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Abstract Protein kinase C is a family of kinases that play important roles in carcinogenesis. Medicinal plants from Plectranthus spp. (Lamiaceae) are a well-known source of interesting abietanes, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy). This study aimed to extract and isolate Roy from P. grandidentatus Gürke, comparing two extraction methods (CO2 supercritical and ultrasound-assisted acetonic extraction), and design new royleanone derivatives for PKC modulation focusing on breast cancer therapy. The concentration of Roy in the extracts was determined by HPLC–DAD. The supercritical extraction method yielded 3.6% w/w, with the presence of 42.7 μg mg−1 of Roy (yield of 0.13%), while ultrasound-assisted acetonic extraction yielded 2.3% w/w, with the presence of 55.2 μg mg−1 of Roy (yield of 0.15%). The reactivity of Roy was investigated aiming at synthetizing new ester derivatives through standard benzoylation and esterification reactions. The benzoylated (Roy-12-Bz) and acetylated (Roy-12-Ac) derivatives in the C12 position were consistently prepared with overall good yields (33–86%). These results indicate the 12-OH position as the most reactive for esterification, affording derivatives under mild conditions. The reported di-benzoylated (RoyBz) and di-acetylated (RoyAc) derivatives were also synthesized after increasing the temperature (50 °C), reaction time, and using an excess of reagents. The cytotoxic potential of Roy and its derivatives was assessed against breast cancer cell lines, with RoyBz emerging as the most promising compound. Derivatization at position C-12 did not offer advantages over di-esterification at positions C-12 and C-6 or over the parent compound Roy and the presence of aromatic groups favored cytotoxicity. Evaluation of royleanones as PKC-α, βI, δ, ε, and ζ activators revealed DeRoy’s efficacy across all isoforms, while RoyPr showed promising activation of PKC-δ but not PKC-ζ, highlighting the influence of slight structural changes on isoform selectivity. Molecular docking analysis emphasized the importance of microenvironmental factors in isoform specificity, underscoring the complexity of PKC modulation and the need for further exploration.

IntroductionSome cyanobacteria can use far-red light (FRL) to drive oxygenic photosynthesis, a phenomenon known as Far-Red Light Photoacclimation (FaRLiP). It can expand photosynthetically active radiation beyond the visible light (VL) range. Therefore, it holds promise for biotechnological applications and may prove useful for the future human exploration of outer space. Typically, FaRLiP relies on a cluster of ~20 genes, encoding paralogs of the standard photosynthetic machinery. One of them, a highly divergent D1 gene known as chlF (or psbA4), is the synthase responsible for the formation of the FRL-absorbing chlorophyll f (Chl f) that is essential for FaRLiP. The minimum gene set required for this phenotype is unclear. The desert cyanobacterium Chroococcidiopsis sp. CCMEE 010 is unusual in being capable of FaRLiP with a reduced gene cluster (15 genes), and it lacks most of the genes encoding FR-Photosystem I.MethodsHere we investigated whether the reduced gene cluster of Chroococcidiopsis sp. CCMEE 010 is transcriptionally regulated by FRL and characterized the spectral changes that occur during the FaRLiP response of Chroococcidiopsis sp. CCMEE 010. In addition, the heterologous expression of the Chl f synthase from CCMEE 010 was attempted in three closely related desert strains of Chroococcidiopsis.ResultsAll 15 genes of the FaRLiP cluster were preferentially expressed under FRL, accompanied by a progressive red-shift of the photosynthetic absorption spectrum. The Chl f synthase from CCMEE 010 was successfully expressed in two desert strains of Chroococcidiopsis and transformants could be selected in both VL and FRL.DiscussionIn Chroococcidiopsis sp. CCME 010, all the far-red genes of the unusually reduced FaRLiP cluster, are transcriptionally regulated by FRL and two closely related desert strains heterologously expressing the chlF010 gene could grow in FRL. Since the transformation hosts had been reported to survive outer space conditions, such an achievement lays the foundation toward novel cyanobacteria-based technologies to support human space exploration.

Abstract Background and Aim Obesity has been a global public health issue due to the increasing mortality rate and prevalence among children. However, there are scarce studies on obesity prevalence in Hong Kong children. The study aims to identify the risk factors of obesity among primary and secondary school students by assessing the relationship between sociodemographic factors, health‐related behaviors, and social relationships. Methods Self‐administrated surveys were collected from 30 primary schools and 25 secondary schools participating in the “Quality Education Fund Thematic Network on Health Schools” project. Descriptive analysis was conducted to examine the proportions of different characteristics and to compare the disparity between primary and secondary school students with obesity. Results A total of 4884 responses were collected. A larger proportion of primary school students with obesity were male (adjusted odds ratio [aOR]: 2.55, 95% confidence interval [CI]: 1.77–3.67, p

Abstract Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo‐fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material‐ and pregnancy stage‐specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO2) and titanium dioxide (TiO2) NPs) and environmental NPs (diesel exhaust particles, DEPs). This includes a multitude of secreted inflammatory, vascular, and endocrine placental factors as well as extracellular vesicle (EV)‐associated proteins. Moreover, conditioned media (CM) from NP‐exposed explants induce pronounced anti‐angiogenic and anti‐vasculogenic effects, while early neurodevelopmental processes are only marginally affected. These findings underscore the potential of metal oxide NPs and DEPs for widespread interference with the placental secretome and identify vascular morphogenesis as a sensitive outcome for the indirect developmental toxicity of different NPs. Overall, this work has profound implications for the future safety assessment of NPs for industrial, commercial, or medical applications in pregnancy, which should consider placenta‐mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies.

Bradyrhizobium japonicum bacteria on the intensity of nodulation during nine phenophases (R1-R7) in relation to the isoflavone content in soybean seeds. Nine domestic soybean varieties were sown in three replicates, with Bradyrhizobium japonicum inoculated and non-inoculated seeds. The different morphological characteristics of nodules, the number and mass of nodules were studied during plants’ ontogenesis. The content of individual isoflavones in the sowing seed material was determined using high performance liquid chromatography mass spectrometry (HPLC-MS). The most abundant isoflavone was acetylgenistin in the variety Galeb (2741.4 μg/g), and the highest content of all isoflavones was recorded in the variety Gorštak (8117.7 μg/g). The variety Sava of the inoculated treatment exhibited the highest average values of the nodule mass (21.1 mg) and the highest number of nodules (23.3) in the phenophase, in which 10% of pods reached full length (R4). The average values of mass and number of nodules were calculated for the entire vegetation period, being higher in the inoculated treatment. There was no positive correlation between the content of isoflavones in seeds and the number and mass of nodules. The impact of quantity of isoflavone on nodulation intensity in soybeans was not significant,, which could be related to already saturated soil with nitrogen-fixing bacteria.

The study of migrant entrepreneurship in Russia is a relatively recent and complex social phenomenon. Its uniqueness stems from the surge in international migration, primarily from former regions of the Soviet Union, coinciding with significant socio-economic transformations, specifically the shift from the Soviet centrally planned economy to a market economy. This context partly explains the limited empirical research and the absence of a comprehensive theoretical foundation for such studies in Russian social science. Seeking to fill this gap, this article provides a brief overview of migrant entrepreneurship approaches, methods, empirical evidence, and findings. The research compares the data on migrants from Azerbaijan and Kyrgyzstan who started their businesses since the 1990s. The study includes 58 in-depth semi-structured interviews conducted between 2017 and 2019, supplemented by a questionnaire survey of Kyrgyz entrepreneurs (a sample of 200 persons), and an analysis of the Kyrgyz business platform, Tabarman, on social networks. The comprehensive analysis of the mutual influence of structural, group, and personal characteristics of migrants reveals ideal types and developmental stages in Kyrgyz and Azerbaijani migrant entrepreneurship in Russia across different post-Soviet periods. This article enhances our understanding of the complex dynamics of migrant entrepreneurship in the evolving socio-economic landscape of post-Soviet Russia.

Background/Objectives: The Trypanosoma cruzi infection promotes an intense inflammatory process that affects several tissues. The cholinergic system may exert a regulatory immune response and control the inflammatory process. This study aimed to evaluate the comparative effect of free and nanoencapsulated benznidazole in acute T. cruzi infection to assess hematological, biochemical, and oxidative status triggered by the cholinergic system. Methods: For this, fifty female Swiss mice were distributed in eight groups, i.e., uninfected and infected animals under four treatment protocols: untreated (control—CT); vehicle treatment (Eudragit L 100—EL-100); benznidazole treatment (BNZ); and nanoencapsulated benznidazole treatment (NBNZ). After eight treatment days, the animals were euthanized for sample collection. Results: The peak of parasitemia was at day 7 p.i., and the BNZ and NBNZ controlled and reduced the parasite rate but showed no efficacy in terms of total elimination of parasites analyzed by RT-PCR in both infected groups. The infection promotes significant anemia, leukopenia, and thrombocytopenia, which the BNZ improves. There was an increase in AChE activity during infection, leading to a pro-inflammatory response and an increase in M1 and M2 mACh receptors in the BNZ group, showing that the treatment interacted with the cholinergic pathway. In addition, a pro-oxidative response was characterized in the infection and mainly in the infected BNZ and NBNZ groups. The histopathological analysis showed significative splenomegaly and inflammatory infiltrate in the heart, liver, and spleen. Conclusions: The administration of the BNZ or NBNZ reverses hematological, hepatic, and renal alterations through cholinergic signaling and stimulates a pro-inflammatory response during acute T. cruzi infection.

The search for the microorganisms responsible for sulfide formation and corrosion of steel equipment in the oil fields of Tatarstan (Russia) resulted in the isolation of a new halotolerant strictly anaerobic sulfate-reducing bacterium, strain 5S69T. The cells were motile curved Gram-negative rods. Optimal growth was observed in the presence of 2.0–4.0% (w/v) NaCl, at pH 6.5, and at 23–28 °C under sulfate-reducing conditions. The isolate was capable of chemoorganotrophic growth with sulfate and other sulfoxides as electron acceptors, resulting in sulfide formation; and of pyruvate fermentation resulting in formation of H2 and acetate. The strain utilized lactate, pyruvate, ethanol, methanol, fumarate, and fructose, as well as H2/CO2/acetate for sulfate reduction. The genome size of the type strain 5S69T was 4.16 Mb with a G + C content of 63.0 mol%. On the basis of unique physiological properties and results of the 16S rRNA gene-based phylogenetic analysis, phylogenomic analysis of the 120 conserved single copy proteins and genomic indexes (ANI, AAI, and dDDH), assigning the type strain 5S69T ((VKM B-3653T = KCTC 25499T) to a new species within the genus Pseudodesulfovibrio, is suggested, with the proposed name Pseudodesulfovibrio methanolicus sp. nov. Genome analysis of the new isolate showed several genes involved in sulfate reduction and its sulfide-producing potential in oil fields with high saline formation water.

Acclimation through the hormesis effect increases the plasticity of organisms, which has been shown for many ectothermic animals, including fish. We investigated the effect of temperature acclimation in Baikal whitefish Coregonus baicalensis (Dybowski, 1874). Telomere length, telomerase activity, and the expression of genes, whose products are involved in the regulation of telomere length and defense against reactive oxygen species, were selected to assess the state of the larvae. Acclimation and acute temperature stress (+12 °C) had no effect on telomere length, but altered telomerase activity (acclimation decreased it; stress increased it) and the levels of genes expression. Under stress, the expression of superoxide dismutase genes was increased in acclimated larvae and that of glutathione peroxidases in non-acclimated larvae, which may indicate lower reactive oxygen species formation and slower antioxidant responses in acclimated fish. The expression of some telomere-related genes was reduced under temperature stress, but the expression of the tzap and smg genes, whose products improve the control of telomere length by preventing them from lengthening or shortening, was increased in acclimated individuals. The data obtained indicate a positive effect of acclimation on the state of the Baikal whitefish larvae by remodulation of their telomerase activity and the transcriptional profile.

Tea plant calli (Camellia sinensis L.) are characterized by the accumulation of various phenolic compounds (PC)—substances with high antioxidant activity. However, there is still no clarity on the response of tea cells to light exposure of varying intensity. The purpose of the research was to study tea callus cultures grown under the influence of primary exposure to different light intensities (50, 75, and 100 µmol·m−2·s−1). The cultures’ growth, morphology, content of malondialdehyde and photosynthetic pigments (chlorophyll a and b), accumulation of various PC, including phenylpropanoids and flavanols, and the composition of catechins were analyzed. Primary exposure to different light intensities led to the formation of chloroplasts in tea calli, which was more pronounced at 100 µmol·m−2·s−1. Significant similarity in the growth dynamics of cultures, accumulation of pigments, and content of malondialdehyde and various phenolics in tea calli grown at light intensities of 50 and 75 µmol·m−2·s−1 has been established, which is not typical for calli grown at 100 µmol·m−2·s−1. According to data collected using high-performance liquid chromatography, (+)-catechin, (−)-epicatechin, epigallocatechin, gallocatechin gallate, epicatechin gallate, and epigallocatechin gallate were the main components of the tea callus culture’s phenolic complex. Its content changed under the influence of primary exposure to light, reaching the greatest accumulation in the final stages of growth, and depended on the light intensity. The data obtained indicate changes in the morphophysiological and biochemical characteristics of tea callus cultures, including the accumulation of PC and their individual representatives under primary exposure to light exposure of varying intensity, which is most pronounced at its highest values (100 µmol·m−2·s−1).

IntroductionChildren are exposed to STEM ideas, including spatial and other mathematical concepts, in a variety of everyday contexts through interactions with their parents. There may be variations in the spatial language that boys and girls hear from their parents within different informal contexts. The present study investigated variations in the frequency and type of parental spatial talk that occurred in museum settings that varied by topic (physical science vs. life science) and exhibit scale (small-scale activity vs. large-scale activity).MethodThe sample consisted of 194 families with children between the ages of 3–6 years who visited museums in Northern California. Of the total sample, 50 families visited a large-scale physical science exhibit, 44 families visited a large-scale life science exhibit, 50 families visited a small-scale physical science exhibit, and 50 families visited a small-scale life science exhibit. Parent–child conversations that occurred during the duration of the museum visit were coded for parents’ spatial language.Results and discussionAnalyses revealed that parents in the large-scale life science exhibit used more spatial language than parents in the other exhibits. Additionally, parents used more “where” spatial language (spatial language that describes location and directionality) than “what” spatial language (spatial language that describes the look of something) across the exhibit contexts, but especially in the large-scale exhibits. Finally, boys heard more “where” spatial language than did girls across exhibit contexts, whereas there was no difference by gender for “what” spatial language exposure. Variations in the kinds of spatial language that parents use in different environments should be taken into account in developmental models of children’s spatial understanding. Future research is needed to more systematically explore how parents’ spatial language varies across children’s gender, exhibit topic, and exhibit scale.

Abstract This article focuses on the visual qualities of Alexander von Humboldt’s statistical tables in his Political Essay on the Kingdom of New Spain (1808–1811, 2nd ed. 1825–1827) with special attention to how such composites of numbers, alphabetical script, and semiotic elements relate to narrative writing. I argue that Humboldt’s tables/tableaus open up spaces inside his narrative that fragment the reading process, inviting new conversations, connections, and ideas. Resumen Este articulo entretiene con los atributos visuales de las abundantes tablas estadísticas incluyendo en el Essai politique sur le royaume de la Nouvelle Espagne (1808–1811, 2nd ed. 1825–1827) de Alexander de Humboldt, en especial con las relaciones entre las combinaciones de números, escritura y elementos semióticos (que Humboldt llama “tableaux”) y la propia narrativa. Obran estas relaciones una fragmentación del proceso de leer, abriendo dimensiones y espacios en que se podrían manifestar nuevas conexiones, conversaciones e ideas innovadoras. Zusammenfassung Dieser Artikel befasst sich mit den bildhaften Eigenschaften der vielen statistischen Tabellen in Alexander von Humboldts Essai politique sur le royaume de la Nouvelle Espagne (1808–1811, 2nd ed. 1820–1827), wobei meine besondere Aufmerksamkeit den Verhältnissen gilt, die diese aus Zahlen, alphabetischer Schrift und semiotischen Elementen zusammengesetzten Komposita (die Humboldt als Tableaux bezeichnet) mit der beschreibenden Erzählung selbst eingehen: In diesen Verhältnissen offenbaren sich nämlich Dimensionen oder Räumlichkeiten, die durch die visuelle Zerteilung des Textes stets weitere, neue Verbindungen, Gespräche und Ideen zu produzieren suchen

Abstract Background and Aims Unhealthy diets were found to be the main contributor to the overweight problem among adolescents. In this study, we aim to identify the factors causing unhealthy eating habits in adolescents. Methods School‐aged children and adolescents participated in this cross‐sectional observational study with additional school and parental consent. A self‐administered survey was conducted by 30 primary schools and 25 secondary schools. Participants were asked about the frequency of consuming unhealthy food and the types of unhealthy food consumed. A descriptive analysis was performed to demonstrate the proportions of characteristics. The prevalence of the outcome among participants of various factors was also analyzed using separate binary regression models. Results A total of 4884 responses were collected. Among primary school students (grade 4, mean age: 10.06), people who (1) were actively gaining weight (aOR: 1.651, 95% CI 1.006–2.708, p = 0.047), (2) went to bed after 11 p.m. (aOR: 1.652, 95% CI 1.065–2.563, p = 0.025), (3) had more than 2 h of gaming (aOR: 2.833, 95% CI 1.913–4.195, p

Abstract The future of physiology has been a recurrent concern for physiologists and Physiological Societies within post‐Bologna Europe and the European Higher Education Area (EHEA). Our paper provides an overview of Physiology teaching and research in Portugal, an EU member state and part of the EHEA. A descriptive study was designed to analyze data publicly available from the National Higher Education Directorate agency (DGES) from September to November 2022 to find all Portuguese syllabi containing at least one discipline related to human Physiology. A detailed database was established, including teaching staff, with a total of 365 courses/degrees and 764 Physiology disciplines. A bibliometric analysis of the identifiable lecturers' scientific production between 2017 and 2022 was made using Web of Science and PUBMED databases. Physiology is part of all health‐related professions. However, universities and technical colleges differ greatly in programs, staff backgrounds, and scientific profiles. Medical schools were found to provide the most complete formation. Noteworthy, the profession of Physiologist has practically no expression within the EHEA, compared with the USA‐UK realities. A better knowledge and understanding of these Physiology modalities in teaching and research within the EHEA will be instrumental to defining a stronger identity for European Physiology in the near future.

Abstract Striatal dysfunction has been implicated in the pathophysiology of schizophrenia, a disorder characterized by positive symptoms such as hallucinations and delusions. Haloperidol is a typical antipsychotic medication used in the treatment of schizophrenia that is known to antagonize dopamine D2 receptors, which are abundantly expressed in the striatum. However, haloperidol’s delayed therapeutic effect also suggests a mechanism of action that may go beyond the acute blocking of D2 receptors. Here, we performed proteomic analysis of striatum brain tissue and found more than 400 proteins significantly altered after 30 days of chronic haloperidol treatment in mice, namely proteins involved in glutamatergic and GABAergic synaptic transmission. Cell-type specific electrophysiological recordings further revealed that haloperidol not only reduces the excitability of striatal medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) but also affects D1-MSNs by increasing the ratio of inhibitory/excitatory synaptic transmission (I/E ratio) specifically onto D1-MSNs but not D2-MSNs. Therefore, we propose the slow remodeling of D1-MSNs as a mechanism mediating the delayed therapeutic effect of haloperidol over striatum circuits. Understanding how haloperidol exactly contributes to treating schizophrenia symptoms may help to improve therapeutic outcomes and elucidate the molecular underpinnings of this disorder.

Introduction: Interferon I (IFN I) signaling hyperactivation is considered one of the most important pathogenetic mechanisms in systemic lupus erythematosus (SLE). Early manifestation and more severe SLE courses in children suggest a stronger genetic influence in childhood-onset SLE (cSLE). Aim: To evaluate IFN-I score and SLE-associated genetic variants in cSLE. Material and Methods: 80 patients with cSLE were included in the study. IFN I-score was assessed by real-time PCR quantitation of 5 IFN I-regulated transcripts (IFI44L, IFI44, IFIT3, LY6E, MXA1) in 60 patients. Clinical exome sequencing (CES) was performed in 51 patients. Whole-exome sequencing was performed in 32 patients with negative results of CES. Results: 46/60 patients (77%) had elevated IFN-I scores. Leucopenia and skin involvement were associated with over-expression of IFI44 and IFI44L, while hypocomplementemia—with hyperactivation of IFIT3, LY6E, and MX1. No correlation of IFN-I score with disease activity was found. At least one rare genetic variant, potentially associated with SLE, was found in 29 (56.9%) patients. The frequency of any SLE-genetic variants in patients with increased IFN scores was 84%, in patients with normal IFN scores—33%, and in the group whose IFN score was not assessed was 65% (p = 0.040). The majority of genetic variants (74%) are functionally related to nucleic acid sensing and IFN-signaling. The highest frequency of genetic variants was observed in Sakha patients (9/14; 64.3%); three and two unrelated patients had identical variants in PTPN22 and TREX1 genes, respectively. Conclusions: More than half of patients with childhood-onset SLE have rare variants in SLE-associated genes. The IFN-I score could be considered a tool for the selection of patients for further genetic assessment in whom monogenic lupus is suspected.

Abstract Background To improve transmural palliative care for older adults acutely admitted to hospital, the PalliSupport intervention, comprising an educational programme and transmural palliative care pathway, was developed. This care pathway involves timely identification of palliative care needs, advance care planning, multidisciplinary team meetings, warm handover, and follow-up home visits. With this study, we evaluate changes in patient-related outcomes and transmural collaboration after implementation of the care pathway. Methods We conducted a before-after study, in which we compared 1) unplanned hospital admission and death at place of preference and 2) transmural collaboration before implementation, up to six months, and six to 18 months after implementation. Data from palliative care team consultations were collected between February 2017 and February 2020 in a teaching hospital in the Netherlands. Results The palliative care team held 711 first-time consultations. The number of consultation, as well as the number of consultations for patients with non-malignant diseases, and consultations for advance care planning increased after implementation. The implementation of the pathway had no statistically significant effect on unplanned hospitalization but associated positively with death at place of preference more than six months after implementation (during/shortly after adjusted OR: 2.12; 95% CI: 0.84–5.35; p-value: 0.11, long term after adjusted OR: 3.14; 95% CI: 1.49–6.62; p-value: 0.003). Effects on transmural collaboration showed that there were more warm handovers during/shortly after implementation, but not on long term. Primary care professionals attended multidisciplinary team meetings more often during and shortly after implementation, but did not more than six months after implementation. Conclusions The pathway did not affect unplanned hospital admissions, but more patients died at their place of preference after implementation. Implementation of the pathway increased attention to- and awareness for in-hospital palliative care, but did not improve transmural collaboration on long-term. For some patients, the hospital admissions might helped in facilitating death at place of preference.

Aims: Hyaline cartilage has a low capacity for regeneration. Untreated osteochondral lesions of the femoral head can lead to progressive and symptomatic osteoarthritis of the hip. The purpose of this study is to analyze the clinical and radiological long-term outcome of patients treated with osteochondral autograft transfer. To our knowledge, this study represents a series of osteochondral autograft transfer of the hip with the longest follow-up. Methods: We retrospectively evaluated 11 hips in 11 patients who underwent osteochondral autograft transfer in our institution between 1996 and 2012. The mean age at the time of surgery was 28.6 years (8 to 45). Outcome measurement included standardized scores and conventional radiographs. Kaplan-Meier survival curve was used to determine the failure of the procedures, with conversion to total hip arthroplasty (THA) defined as the endpoint. Results: The mean follow-up of patients treated with osteochondral autograft transfer was 18.5 years (9.3 to 24.7). Six patients developed osteoarthritis and had a THA at a mean of 10.3 years (1.1 to 17.3). The cumulative survivorship of the native hips was 91% (95% confidence interval (CI) 74 to 100) at five years, 62% (95% CI 33 to 92) at ten years, and 37% (95% CI 6 to 70) at 20 years. Conclusion: This is the first study analyzing the long-term results of osteochondral autograft transfer of the femoral head. Although most patients underwent conversion to THA in the long term, over half of them survived more than ten years. Osteochondral autograft transfer could be a time-saving procedure for young patients with devastating hip conditions who have virtually no other surgical options. A larger series or a similar matched cohort would be necessary to confirm these results which, in view of the heterogeneity of our series, seems difficult to achieve. Cite this article: Bone Jt Open 2023;4(7):523–531.

For agricultural production is used almost 40% of the global land from where it dominates conventional agriculture which uses large amounts of inputs in the form of fertilizers and pesticides leading to the contamination of soil, water resources, air pollution and land erosion, affects biodiversity and extinction of many plants and animals. On the other hand, the world's population is constantly growing and currently numbers more than 8 billion people and it is estimated that food production will have to double by 2050. In order to meet the future needs of the population for food raw materials, food production must significantly increase, and at the same time, the impact of agriculture on the environment and natural resources must be drastically reduced. Sustainable agriculture is emerging as one of the solutions. This way of agricultural practice refers to the management and preservation of natural resources through organizational and technological changes in modern agricultural production in order to satisfy human needs and preserve the environment. One of the most important natural resources on which the entire agricultural production relies is land. In intensively cultivated lands, there is a noticeable trend of intense degradation, which represents a major problem facing humanity. The paper reviews the decrease in soil fertility based on the samples collected during the five-year monitoring, as well as a proposal for measures to increase fertility and future preservation of this environmental resource.

Abstract Background Health literacy is essential in the promotion of healthy lifestyle habits and chronic disease prevention. Objective To assess the health literacy level among Hong Kong adolescents; to evaluate the association between access of an online health information platform (GoSmart Channel) and health literacy level; and to examine the association between health literacy level and various unhealthy behaviours. Design This study recruited students from 10 local secondary schools in Hong Kong to assess the health literacy level among adolescents. Settings and Participants Participants were required to complete a self‐administered questionnaire on health behaviours and health literacy using the Health Literacy Measure for Adolescents (HELMA). Main Outcome Measure Data were analysed using descriptive statistics and multivariate regression modelling. Results A total of 777 responses were collected. Overall, most (74.4%) of the adolescents in Hong Kong have limited health literacy (HELMA score

IntroductionThe inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed.MethodsIn this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues.ResultsWe demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation.DiscussionOverall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.

INTRODUCCIÓN: las gastroenteritis agudas (GEA) constituyen un grave y ocupante problema de Salud Pública. OBJETIVO: resultó de interés buscar bacterias (Salmonella spp. y Shigella spp.) virus (Rotavirus y Adenovirus) y parásitos en heces de niños con diarrea en un Hospital de la provincia de Córdoba, Argentina; para trazar un perfil etiológico en nuestra región. MATERIALES Y MÉTODO: se analizaron 137 muestras de heces de pacientes infanto-juveniles ambulatorios durante un año. RESULTADOS: 31 de las 137 muestras analizadas arrojaron resultados positivos (22,62%; n=137). De los casos positivos (n=31), 61,29% (19; n=31) correspondieron a aislamientos de los géneros Salmonella y Shigella, 9,67% (3; n=31) a diagnóstico de Rotavirus y 22,58% (7; n=31) a diagnóstico de parásitos intestinales. Dos de las muestras clínicas positivas presentaron coinfección (6,45 %); giardiosis y shigelosis y giardiosis y Rotavirus, respectivamente 25,80% de las bacterias estudiadas se presentaron en niños de 3 y 4 años de edad; 9,67% de las parasitosis, en niños de 6 y 7 años de edad y 6,45% Rotavirus, en niños de 1 y 2 años de edad. No hubo diferencias significativas en la distribución por sexo. DISCUSIÓN Y CONCLUSIONES: la vigilancia de las diarreas basada en los diagnósticos microbiológico y parasitológico provee información relevante que complementa el seguimiento clínico y epidemiológico creando un mapeo de la circulación de los agentes etiológicos en una determinada región.

Abstract Background Older patients are vulnerable to experiencing drug related problems (DRPs), which may result in emergency department (ED) visits. However, it is not standard practice to conduct medications reviews during ED visit. The aim of this study was to assess the number of DRPs in older patients living with frailty at the ED, identified through pharmacist-led medication reviews within a geriatric care team, and to determine the acceptance rate of pharmacists’ recommendations among hospital physicians and general practitioners or elderly care specialists. Methods A retrospective observational study was performed in patients ≥ 70 years living with frailty at the ED at Tergooi Medical Center. Pharmacist-led medication reviews were conducted to identify and classify DRPs as part of a larger geriatric assessment. The acceptance rate of given recommendations was determined during follow-up. Results A total of 356 ED visits were included. The mean (standard deviation, SD) age of patients was 83 (6.8) years. About 76% of patients had at least one DRP. In total, 548 DRPs were identified with a mean of 1.5 DRP (SD 1.3) per patient. The acceptance rate of medication recommendations in admitted patients was 55%, and 32% among general practitioners/elderly care specialists in discharged patients. Conclusions Pharmacist-led medication reviews as part of a geriatric care team identified DRPs in 76% of older patients living with frailty at the ED. The acceptance rate was substantially higher in admitted patients compared to discharged patients.

Abstract Background Timely access to essential obstetric and gynecologic healthcare is an effective method for improving maternal and neonatal outcomes; however, the COVID-19 pandemic impacted pregnancy care globally. In this global scoping review, we select and investigate peer-reviewed empirical studies related to mHealth and telehealth implemented during the pandemic to support pregnancy care and to improve birth outcomes. Methods We searched MEDLINE and PubMed, Scopus, CINAHL and Web of Science for this Review because they include peer-reviewed literature in the disciplines of behavioral sciences, medicine, clinical sciences, health-care systems, and psychology. Because our investigative searches reviewed that there is considerable ‘grey literature’ in this area; we did not restrict our review to any study design, methods, or place of publication. In this Review, peer-reviewed preprints were comparable to published peer-reviewed articles, with relevant articles screened accordingly. Results The search identified 1851 peer reviewed articles, and after removal of duplicates, using inclusion and exclusion criteria, only 22 studies were eligible for inclusion in the review published from January 2020 to May 2022. mHealth interventions accounted for 72.7% (16 of 22 studies) and only 27.3% (6 of 22 studies) were telehealth studies. There were only 3 example studies that integrated digital technologies into healthcare systems and only 3 studies that developed and evaluated the feasibility of mobile apps. Experimental studies accounted 68.8% of mHealth studies and only 33.3% studies of telehealth studies. Key functionalities of the pregnancy apps and telehealth platforms focused on mental and physical wellness, health promotion, patient tracking, health education, and parenting support. Implemented interventions ranged from breastfeeding and selfcare to behavioral health. Facilitators of uptake included perceived benefits, user satisfaction and convenience. Mobile apps and short messaging services were the primary technologies employed in the implemented mHealth interventions. Conclusion Although our Review emphasizes a lack of studies on mHealth interventions and data from pregnant women during the COVID-19 crisis, the review shows that implementation of digital health interventions during emergencies are inevitable given their potential for supporting pregnancy care. There is also a need for more randomized clinical trials and longitudinal studies to better understand the effectiveness and feasibility of implementing such interventions during disease outbreaks and emergencies.

Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) are classified as high-risk infections that can lead to death, particularly among older individuals. Nowadays, plant nanoparticles such as glycyrrhizic acid are recognized as efficient bactericides against a wide range of bacterial strains. Recently, scientists have shown interest in plant extract nanoparticles, derived from natural sources, which can be synthesized into nanomaterials. Interestingly, glycyrrhizic acid is rich in antioxidants as well as antibacterial agents, and it exhibits no adverse effects on normal cells. In this study, glycyrrhizic acid nanoparticles (GA-NPs) were synthesized using the hydrothermal method and characterized through physicochemical techniques such as UV–visible spectrometry, DLS, zeta potential, and TEM. The antimicrobial activity of GA-NPs was investigated through various methods, including MIC assays, anti-biofilm activity assays, ATPase activity assays, and kill-time assays. The expression levels of mecA, mecR1, blaR1, and blaZ genes were measured by quantitative RT-qPCR. Additionally, the presence of the penicillin-binding protein 2a (PBP2a) protein of S. aureus and MRSA was evaluated by a Western blot assay. The results emphasized the fabrication of GA nanoparticles in spherical shapes with a diameter in the range of 40–50 nm. The data show that GA nanoparticles exhibit great bactericidal effectiveness against S. aureus and MRSA. The treatment with GA-NPs remarkably reduces the expression levels of the mecA, mecR1, blaR1, and blaZ genes. PBP2a expression in MRSA was significantly reduced after treatment with GA-NPs. Overall, this study demonstrates that glycyrrhizic acid nanoparticles have potent antibacterial activity, particularly against MRSA. This research elucidates the inhibition mechanism of glycyrrhizic acid, which involves the suppressing of PBP2a expression. This work emphasizes the importance of utilizing plant nanoparticles as effective antimicrobial agents against a broad spectrum of bacteria.

The diterpene 7α-acetoxy-6β-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6β-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.

The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand–protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819–0.879). Strategic modifications altered HOMO–LUMO gaps (3.39–3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.

The current study investigates the venom-delivery system of green and red morphotypes of the sea anemone Actinia equina to disclose its potential as a source of bioactive compounds. We compared the two morphotypes using electron and optical microscopy, proteomics, and toxicity assessment on zebrafish embryos. Specialized venom-injecting cells (nematocysts) are equally distributed and found in the tentacles of both varieties. Proteomics revealed proteins of interest in both red and green Actinia, yielding the three most abundant Gene Ontology (GO) terms related to the biological processes “proteolysis”, “hemolysis in another organism” and “lipid catabolic process”. Neurotoxins and cytolytic toxins similar to known cnidarian toxins like PsTX-60A and AvTX-60A, for instance, were identified in both types. Extracts from green and red anemones were toxic to zebrafish embryos, with green anemone venom appearing to be more potent. The findings highlight the presence of proteinaceous toxins in A. equina and the potential for different varieties to possess distinct bioactive compounds. Notably, pore-forming toxins are suggested for molecular probes and immunotoxins, making them valuable assets for potential biotechnological and biomedical purposes.

Resistive metal/β-Ga2O3/metal structures with different interelectrode distances and electrode topologies were investigated. The oxide films were deposited by radio-frequency magnetron sputtering of a Ga2O3 (99.999%) target onto an unheated sapphire c-plane substrate (0001) in an Ar/O2 gas mixture. The films are sensitive to ultraviolet radiation with wavelength λ = 254. Structures with interdigital electrode topology have pronounced persistent conductivity. It is shown that the magnitude of responsivity, response time τr, and recovery time τd are determined by the concentration of free holes p involved in recombination processes. For the first time, it is proposed to consider hole trapping both by surface states Nts at the metal/Ga2O3 interface and by traps in the bulk of the film.

Previously, we found for the first time the participation of osmolytes in adaptation to acidic conditions in three acidophilic fungi. Because trehalose can protect membranes, we hypothesized a relationship between osmolyte and membrane systems in adaptation to stressors. In the mycelium of Phlebiopsis gigantea, the level of osmolytes reaches 8% of the dry mass, while trehalose and arabitol make up 60% and 33% of the sum, respectively. Cold shock does not change the composition of osmolytes, heat shock causes a twofold increase in the trehalose level, and osmotic shock leads to a marked increase in the amount of trehalose and arabitol. Predominance of phospholipids (89% of the sum) and low proportions of sterols and sphingolipids are characteristic features of the membrane lipids’ composition. Phosphatidic acids, along with phosphatidylethanolamines and phosphatidylcholines, are the main membrane lipids. The composition of the membrane lipids remains constant under all shocks. The predominance of linoleic (75% of the sum) and palmitic (20%) acids in phospholipids results in a high degree of unsaturation (1.5). Minor fluctuations in the fatty acid composition are observed under all shocks. The results demonstrate that maintaining or increasing the trehalose level provides stability in the membrane lipid composition during adaptation.

The mechanism of methylmannose polysaccharide (MMP) biogenesis in nontuberculous mycobacteria (NTM) is characterized, which involves an MMP-specific hydrolase (MmpH) and a rare mannosyltransferase (ManT). MmpH and ManT structures are presented.

Purpose. The purpose of the study is to determine the place, meaning, perspectives of the computer game simulator “The Sims” in the cultural space of youth, supplemented by a new digital environment, and to establish the reasons for its 20-year success. Methodology. The main theoretical and methodological approaches to the review of a computer game are systemic and complex. The specifics of the study revealed the need for a cause-and-effect analysis of the studied phenomenon. Results. The sociocultural aspect of young people involvement in the computer game “The Sims” is primary. The esthetic aspect (graphics, technical characteristics, which have been getting better and worse over for 20 years) is secondary. Namely the experience of attempt “life situations”, building own world, relationships, yourself attracts young players. Gamers see the game as a unique philosophy and values, that they share with the creators of the game, which is a prerequisite for the emergence of a digital cultural community based on a particular game. Given the wide range of players and interest in computer games, it is important to study them in a cultural context, since psychological and other characteristics go by the wayside (a variety of people play computer games, which is not associated with any personal characteristics, for example, introversion, self-doubt). Practical implications. The results of the study can be applied in philosophy, cultural studies and pedagogy.

Hemotropic Mycoplasma spp. (hemoplasmas) are uncultivable bacteria that infect mammals, including humans. We detected a potentially novel hemoplasma species in blood samples from wild river dolphins in the Amazon River Basin, Brazil. Further investigation could determine pathogenicity and zoonotic potential of the detected hemoplasma.

Abstract The main male hormone, testosterone is obtained from cheap and readily available phytosterol using the strains of Mycolicibacterium neoaurum VKM Ac-1815D, or Ac-1816D. During the first “oxidative” stage, phytosterol (5–10 g/L) was aerobically converted by Ac-1815D, or Ac-1816D to form 17-ketoandrostanes: androstenedione, or androstadienedione, respectively. At the same bioreactor, the 17-ketoandrostanes were further transformed to testosterone due to the presence of 17β-hydroxysteroid dehydrogenase activity in the strains (“reductive” mode). The conditions favorable for “oxidative” and “reductive” stages have been revealed to increase the final testosterone yield. Glucose supplement and microaerophilic conditions during the “reductive” mode ensured increased testosterone production by mycolicibacteria cells. Both strains effectively produced testosterone from phytosterol, but highest ever reported testosterone yield was achieved using M. neoaurum VKM Ac-1815D: 4.59 g/l testosterone was reached from 10 g/l phytosterol thus corresponding to the molar yield of over 66%. The results contribute to the knowledge on phytosterol bioconversion by mycolicibacteria, and are of significance for one-pot testosterone bioproduction from phytosterol bypassing the intermediate isolation of the 17-ketoandrostanes. Graphical Abstract

Discovering disease genes on the X chromosome can be particularly challenging. Here, the authors use features of known disease genes and machine learning to predict genes that remain to be associated with disorders on this chromosome.

Here the authors characterize structural variations (SVs) in a cohort of individuals with complex genomic rearrangements, identifying breakpoints by employing short- and long-read genome sequencing and investigate their impact on gene expression and the three-dimensional chromatin architecture. They find breakpoints are enriched in inactive regions and can result in chromatin domain fusions.

AimsAvascular femoral head necrosis in the context of gymnastics is a rare but serious complication, appearing similar to Perthes’ disease but occurring later during adolescence. Based on 3D CT animations, we propose repetitive impact between the main supplying vessels on the posterolateral femoral neck and the posterior acetabular wall in hyperextension and external rotation as a possible cause of direct vascular damage, and subsequent femoral head necrosis in three adolescent female gymnasts we are reporting on.MethodsOutcome of hip-preserving head reduction osteotomy combined with periacetabular osteotomy was good in one and moderate in the other up to three years after surgery; based on the pronounced hip destruction, the third received initially a total hip arthroplasty.ResultsThe described pathology is quite devastating, and extensive joint preserving surgery (which has been shown successful in Perthes’ cases) was less successful in this patient cohort.ConclusionSupraselective angiography may be helpful to improve pathomechanical understanding and surgical decision making.Cite this article: Bone Jt Open 2022;3(9):666–673.

Mesa redonda apresentada no Simpósio Internacional sobre Doença de Hodgkin, realizado no Instituto Nacional de Câncer no Rio de Janeiro — 16 a 20 de Janeiro de 1967. Transcrição da gravação não revista pelos autores.

This paper describes data from Asfaw at al. [1], which examined the eye movements of glaucoma patients (n=15) with pronounced asymmetrical vision loss (visual field loss worse in one eye). This allows for within-subject comparisons between the better and worse eye, thereby controlling for the effects of individual differences between patients. All patients had a clinical diagnosis of open angle glaucoma (OAG). Participants were asked to look at images of nature monocularly (free viewing; fellow eye patched) while gaze was recorded at 1000 Hz using a remote eye tracker (EyeLink 1000). Raw and processed eye tracking data are provided. In addition, clinical (visual acuity, contrast sensitivity and visual field) and demographic information (age, sex) are provided.

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin’s therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.

Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease associated with uncontrolled activation of alternative complement pathway. Obstetric aHUS, which develops in pregnant women and puerperas, is characterized by a particularly severe course with multiple organ failure, high death risk and end-stage renal disease. The prognosis of patients with obstetric aHUS has changed dramatically after the introduction of eculizumab, a monoclonal antibody to C5 complement component, into clinical practice. With timely initiation of the complement blocking therapy, the patients would not only survive, but also completely restore the function of the affected organs. Naturally, the question arises on the possibility of repeated pregnancies in women with previous obstetric aHUS and on the strategy of pregnancy management. The paper describes a clinical case of successful treatment with eculizumab for obstetric aHUS in the third trimester of the first pregnancy in a young and previously healthy woman, and the management of her second pregnancy. A 23-year old woman at 35-36 weeks of her first pregnancy developed the clinical picture of obstetric thrombotic microangiopathy, which was interpreted as a manifestation of severe preeclampsia and HELLP syndrome. However, after an emergency surgical delivery, the patient's condition continued to deteriorate despite the plasma exchange procedure. After exclusion of the other causes of thrombotic microangiopathy, aHUS was diagnosed and treatment with eculizumab was started, which resulted in complete recovery. No aHUS-associated mutations were identified. The complement inhibitor treatment was discontinued after 12 months. Four years after the first birth, the patient had a second pregnancy after preconception planning. During pregnancy, the patient was closely monitored for a timely identification of potential complications and had prevention of placental complications with acetylsalicylic acid and low molecular weight heparin. No aHUS recurrence and/or other complications were observed, and the patient did not require treatment with eculizumab during pregnancy. Elective caesarean section was performed at 39 week of gestation. A healthy boy was born with a bodyweight of 3370 g, a height of 50 cm, and Apgar score 8-9. In women with obstetric aHUS history, a favorable outcome of repeated pregnancies is possible, in some cases even without any prophylactic use of complement-blocking therapy, provided that with complete remission of aHUS has been achieved, with close monitoring during gestation and prevention of placenta-associated complications.

The article examines the semiotic features of the virtual narrative in the projects of RIA.Lab platform of the leading Russian news agency “Russia Today”. The aim is to analyze the structural, linguistic and iconic elements of the virtual narrative in relation to the projects of immersive journalism, highlighting their features, taking into account the multimodal nature of virtual reality and the simulative aspect of the sign system of immersive works. Virtual space is not only a narrative environment with special topos, chronotope and other narrative elements, but is itself a semiotic element, participating in the process of semiosis, the space of virtual “language game”. The thesis is put forward that VR, being an element of the multimodal information and communication universe, contains in its structure other modalities (TV, radio, cinema, print formats), and is multidimensional, a kind of “modus in modus”. The thesis on the priority of the modeling approach to the creation of immersive mass-media content over the simulative one and the necessity of observing the balance between modeling and simulation in immersive journalism are discussed. The specifics of conventional conditions of interpretation of simulacra signs in virtual space, which depend on the degree of their identity to the signs of real reality and the “rules of the virtual game”, set by the authors, are outlined. The directions of increasing the pragmatic efficiency of virtual narrative through the variability of its affords, the use of emphases, haptics (tactile experience) and other means of VR are outlined.

Introduction and Objectives: The functional dynamics of the gut microbiome and its interactions with the human transcriptome represent a niche for non-invasive biomarkers to risk-stratify MAFLD. This study aimed to identify gut transcriptomic signatures associated with MAFLD in Argentina. Materials and Methods: Stool samples, diet, demographic and clinical data were obtained from 33 biopsy-proven MAFLD patients (12 simple steatosis -SS- and 21 steatohepatitis -SH-) and 19 healthy volunteers (HV). RNA-seq was performed in NovaSeq6000®. Data were analyzed with Maaslin2-v1.2.0, bioBakery-v1.8 and DESeq2-v4.1. Co-expression analysis was performed with Hmisc-v4.7-0. Results: BMI was higher in MAFLD, particularly in SH patients (q=4.49 × 10−6). After adjusting for BMI, differentially expressed genes (DEGs) were found when comparing MAFLD vs. HV and SH vs. SS in bacterial (5 and 13, respectively), viral (112 and 26, respectively) and human (4 and 46, respectively), transcriptomes (q

The Mre11-Rad50 (MR) complex has key functions in the detection, signaling and repair of DNA breaks. Here the authors use transmission electron microscopy to show MR oligomerization is governed by a small beta-sheet protruding from the head domain of Rad50 at the base of the MR structure, and reveal MR head domain oligomerization is required for efficient DNA end resection.

Entrepreneurial activity of immigrants is a fairly new phenomenon for Russian reality which explains both the paucity of empirical works and the practically absence of a holistic view of theoretical and methodological foundations for such studies in Russian social science. The article aims to fill this gap and offer an analytical overview of the main foreign theoretical approaches to the immigrant entrepreneurship. The review is structured according to the main thematic issues in connection with which as a rule the peculiarities of immigrant entrepreneurship are discussed, which distinguish them from other types of entrepreneurship. The article sequentially examines approaches to the study of factors, group and individual characteristics of immigrants that promote or limit the development of their entrepreneurial activity; special attention is paid to the history of the study and (re)assessment of the role that ethnicity plays in migrant entrepreneurship; finally, the spatial aspect of the entrepreneurial activity of migrants is analyzed. Among the theoretical approaches special attention is paid to interactive theory, theory of mixed embeddedness, theory of ethnic economics, concepts of middleman, enclave economy, positioning, scaling and placement, as well as more modern concepts of glocalized networks, multifocality and transnational mixed embeddedness.

Introduction: The pharmacokinetics studies are some of the necessary parts of the drugs preclinical investigations. Pharmacokinetic properties of new peptide drug 1-deamino-arginine-vasotocin (dAVT) in the form of an injection solution for intravenous and intramuscular administration for hypernatremia correction were investigated. Materials and methods: The study was carried out on male rats and rabbits with a single intravenous administration of the drug in three doses, a single intramuscular administration in one dose and multiple administration to rats in one dose. To determine natriiuretic peptide concentration in blood plasma, tissues, and excretes, assays based on a sodium level change measurement using a biochemical analyzer have been developed and validated. Pharmacokinetic parameters were calculated by the model-independent method of statistical moments. Results and discussion: The pharmacokinetics of the drug was found to be linear after a single administration of dAVT drug in the dose range 3–10 μg/kg for rats and rabbits. The relative bioavailability of dAVT after intramuscular and intravenous administrations was more than 30%. After a biomarker content change, the active substance was intensively distributed into highly vascularized organs (spleen), the organs that provide metabolism and subsequent excretion (liver and kidneys), whereas it hardly reached moderately and weakly vascularized tissues (muscles, omentum). Less than 10% dAVT was excreted with urine; no dAVT was determined in feces; and repeated administration did not lead to its cumulation. Conclusion: Pharmacokinetics parameters of new nonapeptide drug 1-deamino-arginine-vasotocin were evaluated after original analytical biomarker approach. The study included all main areas necessary to characterize the original drug pharmacokinetic.