and discovering natural sources of phytometabolites with antiviral properties. This research aims to demonstrate that the medicinal plants used as a treatment of viral diseases in the La Libertad region have, in fact, antiviral ac-tivity. The study evaluated the ethnobotany of the 8 most widely used medicinal plants in the region (Azadirachta indica A. Juss. “paraíso”, Caesalpinia spinosa (Molina) Kuntze “tara”, Citrus limon (L.) Osbeck “limón”, Clinopodium pulchellum (Kunth) Govaerts “panizara”, Cordia lutea Lam. “overo”, Ocimum basilicum L. “albahaca”, Schinus molle L. “molle”, and Taraxacum campylodes G.E. Haglund “diente de león”). The phytometabolites responsible for the antiviral activity were identified by LC-MS and evaluated in silico against the viral proteins NS2B/NS3 (DENV-2), NS5B (HCV), and ICP27 (HSV-1) using molecular docking in Autodock Vina and UCSF Chimera. The presence of five polyphenols (chlorogenic acid, gallic acid, caffeic acid, rosmarinic acid, and rutin) was found and, in the in silico test, the antiviral activity of chlorogenic acid stood out against DENV-2 and HCV, rutin against HCV and HSV-1, rosmarinic acid against DENV-2 and HCV. Therefore, it is verified that the medicinal plants studied have antiviral activity, which supports their use in traditional medicine

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein-ligand docking.

Evidence that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible children has mounted for more than a decade. Evidence is diverse, including extensive work with laboratory animals, otherwise unexplained associations, factors associated with the metabolism of acetaminophen, and some limited studies in humans. Although evidence has reached an overwhelming level and has been reviewed in detail recently, some controversy remains. In this narrative review, some of those controversies are evaluated. First, the associations through time between acetaminophen use and the prevalence of neurodevelopmental disorders are considered. A systematic review reveals that the use of acetaminophen in the pediatric population was never tracked carefully, but historical events that affected use of the drug were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Second, problems with exclusive reliance on results from meta-analyses of large datasets and from studies involving small time frames of drug exposure are reviewed. Third, the potential bias in a study designed to separate the role of vaccines and acetaminophen in the induction of autism spectrum disorder (Autism 2008;12:293-307) is carefully evaluated. Finally, evidence demonstrating why some children are susceptible to acetaminophen-induced neurodevelopmental injury is examined. It is concluded that, at least among the factors considered, there is no valid rationale for controversy regarding the conclusion that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible babies and small children.

Background: All Payer Claims Databases (APCD) are a rich source of health information, however, race and ethnicity (R&E) data are largely missing. Bayesian Improved Surname Geocoding (BISG) is a common R&E imputation method, yet, validation of BISG in APCDs is lacking. We used the BISG to impute missing R&E in the Oregon APCD. Methods: BISG imputed R&E for Asian Pacific Islanders (API), Blacks, Hispanics and Whites were contrasted to the gold standard (vital statistics) and sensitivity and specificity improvements were assessed. Logistic regression examined whether missing R&E was random across patient characteristics. Results: Among 85,857 individuals in the study, 32.1% (n=27,594) had missing R&E. Missing R&E was not randomly distributed. There were higher odds of missingness among males, Whites, those age 65 and older, and commercially insured individuals. Differences in the percent missing were also found by co-morbid conditions and mortality causes. Imputing the missing R&E with BISG method improved the sensitivity to identify White, Black, API, and Hispanics. Conclusions: APCDs can benefit from enhancing missing R&E with BISG imputation to perform more robust population-health level analyses and identify inequities according to R&E without losing power or dropping non-random records with missing R&E data.

Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of about 10,000 different soluble and membrane proteins in humans. It involves co- or post-translational targeting of precursor polypeptides to the ER and their subsequent membrane insertion or translocation. So far, three pathways for ER targeting of precursor polypeptides plus four pathways for ER targeting of mRNAs were described. Typically, these pathways deliver their substrates to the Sec61 polypeptide-conducting channel in the ER membrane. Next, the precursor polypeptides are inserted into the ER membrane or translocated into the ER lumen, which may involve auxiliary translocation components, such as the TRAP and Sec62/Sec63 complexes, or auxiliary membrane protein insertases, such as EMC and the TMCO1 complex. Recently, the PEX19/PEX3-dependent pathway, which has a well-known function in targeting and inserting various peroxisomal membrane proteins into pre-existent peroxisomal membranes, was also found to act in targeting and, putatively, inserting monotopic hairpin proteins into the ER. These either remain in the ER as resident ER membrane proteins or are pinched off from the ER as components of new lipid droplets. Therefore, the question arose if this pathway may play a more general role in ER protein targeting, i.e. represents a fourth pathway for ER targeting of precursor polypeptides. Thus, we addressed the client spectrum of the PEX19/PEX3-dependent pathway in both PEX3-depleted HeLa cells and PEX3-deficient Zellweger patient fibroblasts by an established approach, which involves label-free quantitative mass spectrometry of the total proteome of depleted or deficient cells and differential protein abundance analysis. The negatively affected proteins included twelve peroxisomal proteins and two hairpin proteins of the ER, thus confirming two previously identified classes of putative PEX19/PEX3-clients in human cells. Interestingly, fourteen collagen-related proteins with signal peptides or N-terminal transmembrane helices and belonging to the secretory pathway were also negatively affected by PEX3-deficiency, which may suggest compromised collagen biogenesis as a hitherto unknown contributor to organ failures in the respective Zellweger patients.

As a consequence of intense industrialization in the last few decades, the amount of agro-industrial wastes has increasing, where new forms of valorization are crucial. In this work, 5 residual biomasses from Maranhão (Brazil) were investigted as supports for immobilization of lipase from Thermomyces lanuginosus (TLL). The new biocatalysts BM-TLL (babaçu mesocarp) and RH-TLL (rice husk) showed immobilization efficiencies >98% and hydrolytic activities of 5,331 U.g-1 and 4.608 U. g-1 respectively against 142 U. g-1 by Lipozyme® TL IM. High esterification activities were also found, with 141.4 U.g-1 and 396.4 U.g-1 from BM-TLL and RH-TLL against 113.5 U.g-1 by TL IM. Results of porosimetry, SEM and BET demonstrated BM and RH supports are mesoporous materials with large hydrophobic area, allowing a mixture of hydrophobic adsorption and confinement, resulting in hyperactivation of TLL. These biocatalysts were applied in the production of hexyl laurate, where RH-TLL was able to generate 94% conversion in 4 h. Desorption with Triton X-100 and NaCl confirmed that new biocatalysts were more efficient with 5 times less protein than commercial TL IM. All results demonstrated that residual biomass was able to produce robust and stable biocatalysts containing immobilized TLL with better results than commercial preparations.

Coxiella burnetii (Derrick) Philip, the causative agent of Q fever, is mainly transmitted by aerosols, but ticks can also be a source of infection. Transstadial and transovarical transmission of C. burnetii by Hyalomma lusitanicum (Koch) has been suggested. There is a close relationship between this tick species, wild animals and C. burnetii but the transmission in a natural environment has not been demonstrated. In this study, we collected 80 engorged nymphs of H. lusitanicum from red deer and wild rabbits. They molt to adults under laboratory conditions and we feed them artificially through silicone membranes after a preconditioning period. C. burnetii DNA was tested in ticks, blood and feces samples using real-time PCR. The pathogen was found in 36.25% of fed adults demonstrating that transstadial transmission from nymph to adult occurs in nature. The presence of DNA in the 60% of blood samples confirms that adults transmit the bacteria during feeding. Further studied are needed about co-feeding and other possible transmission routes to define the role of this tick species in the cycle of C. burnetii.

The AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN (AHL) gene family encodes embryophyte-specific nuclear proteins with DNA binding activity. They modulate gene expression and affect various developmental processes in plants. We identify AHL18 (At3G60870) as a developmental modulator of root system architecture and growth. AHL18 regulates the length of the proliferation domain and number of dividing cells in the root apical meristem and thereby, cell production. Both primary root growth and lateral root development respond according to AHL18 transcription level. The ahl18 knock-out plants show reduced root systems due to a shorter primary root and a lower number of lateral roots. This change results from a higher number of arrested and non-developing lateral root primordia (LRP) rather than from decreased initiation. Overexpression of AHL18 results in a more extensive root system, longer primary roots, and increased density of lateral root initiation events. Formation of lateral roots is affected during the initiation of LRP and later development. AHL18 regulate root apical meristem activity, lateral root initiation and emergence, which is in accord with localization of its expression.

This paper aims in studying the effect of vermicompost on soil and growth of the plant Sesamum indicum L. by measuring the its various growth and yield components. For this purpose, a mixture of textile mill sludge, cow dung and saw dust have been mixed in different ratios to produce vermicompost by using the earthworm Perionyx excavates and was compared with inorganic (NPK) and organic fertilizer (FYM). The results of soil quality revealed that the porosity, water holding capacity (WHC), cation exchange capacity (CEC) and occurrence of macronutrients were significantly increased and the particle density were decreased in treatment with 100% vermicompost (VC) followed by soil treated with 50% VC + 50% NPK, on contrary, reduction in porosity, WHC, CEC were noted in NPK treated plots. The effect of vermicompost on plant growth components (root, shoot, leaf area index, branch, DMP) and yield components (pod number, weight, length, seed weight, number of seed, seed yield) were significantly higher in the plots treated with 50% VC + 50% NPK followed by 100% vermicompost than the plots treated only with FYM and NPK. The significant growth upon using vermicompost was accounted by its nutrients composition over other fertilizers.

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal-end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices remains a critical challenge, particularly in a way suitable for large scale adoption. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3 ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Monitoring coffee quality as a means of detecting and preventing economically motivated fraud is an important aspect of international commerce today. Therefore, there is a compelling need for rapid high throughput validated analytical techniques such as quantitative proton NMR spectroscopy for screening and authenticity testing. For this reason, we sought to validate an NMR spectroscopic method for routine screening of coffee for quality and authenticity. A factorial experimental design was used to investigate the influence of NMR device, extraction time and nature of coffee on the content of caffeine, 16-O-methylcafestol (OMC), kahweol, furfuryl alcohol and 5-hydroxymethylfurfural (HMF) in coffee. The method was successfully validated for specificity, selectivity, sensitivity and linearity of detector response. The proposed method produced satisfactory precision for all analytes in roasted coffee, except for kahweol in canephora (robusta) coffee. The proposed validated method may be used for routine screening of roasted coffee for quality and authenticity control, as its applicability was demonstrated during the recent OPSON VIII Europol-Interpol operation on coffee fraud control.

Aqueous and ethanolic extracts of Hibiscus sabdariffa were spray-drying using maltodextrin (MD) and gum arabic (GA) as carriers agents. An experimental design Taguchi L8 with seven variables was implemented. Physicochemical properties in the encapsulates were evaluated by UV-Vis, XRD, spectroscopy and gravimetric techniques. Treatments with aqueous extracts showed the highest concentration of total soluble polyphenols (TSP) 32.12- 21.23 mg EAG/g DW, and antioxidant capacity (AOX) for ABTS assay. The best treatment for TSP and AOX was T4: 2.5% Hibiscus w/w, aqueous extracts, decoction, extract-to-carrier ratio 1:1 (w/w), proportion to carriers (MD:GA) 80:20 (w/w), 10000 rpm, 150°C. Taguchi L8 model is a tool that allows the use of multiple variables with a low number of treatments that indicate the drying conditions that give the best parameters, focusing mainly on TSP and AOX, in addition, is a good alternative for the preservation and stability of the PC in Hibiscus.

In this paper were analyzed the effects of double reduction and annealing during rolling process on texture evolution in an ultrathin sheet of low carbon steel. Experimental samples were obtained from each process stage. EBSD technique and correlated tools as orientation density functions and pole figures were used to analyze the microstructural changes and the texture. Results show that {111} recrystallized grains were formed during process, reducing dramatically gamma-fibre texture intensity and generating an adequate finished product for deep die stamping.

In this study, the pristine MgO, MgO/CNT and Ni-MgO/CNT nanocomposites were processed by the impregnation and chemical vapour deposition methods and analyzed for hydrogen evolution (HER) via electrochemical water splitting process. Furthermore, effect of nickel on the deposited carbon was systematically elaborated in this study. The highly conductive carbon nanotubes (CNTs) deposited on the metal surface of the Ni-MgO nanocomposite heterostructure provides the robust stability and superior electrocatalytic activity. The optimized Ni-MgO/CNT nanocomposite exhibited hierarchical helical-shaped carbon nanotubes adorned on the surface of the Ni-MgO flakes, forming a hybrid metal-carbon network structure. The HER catalytic reaction was carried out in 1M alkaline KOH electrolyte, and the optimized Ni-MgO/CNT nanocomposite achieves the low 117 mV overpotential value (ɳ) at the 10 mA cm-2 and needs low 116 mV/dec Tafel value denoted Volmer-Heyrovsky pathway. Also, high electrochemical active surface area (ECSA) value of Ni-MgO/CNT nanocomposite acquires 515 cm2, which is favorable for the generation of abundant electro-active species and the prepared electrocatalyst durability was also performed by chronoamperometry test for prolonged duration of 20 h at 10 mA cm-2 and exhibits the good stability with 72% retention. Hence, obtained results demonstrated that the optimized Ni-MgO/CNT nanocomposite is highly active and cost-effective electrocatalyst towards hydrogen energy production.

In the present article, we study the possibilities of machine learning for estimation of seeing at the Maidanak Astronomical Observatory (38∘40′24′′N, 66∘53′47′′E) using only Era-5 re-analysis data. Seeing is usually associated with the integral of the turbulence strength Cn2(z) over the height z. Based on the seeing measurements accumulated over 13 years we created ensemble models of multi-layer neural networks under the machine learning framework, including training and validation. For the first time in the world, we have simulated optical turbulence (seeing variations) during night-time with deep neural networks trained on a 13-year database of astronomical seeing. A set of neural networks for simulations of night-time seeing variations have been obtained. For these neural networks the linear correlation coefficient ranges from 0.48 to 0.68. We show that modeled seeing with neural networks is well described through meteorological parameters, which include wind speed components, air temperature, humidity and turbulent surface stresses. One of the fundamental new results is that the structure of small-scale (optical) turbulence over the Maidanak Astronomical Observatory does not depend or depends negligibly on the vortex component of atmospheric flows.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

We aimed to assess whether play behavior can be used as a welfare indicator for farmed spotted pacas (Cuniculus paca) by examining its association with other positive welfare markers including affiliative behavior and low-amplitude vocalizations. We submitted six groups of spotted pacas (one male/two females per group) (N=18) to an ABA experimental design (A1/A2: without ball; B: with three boomer balls). Play behavior occurred only during phase B (mean=35.5s, SE=6.4). Spotted pacas spent more time in affiliative and exploratory behaviors, while they spent less time engaging in agonistic interactions during phase B than in both control phases (A1 and A2) (P<0.05). Moreover, spotted pacas emitted more low-amplitude bark vocalizations during phase B than during either control phase (P<0.05), which have previously been shown to indicate a positive affective state and low arousal level. Because the expression of play was associated with a decrease in aggression, an increase in affiliative behavior, and an increase in low-amplitude barking, indicating thus a positive state, we suggest that play behavior can be used as a non-invasive indicator of positive welfare in this species.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicted advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus autofluorescence (FAF), near-infrared reflectance (NIR), widefield imaging, optical coherence tomography (OCT), multicolor confocal scanning laser ophthalmoscopy (cSLO), and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. Multifocal electroretinogram (ERG) and microperimetry are methods for quantifying visual function to map disease progression. The evolving diverse imaging modalities optimize detection of pathology anatomy and measurement of visual function; they may also contribute to the understanding of the underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

Imaging-based biomarkers have developed as an effective tool in neurology, providing vital understandings of the structural, functional, and molecular changes associated with neurological disorders. Imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) have been widely employed to record disease-related alterations in the brain. These techniques provide a wide range of biomarkers, such as functional connectivity patterns, volumetric measurements, molecular imaging agents, and perfusion parameters, enabling the correct identification of neurological disorders. These biomarkers have proven useful in early diagnosis, disease progression tracking, therapy response prediction, and surgical planning. This review emphasizes the various obstacles and limitations that are associated with imaging-based biomarkers. Technical constraints, standardization obstacles, ethical concerns, regulatory challenges, and cost-effectiveness concerns all offer substantial barriers to wider use. It is vital to overcome these challenges if imaging biomarkers are to be successfully integrated into routine clinical practice. Imaging technology advancements like high-resolution imaging, multimodal imaging, and artificial intelligence-based analysis hold immense promise for imaging-based biomarkers in the future. While more study and standardization are needed, their ongoing development and integration into clinical practice have the potential to revolutionize the diagnosis, treatment, and management of neurological disorders, resulting in better patient care and outcomes.

Autoinflammatory disorders encompass a wide range of conditions with systemic and neuro-logical symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reac-tion. On the other hand, autoimmune diseases result from dysregulation of the adaptive im-mune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflam-matory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.

A new approach to preparing a series of Co/Sm2O3 catalysts for hydrogen production by dry re-forming of methane (DRM) is developed. The catalysts precursors are synthesized by a simple method, including evaporation of aqueous solutions of cobalt and samarium nitrates, followed by a short-term calcination of the resulting material. The as-prepared and spent catalysts are characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), temperature-programmed reduction (H2-TPR), and thermogravimetric analysis (TGA). It is shown that the content of cobalt in the synthesized materials affects their phase composition and carbonization resistance in the DRM reaction. It is demonstrated that preheating under N2 affords catalysts providing stable hydrogen and CO yields of 94-98 % for at least 50 h at 900°C. These yields are among the highest ones currently available for DRM catalysts derived from Co-Sm complex oxides. It is found that reduction in the amount of cobalt in the catalyst and its preheating to an operating temperature of 900°C in a nitrogen flow con-tribute to preventing catalyst carbonization and metal particles sintering.

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

The physiological characteristics of liquid digestate retrieved from various biogas plants based in northern Greece are presented. Preliminary photocatalysis experiments on inoculated liquid di-gestate sampled showed that disinfection is possible when pre-treated digestate with a combination of centrifuge-flocculation-μFiltration after 5.5 hours of 0.7g/L suspended TiO2 under UVA illumination for the experimental conditions is used. A novel design photocatalytic nanofiltration reactor was implemented for disinfection experiments on pre-treated liquid digestate, giving promising results. This work sets the basis for the efficient operation and engineering application of technology collaboration with photocatalysis as the final step for liquid digestate sanitation and reusable water recovery.

Ferroptosis is a unique variety of non-apoptotic cell death, driven by massive lipid oxidation in an iron-dependent manner. Since Ferroptosis was introduced as a concept in 2012, it was shown it's essential role in the pathogenesis in neurodegenerative diseases and an important role in therapy-resistant cancer cells. Thus, a detailed molecular understanding of both canonical and alternative ferroptosis pathways are required. There is a set of widely used chemical agents to modulate ferroptosis using different pathway targets: Erastin blocks cystine-glutamate antiporter, system xc-; ML210 directly inactivate GPX4; L-buthionine sulfoximine (BSO) inhibits γ-glutamylcysteine synthetase, an essential enzyme for glutathione synthesis de novo. Most studies were focused on lipidomic profiling of model systems undergoing death in a ferroptotic modality.

Abstract: Changes in sugar composition occur continuously in plants tissues, at different develop-mental stages. Tuber dormancy induction, stability, and breaking are very critical developmental transitions in yam crop production. Prolonged tuber dormancy after physiological maturity has constituted a great challenge in yam genetic improvement and productivity. In the present study, biochemical profiling of non-structural sugar in yam tuber during dormancy was performed to determine the role of non-structural sugar in yam tuber dormancy regulation. Two genotypes of white yam specie; one local genotype (Obiaoturugo) and (TDr1100873) were used for this study. Tubers were sampled at (42, 56, 87, 101, 115, and 143) days after physiological maturity (DAPM). Obiaoturugo exhibited a short dormant phenotype and sprouted at 101DAPM, whereas TDr1100873 exhibited a long-dormant phenotype, and sprouted at 143DAPM. Significant metabolic changes were observed in non-structural sugar parameters, dry matter, and moisture content in Obiaoturugo from 56DAPM, whereas, in TDr1100873 significant metabolic changes were observed from 101DAPM. It was observed that the onset of these metabolic changes occurred at a point when the tubers of both genotypes exhibited dry matter content of 60%, indicating that dry matter content of 60% might be a critical threshold for white yam tuber sprouting. Nonreducing sugars increased by 9-10-fold during sprouting in both genotypes which indicates its key role in tuber dormancy regulation in white yam. This result implies that some key sugar metabolites can be targeted for dormancy manipulation of yam crop.

Background: There is an increasing interest in the role of EEG in neurorehabilitation. We primarily aimed to identify the knowledge base through highly influential studies. Our secondary aims were to imprint the relevant thematic hotspots, research trends, and social networks within the scientific community. Methods: We performed an electronic search in Scopus looking for studies reporting on rehabilitation in patients with neurological disabilities. The most influential papers outlined the knowledge base, while a word co-occurrence analysis imprinted the research hotspots. Likewise, co-citation analyses highlighted collaboration networks between Universities, authors, and countries. The results were presented in summary tables, burst detection plots, and geospatial maps. Finally, a content review based on the top-20 most cited articles completed our study. Results: Our current bibliometric study was based on 874 records from 420 sources. There was a vivid research interest in EEG use for neurorehabilitation, with an annual growth rate as high as 14.3%. The most influential paper was the study titled "Brain-computer interfaces, a review" by Nicolas-Alfonso LF and Gomez-Gill J, with 997 citations, followed by "Brain-computer interfaces in neurological rehabilitation" by Daly J. and Wolpaw JR (708 citations). The USA, Italy, and Germany were among the most productive countries. The research hotspots shifted with time from the use of “functional magnetic imaging” to EEG-based “brain-machine interface”, “motor imagery”, and “deep learning”. Conclusions: EEG constitutes the most significant input in brain-computer interfaces (BCI) and can be successfully used in the neurorehabilitation of patients with stroke, amyotrophic lateral sclerosis, and traumatic brain and spinal injury. EEG-based BCI facilitates training, communication, and control of wheelchair and exoskeletons. However, research is limited to specific scientific groups from developed countries. Evidence is expected to change with the broader availability of BCI and improvement in EEG filtering algorithms.

Introduction:Few robust studies have analyzed association between cognitive tests and the marital status of Mild Cognitive Impairment (MCI) group with ADNI dataset. To test the hypothesis that Rey Auditory Verbal Learning test (RAVLT) cognition performance with marital status is associated with greater odds of MCI group than either RAVLT independently, we used TADPOLE data to evaluate cross-sectional associations between RAVLT performance in immediate response, learning, forgetting, and perception of forgetting with marital status and MCI. Methods: Subjects with MCI and Normal Cognition were included. Logistic regression models indicate associations between four RAVLT subgroups (low and high performance of immediate response, immediate response with learning, performance of immediate response with learning and forgetting, performance of immediate response with learning, forgetting and perception of forgetting) and MCI group. Models adjust for age, sex, race, marital status, ethnicity, education, APOE4 genotype, hippocampus, whole-brain, ventricles and ICV. Results: The sample (n=6560) had a mean age of 77 / 67 years, 44% were female, 58% in MCI group. Only all RAVLT subgroups test with age 61 to 70(OR 0.26, 95% CI 0.15-0.45), age 71 or older(OR 0.07, 95% CI,0.04-0.12), race:black/african american(OR 0.13, 95% CI 0.03-0.52)race:more than one(OR 0.05, 95% CI 0.01-0.24), marital status:never married(OR 0.2, 95% CI 0.12-0.34). Conclusion: Studies are needed to evaluate other cognitive test with missing data within TADPOLE dataset as modifiable risk factor for MCI.

During the COVID-19 pandemic, WIC increased the Cash Value Benefit (CVB) for fruits and vegetables by roughly $25/month/person. We sought to understand WIC participant perceptions of this change and barriers and facilitators to using the CVB. We conducted 10 virtual focus groups (5 rural, 5 urban/suburban) with WIC participants (n=55) in North Carolina in March 2022. Focus groups were recorded and transcribed. We open coded the content and used thematic analysis to uncover consistencies within and between sampled groups. Participants expressed favorable perceptions of the CVB increase and stated the pre-pandemic CVB amount was insufficient. Barriers to using the increased CVB were identifying WIC approved fruits and vegetables in stores and insufficient supply of fruits and vegetables. Barriers were more pronounced in rural groups. CVB use facilitators were existing household preferences for fruits and vegetables and the variety of products that can be purchased with the CVB relative to other components of the WIC food package. Participants felt the CVB increase allowed their families to eat a wider variety of fruits and vegetables. The CVB increase may improve fruit and vegetable intake, particularly if made permanent, but barriers to CVB and WIC benefit use may be limiting the potential impact.

Abstract Introduction: Urinary tract infections (UTIs) remain one of the most important problems of modern urology and medicine. Infections bring great discomfort and significantly reduce the quality of life. UTIs rank second after respiratory tract infections in outpatients. The most common pathogen of UTI are E.coli. The study of the etiology of UTI has great clinical and epidemiological importance in routine practice. Objective: To assess the etiological significance of pathogens in the occurrence of urinary tract infections in the Karaganda region of Kazakhstan. Methods: A total of 2378 patients presenting UTIs were enrolled and each provided a urine sample. The study was carried out in the Clinical Microbiology Laboratory MediTEC-NS between 2 January and 29 December 2018. Identification of isolated microorganisms was carried out on a WalkAway 96 Plus microbiological analyzer, Microscan model manufactured by Beckman Coulter (USA). Statistical Analysis was performed using the STATISTICA-6 package. Results: Out of 2378 patients a total of 1177 (49,5%) urine samples tested positive by culture test. From these samples, 1356 strains of microorganisms were isolated, of which 84.79% were monoculture and 21% were of a mixed culture. Gram-positive bacteria 690 (50, 88%), Gram-negative bacteria 630 (46, 46%), and Candida 36 (2.65%) were identified. Gram-negative rods were represented by Enterobacterales 557 (88.41%) and non-fermenting bacteria 73 (11.59%). In the Enterobacterales group included Escherichia coli 371 (66.61%) of which 108 (29,1%) ESBL strains. The next etiologically significant uropathogens were Klebsiella- 99 (17, 77%), Enterobacter-36 (6,46%) and Proteus-32 (8,09). K.pneumoniae prevailed in comparison with other Klebsiella spp. ESBL producing was 34 (57, 6%) out of 59 K.pneumoniae isolates. Gram-negative non-fermenting rod were represented by Acinetobacter spp-34 (46.57%) and Pseudomonas spp 31 (42.47%). Of 34 Acinetobacter spp. isolates 22 (64.7%) were identified as Acinetobacter lwoffii. Among the gram-positive pathogens of UTI, Staphylococcus spp prevailed - 411 (59.57%), followed by Enterococcus spp 197 (28.55%) and Streptococcus spp 81 (11.73%). Coagulase-negative staphylococci 381 (92,7%) isolates out of total 411 staphylococcal isolates. Staphylococcus epidermidis 245 (59,61%) and Staphylococcus haemolyticus 81 (21,17%) were the most frequent isolated coagulase-negative staphylococci. Of 411 staphylococcal isolates, 182 (44.28%) were MRS Conclusion: We found that UTIs among our study population were predominantly caused by ten opportunistic pathogens. The most common uropathogens with a frequency of 66.9% were E. coli- 30.53%, S. epidermidis -20.16%, and Enterococcus spp. -16.21%. Frequently isolated pathogens included Klebsiella, S. haemolyticus spp., and Streptococcus spp. which amounted to 21.98%. The distribution within the patient group was equable and ranged from 6,67% to 8,15%. Etiologically significant pathogens included Enterobacter spp., Proteus spp., Acinetobacter spp., Pseudomonas spp. These bacteria accounted for 11.11%. The distribution within the group was again equable and ranged within 2,55% to 2,96%.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Abstract: In the last five years, the urban development of Limassol City has rapidly increased in the sectors of industry, trade, real estate, and many others. This exponentially increased urban development introduces several concerns about the aggravation of the land subsidence in the Limassol coastal front. Fifty Copernicus Sentinel-1 data from 2017-2021 have been processed and analyzed using the Sentinel Application Platform (SNAP) and the Stanford Method for Persistent Scatters (StaMPS). A case study for the identification and analysis of the elements (PS) in pixels in a series of interferograms, and then, the quantity of the land displacements in the Line of Sight, in the Limassol coastal front, is presented in this research, with the subsidence rates up to about (-5 to 4 mm / year). For the validation of the detected deformation, accurate ground-based geodetic measurements along the coastal area were used. Concordantly, taking into account that there are a significant number of skyscrapers planned to be built, this study attempts a preliminary assessment of the impact these structures will pose on the coastal front of the area of Limassol.

: In our previous work we had developed an hxt-null Saccharomyces cerevisiae strain displaying high xylose reductase, xylitol dehydrogenase and xylulokinase activities that proved to be useful as a chassis strain to study new xylose transporters, as SsXUT1 from Scheffersomyces stipitis. Spathaspora passalidarum and Spathaspora arborariae have in their genomes genes with high sequence similarity (78-80%) to SsXUT1. To characterize these putative transporter genes (SpXUT1 and SaXUT1, respectively) they were expressed in the same chassis strain as SsXUT1. Surprisingly, the cloned genes could not restore the ability to grow in several monosaccharides tested, although the strains expressing the SsXUT1 and SpXUT1 permeases, after growth on maltose, showed the presence of 14C-glucose and 14C-xylose transport activity. An important feature of these permeases is that SsXUT1 lacks lysine residues in its N-terminal domain with high-confidence ubiquitinylation potential, and has only one at the C-terminal domain, while the SpXUT1 transporter had several of such residues at its C-terminal domain. When the SpXUT1 gene was cloned in a truncated version lacking such lysine residues, the permease allowed grow on glucose or xylose, and even promoted xylose fermentation by the hxt-null strain. In another approach, we deleted two arrestins known to be involved in sugar transporter ubiquitinylation and endocytosis (ROD1 and ROG3), but only the rog3Δ strain allowed modest growth on these sugars. Taken together, these results suggest that to allow efficient sugar transporter expression in S. cerevisiae the lysines involved in transporter endocytosis should be removed from the sequence of the permease.

We tested the hypothesis that obesity influences the pharmacodynamics of volatile general anesthetics (VGAs) by comparing effects of anesthetic exposure on mortality from traumatic brain injury (TBI) in lean and obese Drosophila melanogaster. We induced TBI with a High-Impact Trauma device. Starvation-selection over multiple generations resulted in an obese phenotype (SS flies). Fed flies served as lean controls (FC flies). Adult (1-7 day old) SS and FC flies were exposed to equianesthetic doses of isoflurane or sevoflurane either before or after TBI. The principal outcome was percent mortality 24 hours after injury, expressed as the Mortality Index at 24 hours (MI24). TBI resulted in lower MI24 in FC than in SS flies (21 (2.35) and 57.8 (2.14), respectively n= 12, p=0.0001). Preexposure to isoflurane or sevoflurane preconditioned FC flies to TBI reducing the risk of death to 0.53 [0.25 to 1.13] and 0.82 [0.43 to 1.58], respectively, but had no preconditioning effect in SS flies. Postexposure to isoflurane or sevoflurane increased the risk of death in SS flies. Only postexposure to isoflurane increased the risk in FC flies (1.39 [0.81 to 2.38]). Thus, obesity affects the pharmacodynamics of VGAs, thwarting the preconditioning effect of isoflurane and sevoflurane in TBI.

Study of fungal antibiotics in their competitive interactions with arthropods may lead to development novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained by various methods showed a wide range of biological activity, including entomotoxic properties. Analysis of their composition and bioactivity allowed to reveal several known mycotoxins and unidentified compounds that may be involved in entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with LT50 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited growth of G. mellonella larvae and caused mortality of Acheta domesticus imagines (LT50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact-intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing the 12 and 40% of mortality at a concentration of 1 mg/mL. TeA was cytotoxic to Sf9 cell line (IC50 25 µg/mL). Thus, model insect G. mellonella and cell line Sf9 could be used for a further toxicological characterization of TeA.

There are experimental evidences that chronic social defeat stress is accompanied by development of anxiety- and depression-like state as well as downregulation of serotonergic genes in the midbrain raphe nuclei of male mice. The study was aimed at investigating the effect of chronic lithium chloride (LiCl) administrations on anxiety behavior and the expression of serotonergic genes in the midbrain raphe nuclei of affected mice. The pronounced anxiety in male mice was caused by chronic social defeat stress in daily agonistic interactions. After 6 days of social stress, defeated mice were treated with saline or LiCl (100 mg/kg, i.p. two weeks) against the background of continuing agonistic interactions. The level of anxiety was assessed using behavioral tests. The effect of chronic treatment with LiCl on the expression of serotonergic genes in the midbrain rapher nuclei was also studied. Mild anxiolytic effects of LiCl were found on communication in the partition test. Anxiogenic-like effects assessed using the elevated plus-maze and social interaction tests were found. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei. The effects of chronic LiCl treatment depends on the method of treatment, psychoemotional state, and experimental context (tests).

The apicomplexan parasite Theileria haneyi is one of two known causative agents of equine theileriosis. It causes milder clinical disease than its more virulent counterpart, Theileria equi, in experimentally infected horses, and can superinfect T. equi-positive horses. The current EMA1-based competitive ELISA used in the U.S. to detect equine theileriosis detects T. equi but not T. haneyi, and the complexity of molecular assays precludes widespread use for epidemiologic studies. In order to facilitate urgently needed studies on the prevalence of T. haneyi, the goal of this study was to develop a sensitive and specific serologic assay for the diagnosis of T. haneyi based on the equi mero-zoite antigen 11 (ThEMA11). To achieve this objective, ThEMA11 was recombinantly expressed in eukaryotic cells and its antigenicity assessed using sera from T. haneyi-experimentally infected horses. Confirmation of sera reactiv-ity enabled design and optimization of an indirect ELISA. Specificity of the ELISA for T. haneyi was assessed using a cohort of sera from horses experimentally infected and confirmed PCR-positive for either T. equi or T. haneyi. Data from field samples further demonstrate that the ThEMA11 ELISA is capable of identifying T. haneyi antibodies in horses from multiple continents around the world.

The influence of a high inclusion level of Chlorella vulgaris, individually and supplemented with two carbohydrase mixtures, in finishing pig diets was assessed on zootechnical performance, carcass characteristics, pork quality traits and nutritional value of pork fat. Forty crossbred entire male pigs, sons of Large White × Landrace sows crossed with Pietrain boars, with an initial live weight of 59.1 ± 5.69 kg were used in this trial. Swines were randomly assigned to one of four dietary treatments (n=10): cereal and soybean meal-based diet (control), control diet with 5% C. vulgaris (CV), CV diet supplemented with 0.005% Rovabio® Excel AP (CV+R) and CV diet supplemented with 0.01% of a four-CAZyme mixture (CV+M). Animals were slaughtered, after the finishing period, with a BW of 101 ± 1.9 kg. Growth performance, carcass characteristics and meat quality traits were not influenced (p > 0.05) by the incorporation of C. vulgaris in the diets. However, the inclusion of the microalga in finishing pig diets increased some lipid-soluble antioxidant pigments and n-3 PUFA, and decreased the n-6:n-3 ratio of fatty acids, thus ameliorating the nutritional value of pork fat. Moreover, the supplementation of diets with the carbohydrase mixtures did not change (p > 0.05) neither animal performance nor meat quality traits, indicating their inefficacy in the increase of digestive utilization of C. vulgaris by pigs under these experimental conditions. It is concluded that the use of C. vulgaris in finishing pig diets, at this high incorporation level, improves the nutritional value of pork fat without compromising pig performance.

Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn prevent lifestyle diseases such as obesity. Epidemiological evidences suggest that an overdose of artificial sweeteners could result to adverse effects after consumption. Thus, our study aims to systematically explore the potential adverse effects of eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharin and sucralose on cardiac performances of zebrafish (Danio rerio) and Daphnia as model animals. Embryonic zebrafish and Daphnia were exposed to eight artificial sweeteners at 100 ppb concentrations and their cardiac performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output and heartbeat regularity) were measured and compared. Saccharin significantly increased the heart rate of zebrafish larvae while a significant decrease was observed in Daphnia. Significant increase was also noted in zebrafish heart rate variability after incubation in acesulfame K, dulcin, sodium cyclamate, and sucralose. However, a significant increase in Daphnia was only observed after incubation in dulcin. Based on Principal Component Analysis (PCA) and hierarchical clustering results, several artificial sweetener samples were species-specific to zebrafish and Daphnia. Our study demonstrates the potential adverse physiological effects of artificial sweeteners in cardiovascular systems of zebrafish larvae and Daphnia.

As a major infectious disease in chickens, Newcastle disease causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 dpi after infection at day21 with a lentogenic Newcastle disease virus in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV challenged and nonchallenged groups, 526 differentially expressed genes (DEGs) (FDR &lt; 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, IPA analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis and angiogenesis. Upregulation of Interferon Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK Signaling Antagonist 1 (SPRY1), a DEG in the current study is located in a significant QTL associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

There is a need for developmental screening that is easily administered in resource-poor settings. 1) We hypothesized that known risk factors would predict failed developmental screening on an adapted screening tool in East African children living in poverty. 2) The sample included 100 healthy Ugandan children aged 6-59 months. We adapted a parent-reported developmental screener based on the Child Development Review chart. The primary outcome was failure to meet age-appropriate milestones for any developmental domain. Venous blood was analyzed for lead, and caregivers completed a demographics questionnaire. We used multivariate logistic regression models to determine if elevated blood lead and stunting predicted failure on the screener, controlling for maternal education level, age in months past the lower bound of the child’s developmental age group, and absence of home electricity. 3) In the sample, 14% (n=14) of children failed one or more milestones on the screener. Lead levels or stunting did not predict failing the screener after controlling for covariates. 4) Though this tool was feasibly administered, it did not demonstrate preliminary construct validity and is not yet recommended for screening in high-risk populations. Future research should include a larger sample size and cognitive interviews to ensure it is contextually relevant.

The purpose of our work was the search for safe and effective biologically active substances of cardiotropic action among 1,3- thiazole derivatives. New derivatives of 1-[(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-yl]ethan-1-one and ethyl-(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-carboxylate were synthesized by the Hantzsch reaction. The structure of the compounds obtained was confirmed by ¹H NMR spectroscopy and by the elemental analysis. The pharmacological screening showed that the obtained substances possess cardiotropic activity. The cardiotropic properties of the new 1,3-thiazole derivatives were studied on the isolated rings of the thoracic aorta of laboratory rats. A prospective substance 1-[(2Z)-2-[(4-methoxyphenyl)imin]-4-methyl-3-(4-methylpiperazin-1-yl) -2,3-dihydro-1,3-thiazol-5-yl]ethan-1-one hydrochloride, which exhibits cardiotropic activity exceeding the activity of L-carnitine and meldonia has been revealed during pharmacological researches of the substances obtained.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

The mushroom industry generates large amounts of stems, a co-product with valuable sensory and health characteristics. This work aimed to study the influence of particle size (L — &gt;0.510 mm; LI — 0.510-0.315 mm; SI—0.315-0.180 mm; S — &lt;0.180 mm) and species in the characterization and antioxidant activity of flours from stems of Agaricus bisporus (ABSF) and Pleurotus ostreatus (POSF). ABSF was rich in protein (14 g/100 g), calcium (428.23-700.77 mg/100 g), and sorbitol (22.57-26.60 g/100 g), while POSF in β-glucans (36.62-40.34 g/100 g) and linoleic acid (20.57-39.86 g/100 g of lipid). Both species were flush in amino acids with umami flavor. The highest hydration properties and oil holding capacity were exhibited in the S size of both species. ABSF showed elevated values for emulsifying activity than POSF. ABSF-S recorded the heightened antioxidant capacity in vitro, in consonance with the total phenolic compounds (0.91 mg/g). However, this antioxidant assays in POSF presented a positive correlation with β-glucans content. According to these results, there could be several food applications for these co-products, such as emulsifier stabilizer, sweetener or fortifier in the development of functional food.

Mexico is a well-known seismically active country, which is primarily affected by several tectonic plate interactions along the southern Pacific coastline and by active structures in the Gulf of Baja California. In this paper we investigate this seismicity in the context of a non-extensive statistical approach based on Tsallis entropy. The analysis is performed using data from the corrected Mexican seismic catalogue provided by the National Seismic Service, spanning a period from January 2000 to October 2023. The Gutenberg-Richter law fitting to the earthquake sub-catalogues for all six regions studied indicates magnitudes of completeness between 3.30 and 3.76. All six regions display values of the entropic index in the range 1.52≲q≲1.61, which are lower than the previously estimated range 1.54≲q≲1.70 using catalogue data from 1988 to 2010. The cause of this discrepancy is certainly due to the use of modern recording devices, which are sensitive enough to detect a larger number of low-magnitude events compared to older instrumentation.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. The role of dysfunctional mitochondria in psychopathology is well-established, however, the association of these organelles with sleep physiology is novel. Indeed, reducing neuronal oxidative stress by importing mitochondria from astrocytes, may be the purpose of human slumber. This model may explain mitochondrial dysfunction during anesthesia as well as in the rare genetic disease, fatal familial insomnia. In this narrative review, we focus on the salience network of the brain, a common denominator for insomnia, neuropsychiatric and neurodegenerative disorders. We also discuss mitochondria-protecting strategies, including membrane lipid replacement, natural and synthetic phenazine and phenothiazine derivatives.

The extreme environmental issues and the resulting needs to save energy have turned the attention to electrification of energy applications. One of the key components involved in energy efficiency improvements is the appropriate conception and manufacturing of electric machines. This paper overviews the electromagnetic analysis governing the behavior of permanent magnets that enabled substantial efficiency gains in recent electric machine developments. Particular emphasis is given to model the properties and losses developed in permanent magnets in the emerging high speed applications. In addition, the investigation of properties and harmonic losses related to ferromagnetic materials constituting the machine magnetic circuits are equally analyzed and discussed. The experimental validation of the implemented methodologies and developed models with respect to the obtained precision is reported. The introduction of mixed numerical techniques based on the finite element method intended to appropriately represent the different physical phenomena encountered is outlined and discussed. Finally, fast and accurate simulation techniques including aggregated lumped parameter models considering harmonic losses associated with inverter supplies are commented.

Cardiovascular and cerebrovascular disease incidence has risen mainly due to poor control of preventable risk factors and still constitutes a significant financial and health burden worldwide. ChatGPT is an artificial intelligence language-based model developed by OpenAI. Due to the model’s unique cognitive capabilities beyond data processing and the production of high-quality text, there has been a surge of research interest concerning its role in the scientific community and contemporary clinical practice. To fully exploit ChatGPT's potential benefits and reduce its possi-ble misuse, extreme caution must be taken to ensure its implications ethically and equitably. In this article, we explore the language model's possible applications and limitations while empha-sizing its potential value for diagnosing, managing, and prognosis cardiovascular and cerebro-vascular disease.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL receptor deficient mice. CETP expression did not change lipid-stained lesion areas but decreased macrophage content (CD68), neutrophil accumulation (LY6G) and aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone marrow-derived cells reduces inflammatory features of atherosclerosis. These novel mechanistic observations may help explain the failure of CETP inhibitors to reduce atherosclerotic events in humans.

Rapid emergence of evasive SARS-CoV-2 variants is an on-going challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform on the sufficiency of the breadth of antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. Traditional analysis of neutralization titers against WT, Alpha, Beta, Delta, Omicron BA.1 and BA.4/BA.5 showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots and are known for their peculiar aromas and flavors. Axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation prompts searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) has been isolated and cultured, and its transcriptome has been analyzed under different in vitro culture conditions. The results show that the best T. borchii SP1 growth was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22ºC. The transcriptome analysis of this strain cultured in different media indicated that most of the gene transcription effort is due to a limited number of genes (20% of genes account for 80% of the transcription), that the transcription profile of the central metabolism genes was similar in the different conditions analyzed with a transcription signal detected for around 80% of the annotated genes. The gene expression profile suggests that T. borchii uses a fermentative rather than respiratory metabolism, even in aerobic conditions. Finally, there is a reduced expression of genes belonging to secondary metabolite clusters, whereas there is a significative transcription of those involved in producing volatile aromatic compounds.

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

Objective: The aim of the study was to characterize varieties of Moringa alfileria honey (unfloral and polyfloral) from Saudi Arabia based on antibacterial, antioxidant activities, physicochemical, melissopalynological analysis, total phenolic and flavonoid contents. Material and Methods: The fresh 376 honey samples (3 kg of each) were kindly provided by Alnahal aljwal Company, 2021 flowering season. The honey samples collected in sterile universal glass containers and kept at 2– 8°C until tested. Antibacterial, antioxidant activities and physiochemical analysis were done. Determination of sediment content, total grains, moisture content, water-soluble solids, acidity, electrical conductivity, total sugars content, inverted sugars, glucose (g/100 g), fructose (g/100 g), total glucose + fructose, fructose/ glucose ratio, sucrose (g/100 g), diastase enzyme activity and HMF were calculated. As well as total phenolic and flavonoid contents Results: Antibacterial activity and physiochemical analysis of honey samples w varied. All parameters studied were significantly different (P < 0.05) among all honey varieties. The results of the physiochemical analysis were compared with Saudi National Standard, Codex standard, as well as published data in the literature. Conclusion: It was obvious that the honey quality was varied based on the botanical origins

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

This research aimed to establish the relationship between carbon-nitrogen nutritional factors and copper sulfate on laccase activity (LA) by Pleurotus ostreatus. Culture media composition was tested to choose the nitrogen source. Yeast extract (YE) was selected as a better nitrogen source than ammonium sulfate. Then, the effect of glucose and YE concentrations on biomass production and LA as response variables was evaluated using central composite experimental designs with and without copper. The results showed that the best culture medium composition was glucose 45 gL-1 and YE 15 gL-1, simultaneously optimizing these two response variables. The fungal transcriptome was obtained in this medium with or without copper, and the differentially expressed genes were found. Main up-regulated transcripts included three laccase genes (lacc2, lacc6, and lacc10) regulated by copper, whereas the principal down-regulated transcripts included a copper transporter (ctr1) and a regulator of nitrogen metabolism (nmr1). These results suggest that Ctr1, which facilitates the entry of copper in the cell, is regulated by nutrient-sufficiency conditions. Once inside, copper induces transcription of laccase genes. This finding could explain why a 10 to 20-fold increase in LA occurs with copper compared to cultures without copper when using the optimal concentration of YE as nitrogen sources.

Introduction: There are unique technical and management challenges associated with living donor liver transplantation (LDLT) for Budd-Chiari Syndrome (BCS). The outcomes of LDLT for BCS in comparison to other indications remains unclear and warrants elucidation. Methods: Data of 24 BCS patients who underwent LDLT between January 2012 and June 2019 were analyzed. There were 20 adults and 4 children. The early and long-term outcomes of adult LDLT BCS patients were compared to a control group of LDLT patients for other indications and matched using propensity scoring methodology. Results: Primary BCS was observed in 22(91.7%) patients. Caval replacement was performed in 7(29.1%) patients. Early and late hepatic venous outflow tract (HVOT) complications were seen in 1(5.5%) and 3(16.7%) patients. Preoperative acute kidney injury was identified as a risk factor for mortality in the BCS cohort (p =0.013). On comparison, BCS recipients were younger with fewer comorbidities, more large volume ascites and higher rates of PVT. They also had longer cold ischemia time, increased blood loss and transfusion requirements, increased hospital stay, and higher late outflow complications. The 1-year and 3-year survivals were similar to non-BCS cohort (84.2% vs 94% and 70% vs 91.9%, respectively, log rank test p=0.09). Conclusion: LDLT is remains a good option for symptomatic BCS who have failed non-transplant interventions. The clinical and risk factor profile of BCS recipients is distinct from non-BCS recipients. By following an algorithmic management protocol, we show on propensity-score matched analysis that outcomes of LDLT for BCS are similar to non-BCS indications.

The prevalence of overweight/obesity in the adult population in the Philippines has doubled in the past 20 years. Zumba exercise has recently been implemented throughout the Philippines. However, there is scarce information on the effects of Zumba on obesity and Zumba participants’ characteristics in the Philippines. This study described the current practice of Zumba in the Philippines, along with the practitioners’ characteristics, and identified factors associated with Zumba participation. In this observational, cross-sectional study, a structured questionnaire was used to survey 10 Zumba locations in September 2019. Anthropometric measurements of participants were assessed. Respondents included 171 women (88.6%) and 22 men (11.4%), with a mean (±SD) age of 44.1 (± 8.9) years. All respondents answered that Zumba was enjoyable, and some answered “very enjoyable.” Determinants of frequent participation were as follows: being older than the mean age of participants, starting Zumba to enjoy dancing, starting Zumba not to lose weight, shopping mall location, and participation fee required. “To enjoy dance” being a motivation for Zumba practice was identified as a determinant of frequent participation, rather than “to lose weight.” The element of “enjoyable” may strongly influence continuation and frequent participation of Zumba exercise in the Philippines.

Psoriasis (PS) is an autoimmune skin disease mediated by immune cells that typically presents inflammatory erythematous plaques, and it is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature and reside in vascularized tissues. They can be activated by antigen provoking overexpression of pro-inflammatory cytokines and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophage to release IL-36, a powerful pro-inflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic pro-inflammatory diseases such as psoriasis. Suppressing IL-36 results in a noticeable improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra which binds on to IL-36 receptor ligand, but suppression can also occur by binding IL-38 to the IL-36R receptor. IL-38 specifically binds only to IL-36R and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs, a process that activates macrophages to secrete pro-inflammatory IL-36 inhibited by IL-38. In this article we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis and hold promise of an innovative therapeutic tool.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

Nisin is a 3.4 kDa antimicrobial peptide, produced by Lactococcus lactis (ATCC 11454). This bacteriocin can inhibit spores gemination and gram-positive bacteria development and has gained visibility in therapeutic use. The bacterial cellulose (CB) has been considered an ideal material and with high quality applied in food and medical-pharmaceutical inputs. Because of all this benefits, it is important to know the system proceeding of CB with nisin. Therefore, it was realize nisin release profile analysis of CBs was performed; analysis of the minimum inhibitory concentration (MIC) of nisin against Escherichia coli ATCC 25922, Pseudomonas aeuroginosa ATCC 9721 and Staphylococus aureus ATCC 10390; antimicrobial stability test, for 100 days at different temperatures of 4º, 25º and 37 ° C against microorganisms: S. aureus e L. sakei. The results show that nisin is released by the CB in 4 hours of contact with medium and the MIC of nisin is 78 µg/mL for S. aureus, doesn’t have gram-negative inhibition. It had stability until 100 days against L. sakei and 60 days for S. aureus. The system proved to be efficient and CB potentiated the antimicrobial action of nisin, acting as a selective barrier for other compounds present in the standard solution, serving as protection of the peptide at different temperatures. The CB loading system can be an ideal antimicrobial stability system for nisin.

Durability and performance of electrochemical energy converters such as fuel cells and electrolysers are not only dependent on the properties and the quality of the used materials. They strongly depend on operation conditions. Variations in external parameters, such as flow, pressure, temperature and, obviously, load can lead to significant local changes of current density, even local transients. The segmented cell technology was developed with the purpose to gain insight into local operation conditions in electrochemical cells, during operation. The operando measurement of the local current density and temperature distribution allows effective improvement of operation conditions, mitigation of potentially critical events and assessment of the performance of new materials. The segmented cell, which can replace a regular bipolar plate in the current state of the technology, can be used as monitoring tool and for targeted developments. This article gives an overview over the development and applications for proton exchange membrane fuel cell of this technology, such as water management or fault recognition. Recent advancements towards locally resolved monitoring of humidity and to current distributions in electrolysers are outlined.

The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

Hepcidin-25 was identified as the main iron regulator in the human body by binding to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as ATCUN (amino terminal Cu(II)- and Ni(II)- binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the formed complex of hepcidin-25 with copper could reveal insights into its biological role. The present work is mainly focused on the study of the metal-bound form of hepcidin-25, which could be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25, which was achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry MS/MS, high resolution mass spectrometry HRMS) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a 3D model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

This paper presents a demonstration of the feasibility of fabricating micro-cantilever harvesters with extended stress distribution and enhanced bandwidth by exploiting an M-shaped two-degrees-of-freedom design. The measured mechanical response of the fabricated device displays the predicted dual resonance peak behavior with the fundamental peak at the intended frequency. This design has the features of high energy conversion efficiency in a miniaturized environment where the available vibrational energy varies in frequency. It makes such a design suitable for future large volume production of integrated self powered sensors nodes for the Internet-of-Things.

The paper combines two new original concepts about eco-energetic systems. The first one is related to the M.E.N. (Mega-Eco-Nega-Watt) paradigm, which is based on three different but complementary ecological economic spaces: MEGAWATT, as needed energy, ECOWATT, as ecological energy, and NEGAWATT, as preserved energy, even the renewable energies and technologies, in the context of electrical energy production. The second concept presented in this paper is the eco-energetic efficiency, introduced in order to facilitate a correlation between the energetic efficiency of the system and a necessary, new defined ecological coefficient. The proposed formula for eco-energetic efficiency enables an interesting form of reporting to the different situations in which the input energy, output energy, lost energy and externalities, involved in an energetic process interact to produce energy in a specific energetic system, in connection with the circular economy model. Finally, is presented an original diagram of the energetic chains to produce electricity in a resilience regim, with high eco-energetic efficiency from originating in different primary energetic sources as external (gravitation & solar sources), fuels (classical & radioactive), internal sources and others. Even what kind of energetic sources are used to obtain electricity, as coals, gas, wood, hydropower, nuclear power, wind power, biomass, solar systems, and others, the entire process should be sustainable in what is the transdisciplinary integration of the different representative spheres as energy, socio-economy, ecology (environment), with the main core, sustainable education, inclueding the law and administrative aspects, as necessary fields of the knowledge based society/economy.

Nowadays, there has been a significant rise in the consumption of kefir, a functional beverage touted for its perceived health benefits. To offer a high-quality beverage to consumers, it is imper-ative to scrutinize and fine-tune the fermentation process. This study seeks to investigate the im-pact of fermentation time and the number of subcultures on the physicochemical, microbiological, and volatile composition, as well as the visual appearance of kefir beverages obtained from four consecutive 24- or 48-h batch subcultures. All fermented beverages exhibited low lactose, ethanol and acids levels, with counts of viable probiotic lactic acid bacteria and yeast exceeding 106 colony forming units/mL. The four kefir beverages from the 48-h batch subcultures notably showed the lowest total concentrations of volatile compounds likely due to overfermentation and overacidifi-cation of the beverages. This caused separation of the whey and curd, along with the formation of large gas bubbles, negatively affecting the visual appearance of the products. These findings em-phasize the importance of fine-tuning the fermentation process to ensure the production of high-quality kefir beverages that align with consumer preferences. The four beverages from the 24-h batch subcultures exhibited high microbiological and physicochemical stability during stor-age at 4 °C for 28 days.

The studied area (the Ionian Islands: Paxoi, Lefkas, Kefalonia and Zakynthos), is situated in the western ends of Ionian Basin (IB) in contact with the Apulian Platform (AP) and named as Apulian Platform Margins (APM). The proposed model is based on fieldwork, previously published data and balanced geologic cross-sections. Late Jurassic characterizes Ionian Basin to Early Eocene NNW–SSE extension followed by Middle Eocene to Middle Miocene compression (NNW–SSE directed). The space availability, the distance of Ionian Thrust from the Kefalonia strike-slip fault (KSSF) and the altitude between Apulian platform and Ionian basin that produced during extensional regime were the main factors for the produced structures due to inversion tectonic. In Zakynthos Island, the space availability (far from KFT), and the reactivation of normal bounding faults formed an open geometry anticline (Vrachionas anticline) and a foreland basin (Kalamaki thrust foreland basin). In Kefalonia Island, the space from FKT was limited and the tectonic inversion formed anticline geometries (Aenos Mountain), nappes (within the Aenos Mountain) and small foreland basins (Argostoli gulf), all within the margins (APM). In Lefkas Island, the lack of space, very close to KFT, lead to the movement of the Ionian basin over the margins, attempting to overthrust the Apulian platform. Because the obstacle between basin and platform was very large, the moving part of Ionian Basin strongly deformed producing nappes and anticlines in the external part of the Ionian basin, and a very narrow foreland basin (Ionian Thrust foreland basin).

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

: Controlling the distribution of water and wastewater between industrial processes is very vital in rationalizing water and preserving the environment. In this paper, a mathematical technique is proposed to optimize water-wastewater networks; a nonlinear program is introduced to minimize the consumption of freshwater, and consequently, the flowrate of the wastewater dis-charge will be also minimized. A general mathematical model, able to handle industrial plants containing up to eight sources and eight sinks, is developed using LINGO optimization software to facilitate dealing with complex case studies. The introduced model can handle single contam-inant networks as well as multiple contaminants cases. The optimal water network is synthe-sized through two steps; the first step is to introduce the case study data to the developed mathematical model. The second step considers using the optimal solution produced after run-ning the developed LINGO model as feed data for a pre-designed Excel sheet able to deal with these results and simultaneously draw the optimal water-wastewater network. The proposed mathematical model is applied to two case studies; The first case study includes actual data from four fertilizer plants located in Egypt; the water resources and requirements are simultaneously integrated to obtain a sensible cutting in both freshwater consumption (lowered by 52.2%) and wastewater discharge (zero wastewater discharge). The second case study is for a Brazilian pet-rochemical plant; the obtained results showed noticeable reductions in freshwater consumption for the second case study by 12.3 % while the reduction percentage of wastewater discharge is 4.5%.

Research on mental health and psychosocial support (MHPSS) interventions with displaced communities has increasingly focused on evaluating implementation, including identifying strategies to promote retention in services. This study examines the relationship between participant characteristics, study setting, and reasons for intervention noncompletion using data from the Entre Nosotras feasibility trial, a community-based MHPSS intervention targeting displaced and host community women in Ecuador and Panama that aimed to promote psychosocial wellbeing. Among 225 enrolled women, approximately half completed the intervention, with varying completion rates and reasons for nonattendance across study sites. Participants who were older, had migrated for family reasons, had spent more time in the study community, and were living in Panamá (vs. Ecuador) were more likely to complete the intervention. The findings suggest the need to adapt MHPSS interventions to consider the duration of access to the target population and explore different delivery modalities including the role of technology and cellular devices as reliable or unreliable source for engaging with participants. Engaging younger, newly arrived women is crucial, as they showed lower completion rates. Strategies such as consulting scheduling preferences, providing on-site childcare, and integrating MHPSS interventions with other programs could enhance intervention attendance.

Biomimetic materials are substances that replicate natural structures. There are several methods for producing such materials with highly developed surfaces from a wide range of polymers, but electrospinning is of particular interest due to its simplicity of implementation and the ability to modify the produced fibrous materials resembling structures found in living organisms. This study explores new biomimetic materials based on polyhydroxyalkanoates, specifically poly-3-hydroxybutyrate, modified with chlorophyll derivatives. The research investigates the impact of chlorophyll derivatives on the morphology, supramolecular structure, and key properties of nonwoven materials. The obtained results are of interest for the development of new biomimetic environmentally friendly materials for biomedicine with special properties.

Hispanics are disproportionately affected by low rates of physical activity and high rates of chronic diseases. Hispanics generally and Mexican Americans specifically are underrepresented in research on physical activity and its impact on mental well-being. Some community-based interventions have been effective in increasing physical activity among Hispanics. This study examined data from a sample of low-income Hispanic participants in free community exercise classes to characterize the association between self-reported frequency of exercise class attendance, intensity of physical activity, and participant well-being. As part of two cross-sectional samples recruited from a stratified random sample of community exercise classes, 302 participants completed a questionnaire consisting of a modified version of the Godin-Shephard Leisure-Time Exercise Questionnaire (LTEQ) and the Mental Health Continuum Short Form (MHC-SF). Adjusted binary logistic regression analyses indicated that those who achieve moderate and strenuous self-reported physical activity have 130% higher odds (p = 0.0422) of positive mental well-being after adjustment for age, attendance, and self-reported health. This study provides evidence that physical activity intensity and time are associated with flourishing mental health among Hispanics. The study provides insight into the planning and development of community-based physical activity programming tailored to low-income populations.

Background: This study aimed to investigate the effect of fascial manipulation (FM) of the deep cervical fascia (DCF) and sequential yoga poses (SYP) on pain and function in individuals with mechanical neck pain (MNP). Method: Following the predefined criteria, ninety-nine individuals with MNP were recruited, randomised and assigned to either the intervention group (IG) (n=51) or the control group (CG) (n=48). Individuals in the IG received FM (4 sessions in 4 weeks) along with the home-based SYP (4 weeks). The CG participants received the usual care (cervical mobilization and thoracic manipulation (4 sessions in 4 weeks) along with unsupervised therapeutic exercises (4 weeks). The participants underwent baseline and weekly follow-up measurements of pain using a numerical pain rating scale (NPRS) and elbow extension range of motion (EEROM) during upper limb neurodynamic test 1 (ULNT1). The baseline and the 4th session follow-up measurements of the Patient-specific Functional Scale (PSFS) and Fear-avoidance Behavior Questionnaire (FABQ) were also taken. Results: A repeated-measures ANOVA was performed. The mean differences between the IG and CG on NPRS 3rd and 4th sessions are -1.009 (p&lt; 0.05) and -1.701 (p&lt; 0.001), respectively; on EEROM in the 4th session is 20.120 (p&lt; 0.001); on FABQ during the follow-up is -5.036 (p&lt;0.001), showing a statistically significant difference, whereas on PSFS during follow-up is 0.263 (p=0.566), suggesting no significant differences in PSFS. Conclusion: FM and SYP can aid in reducing pain and fear avoidance behavior as well as improving the function and extensibility of the upper quarter region.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and is-chemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients so as to prevent and minimize the morbidity of HIBI. Further studies aimed at stand-ardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metastases-free survival; overall survival; toxicity.

Introduction: Previous studies have suggested that the tyrosine kinase receptor RET plays a sig-nificant role in the hematopoietic potential in mice and could also be used to expand cord-blood derived hematopoietic stem cells (HSCs). The role of RET in the human iPSC-derived hematopoi-esis has not been tested so far. Methods: To test the implication of RET on the hematopoietic potential of iPSCs, we activated its pathway with the lentiviral overexpression of RETWT or RETC634Y mutation in normal iPSCs. An iPSC derived from a patient harboring the RETC634Y mutation (iRETC634Y) and its CRISPR-corrected isogenic control iPSC (iRETCTRL) were also used. Hematopoietic potential was tested using 2D cul-tures and evaluated regarding the phenotype and the clonogenic potential of generated cells. Results: Hematopoietic differentiation from iPSCs with RET overexpression (WT or C634Y) led to a significant reduction in the number and in the clonogenic potential of HSCs (CD34+/CD38-/CD49f+) as compared to control iPSCs. Similarly, the hematopoietic potential of iRETC634Y was reduced as compared to iRETCTRL. Transcriptomic analyses revealed a specific ac-tivated expression profile for iRETC634Y compared to its control with evidence of overexpression of genes which are part of the MAPK network with negative hematopoietic regulator activities. Conclusion: RET activation in iPSCs is associated with an inhibitory activity in iPSC-derived hematopoiesis, potentially related with MAPK activation.

This study aimed to investigate the occurrence of the artificial sweetener aspartame (E951) in a wide range of foods and beverages sampled by food control authorities in Germany between 2000 and 2022. The dataset was obtained through the Consumer Information Act. The results showed that aspartame was present in a wide range of product groups tested, most commonly in powdered drink bases (84%) and flavored milk drinks (78%). In the solid food groups, the highest mean aspartame content was found in chewing gum (1543 mg/kg, n=241), followed by sports foods (1453 mg/kg, n=125), fiber supplements (1248 mg/kg, n=11), powdered drink bases (1068 mg/kg, n=162), and candies (437 mg/kg, n=339). Liquid products generally had the highest aspartame content in diet soft drinks (91 mg/l, n=2021), followed by regular soft drinks (59 mg/l, n= 574), flavored milk drinks (48 mg/kg, n=207), and mixed beer drinks (24 mg/l, n=40). These results suggest that aspartame is widely used in foods and beverages in Germany and that certain product groups contain higher concentrations of the sweetener than others. However, the levels of aspartame found were generally within the legal limits set by the European Union. These findings provide the first comprehensive overview of aspartame in the German food market and may be particularly useful in informing the forthcoming working groups of the WHO International Agency for Research on Cancer (IARC) and the WHO/FAO Joint Expert Committee on Food Additives (JECFA), which are in the process of evaluating the human health hazards and risks associated with the consumption of aspartame.

Over recent decades, therapeutic proteins have had widespread success in treating a myriad of diseases. Glycosylation, a near universal feature of this class of drugs, is a critical quality attribute that significantly influences the physical properties, safety profile and biological activity of therapeutic proteins. Optimizing protein glycosylation, therefore, offers an important avenue to developing more efficacious therapies. In this review, we discuss specific examples of how variations in glycan structure and glycoengineering impacts the stability, safety, and clinical efficacy of protein-based drugs that are already in the market as well as those that are still in preclinical development. We also highlight the impact of glycosylation on next generation biologics such as T cell-based cancer therapy and gene therapy.

Research with deuterium-depleted water (DDW) in the last two decades proved that deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted organic compounds (DDOC) alone and in combination with DDW on cancer growth in two in vivo mouse models. To produce DDOC, drinking water of laying hens was replaced with DDW (25 ppm) for 6 weeks, resulting in 60 ppm D level in dried egg yolk that was used as deuterium-depleted food additive. In one model, 4T1, a cell line with high metastatic capacity to the lung, was inoculated in the mice’s mammary pad. After three weeks of treatment with DDW and/or DDOC, the tumor volume in the lungs was smaller in all treated groups vs. controls with natural D level. Tumor growth and survival in mice transplanted with MCF-7 breast cancer cell line showed that the anticancer effect of DDW was enhanced by food containing the deuterium-depleted yolk. The study confirmed the importance of D/H ratio not only in consumed water but also in metabolic water produced by the mitochondria while oxidizing nutrient molecules. This is in line with the concept that initiation of cell growth requires the cells to generate a higher D/H ratio, but DDW, DDOC, or the naturally low-D lipids in a ketogenic diet, have significant effect on tumor growth by preventing the cells from raising D/H ratio to the threshold.