A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-Bampa) was validated using Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-Bampa were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for the 14 BCS class I-IV drugs cited in the FDA guidance (including other drugs as acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-Bampa. Apparent permeability (Papp) was compared to literature fraction dose absorbed in humans (Fa%). Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-Bampa performance. Mannitol and metoprolol Papp values across Franz-Bampa were lower (3.20 x 10-7 and 1.61 x 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 x 10-5 and 2.55 x 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed similar log linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-Bampa method for use during drug discovery process.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

Paratuberculosis, or Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa), however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the Centre-eastern region of Portugal were examined. Ninety-seven wild boar exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, poly-merase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5-56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to year-lings and adults (OR = 10.2, 95% CI: 2.2-48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

Medical records contain many terms which are difficult to process. Our aim in this study is to allow the visual exploration of the information in medical databases where the texts presents a large number of syntactic variations and abbreviations, through an interface which facilitates content identification, navigation and information retrieval. We propose the use of multi-term tag clouds as content representation tools and as assistants for the browsing and querying tasks. The tag cloud generation is achieved through a novelty mathematical method that allows related terms to remain grouped together within the tags To evaluate this proposal, we have used a database with 24,481 records. 23 expert users in the medical field were tasked to complete a survey to evaluate the generated tag clouds properties and we obtained a precision of 0.990, a recall of 0.870 and a F1score of 0.904 in the evaluation of the tag cloud as an information retrieval tool. The main contribution of this approach is that we automatically generate a visual interface over the text capable of capturing the semantics of the information and facilitating access to medical records.

With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) currently being developed and deployed to bolster access to personal protective equipment (PPE), patient treatment and diagnostics.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

The Eurasian grapevine (Vitis vinifera L.) is the most widely grown horticultural crop in the world and is important for the economy of many countries. In the wine production chain, grape varieties play an important role as they directly influence the authenticity and classification of the product. Identifying the different grape varieties is therefore fundamental for quality control and inspection activities, as well as for regulating production. Currently, ampelography and molecular analysis are the main approaches to identifying grape varieties. However, both methods have limitations. Ampelography is subjective and prone to errors and is experiencing enormous difficulties as ampelographers are increasingly scarce. On the other hand, molecular analyses are very demanding in terms of cost and time. In this scenario, Deep Learning (DL) and Machine Learning (ML) methods have emerged as a classification alternative to deal with the scarcity of ampelographs and avoid molecular analyses. In this study, the most recent and current methods for identifying grapevine varieties using DL classification-based approaches are presented through a systematic literature review. The classification pipeline of the 31 studies found in the literature was described, highlighting its pros and cons. Most of the studies used DL-based models trained with leaf images acquired in a controlled environment at a maximum distance of 1.2 metres to classify grape varieties. In addition, there is a large gap between practical applications and the datasets used: a great lack of varieties, limited data acquired in the field and a lack of tests on plants under adverse conditions. Potential directions for improving this area of research were also presented.

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central, South America. Thirty percent of the cases evolve into chronic cardiomyopathy (CCC) with worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate and severe CCC patients. MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with Brazilian healthy individuals. The European lineage is associated to protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. By mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of Chronic Chagas disease Cardiomyopathy.

Primary and secondary cardiovascular prevention is less effective than expected due to the concern about polymedication by professionals and the lack of patient adherence to medications prescribed in the medium and long term. Polypills have been presented as a possible solution. A comprehensive bibliographic review is presented about polypills as mechanisms for facilitating adherence and a proposed guide for the use of polypills for the prevention of cardiovascular risk. 41 articles were included, showing options for the polypill as a method of primary and secondary cardiovascular prevention.The polypill increases therapeutic adherence in the medium and long term, also increasing the therapeutic results compared to the administration of the various drugs separately. Based on the evidence, a flow diagram is proposed for the prescription of a polypill.Polypills increase the effectiveness and adherence of patients to primary and secondary cardiovascular prevention programs, without increasing the cost of the intervention. The use of a polypill in cardiovascular prevention can be effective as a prescription tool.

INTRODUCTION: Cardiovascular prevention is less effective than expected due to the concern about polymedication of professionals and the lack of adherence of patients. Polypills are presented as a possible solution, increasing therapeutic adherence in the medium or long term and improving therapeutic results compared to the administration of drugs separately: they increase effectiveness and Adherence of patients to primary and secondary cardiovascular prevention programs, without increasing the cost of the intervention. OBJECTIVES: Study #Trigeria: to specify the combined prevalence of Atrial Fibrillation, Dyslipidemia and Hypertension and analyze the pharmacological prescription for these pathologies and the possible indications and advantages that would have the prescription of a polypill for these risk factors.METHODS: Observational analytical study on the pathological history in elderly institutionalized in nursing homes and analysis of prescribed oral medication.RESULTS: 169 people analyzed (79.3% women) from 4 nursing homes; 8.9% had a history of Atrial Fibrillation, Dyslipidemia and Arterial Hypertension; these had a higher prevalence of heart disease (42.9%) and Cerebral Vascular Accident (35.7%). Polymedication was present in 88.5%, with an average of 6.94 oral drugs prescribed; among those with the three pathological antecedents, the average number of oral medications was 8.60. Only 26.7% of those with all three factors were prescribed drugs to control them.DISCUSSION: There are high rates of polymedication in the sample and low rates of prescription of antiplatelet agents in people with Atrial Fibrillation (26.5%); the low prescription of statins and antihypertensives of the ACE inhibitor or ARB-II groups may be due to good control with non-pharmacological measures or by the use of other groups of drugs . A polypill holding the drugs that control the three factors studied could increase the prescription rate while simplifying the administration schedule and reducing polymedication by 23.25% improving prescription, increasing adherence and control of risk factors without increasing pharmaceutical expenditure.CONCLUSIONS: There is a low rate of prescription of antiplatelet agents among people with atrial fibrillation. Combination methods (polypills) can increase the suitability of prescriptions in people with polypathology, improving prescribing, simplifying administration and increasing adherence to pharmacological treatments.

Chronic Chagas Cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilized electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodeling and for examining the potential of anti-parasitic drugs to prevent or alleviate CCC development and progression.

Parasitic diseases are among the most serious public health problems in developing countries, causing high mortality and economic burdens. The Trypanosomatidae family includes Leishmania spp. and Trypanosoma cruzi, which cause leishmaniasis and Chagas disease, respectively. Both these parasites are among the major agents of neglected tropical diseases (NTDs). Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization (WHO) records approximately 0.7-1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000-30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Despite the similarity of the parasites, the evolution of the disease and the clinical indexes are explicitly different in African, Asian, and American forms of infection. Clinical therapies are associated with drug resistance and side effects. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Peptide-based drugs are an attractive class of therapeutic agents. They are recognized for being highly selective and effective, as well as safe and well tolerated. Moreover, they are now being explored in the development of novel therapeutics for a variety of health disorders, including oncology, endocrinology, metabolic, cardiovascular, and bone diseases. In addition, they are being explored in tropical diseases such as leishmaniasis and Chagas disease. We will discuss current knowledge regarding the parasite life cycle, signs and symptoms, diagnosis, and treatment options for leishmaniasis and Chagas disease.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

In this work, nine fruits cultivated in the northern Amazon were studied: abiu, acerola, araçá, bacupari, biribá, caçarí, fruta-do-conde, graviola and taperebá, with the objective of carrying out a bromatological and nutritional study of the pulps of fruits studied. Of all of them, are the pulps of graviola (76.83 ± 0.02 kcal 100 g^-1) bacupari (76.83 ± 0.02 kcal 100 g^-1) and fruta-do-conde (46.66 ± 0.02 kcal 100 g^-1). Among the macronutrients, the high concentration of potassium stands out, especially in the graviola (541.16 ± 0.24 mg 100 g^-1) and the biribá (468.21 ± 0.13 mg 100 g^-1). Among the micronutrients, iron concentrations are representative for araçá pulp (3.04 ± 0.02 mg 100g-1), abiu is rich in zinc (3.71 ± 0.02 mg 100 g^-1) and manganese (6.61 ± 0.11 mg 100 g^-1). The presence of cobalt at the level of traces in some of the pulps studied stands out. The Pearson correlation coefficient was evaluated, as well as the statistical treatment by multivariate analysis PCA to establish the correlation between the variables studied.

Several plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in nature and have been utilized by man for pharmaceutical and agrochemical purposes. There are more than 3000 EOs reported in the literature with approximately 300 having commercial use, including the oils from Eucalyptus species. Such oils are rich in monoterpenes and have found applications as pharmaceuticals, agrochemicals, food flavorants and in the perfume industry. Such applications are related to their diverse biological and organoleptic properties. In view of their importance, we review in this article up to date information concerning chemical composition and biological activities of essential oils from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus¸ we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricide, insecticide and herbicide activities, hoping that such information will contribute in the advances of the research in this field. It is also intended that the information herein described can be useful in the rationalization of the use of Eucalyptus EOs as components for new pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

Reductions in water availability and increasing rainfall variability are generating a narrative of growing competition for water in the Mediterranean basin. In this article, we explore the distribution and importance of water resources in the Muga River Basin (Catalonia, Spain) based on key stakeholders’ perceptions. We performed a sociocultural evaluation of the main water ecosystem services in the region through stakeholder interviews and participatory mapping. The basin was generally perceived as a hotspot of ecosystem services, but we detected varying opinions and considerable differences in the perceptions of importance and spatial distribution of water ecosystem services. These discrepancies were linked to the varying levels of stakeholders’ dependence on water. Our findings are important for contributing to correct water planning and management in the river basin, which is a complex water social system marked by conflicts between different stakeholder groups vying for the same resource. This complex situation requires bottom-up strategies to create transparent, participatory decision-making models.

In 2020, the WHO established a road map for neglected tropical diseases 2021−2030 that aims to control and eradicate 20 diseases, including Leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions such as those caused by Trypanosoma cruzi and Leishmania spp infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, avoiding the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes, as well as to stimulate the host immune defenses or even serve as a vector of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of Leishmaniosis and Chagas disease.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, stands as a significant public health challenge in endemic regions of the Americas. Current treatment options, limited and associated with adverse effects, underscore the need for novel therapeutic approaches. This systematic review comprehensively examines existing research on natural products as potential agents against Chagas disease. Employing a systematic search strategy across diverse databases, studies meeting predefined inclusion criteria were assessed for methodological quality and relevance. The synthesis of findings reveals a spectrum of natural products showcasing promising anti-Trypanosoma cruzi properties. The review discusses the limitations of current evidence, highlights gaps in knowledge, and proposes avenues for future research. By elucidating the landscape of natural products in Chagas disease treatment, this review contributes to the ongoing pursuit of innovative and accessible therapeutic strategies.

Small ruminant lentivirus (SRLV) are infected and transmitted among ovine and caprine species. This disease is a severe problem for small ruminant production, not only for animals’ wellbeing but also for the herd’s efficiency. The main aim of this research was to quantify the seroprevalence and associated risk factors for SRLV infection in the north region of Portugal. Collected samples from a total of 150 herds, of which 129 (86.0%; 95% CI: 80.67% - 91.33%) had at least one seropositive animal. Out of 2607 individual blood samples, 1074 (41.2%) were positive for SRLV. The risk factors associated with SRLV infection were: specie (caprine), age (&gt; 2 years old), herd size (&gt; 100 animals), production system (intensive), production aptitude (milk), type of activity (professional), participation in livestock competitions (yes), buy replacement young ewe (yes) and rearing (natural). This knowledge empowers the implementation of effective preventive measures. Overall, biosecurity measures should be promoted and implemented to aim reducing viral transmission, with the main goal of reducing the prevalence of this disease. Completely, we understand that government authorities should promote and audit voluntary control and eradication programs in small ruminant herds in the region studied.

Angola is vulnerable to climate change, as most of its agriculture is rain-fed and repre-sents the backbone of the people of the southern region of the country, and many peo-ple’s livelihoods depend on it. All crops can suffer from the impacts of climate change, which can lead to challenges in agricultural production and food security in different regions of the world. The work consisted of a systematic review of the impacts of climate change on agriculture in Angola, particularly in the southern region. To achieve this objective the PRISMA2020 methodology was used, using the flowcharts for the selection of studies evaluated from the databases that are: Scopus and Web Sci-ence, resulting in 431 documents published between 1996 and 2023, and of these only 63 were included in the systematic review, with inclusion and exclusion criteria. Research on the short and long-term effects of climate change impacts in agriculture in Angola and in particular the southern region is scarce and insufficient. Temperatures are pre-dicted to rise and precipitation generally decreases over time (approximately -2% by 2100), with the southern region experiencing a stronger drop in precipitation. Agri-culture in Angola will be hit hard and some models show that agricultural productiv-ity will be up to 7% lower by 2050 owing to climate change.

Sustainability is a characteristic manifested in the ability to maintain the necessary level of performance for construction companies when risk factors arise during the implementation of investment and construction projects. The risk factors that arise during the implementation of in-vestment and construction projects differ in nature, degree of influence, and other characteristics. Ignoring these factors and measures to manage them often leads to critical consequences in the form of disruptions in the timing of work. Risk is a combination of the probability and consequences of the occurrence of adverse events. The article considers the concept of risk as a potential possibility of occurrence of adverse situations and related consequences when exposed to these factors. Risk factors are characterized by surprise, discreteness of changes, the presence of threshold values, upon reaching which a transition to a different mode of operation is required. The article discusses the risk factors arising at the construction stage, their classification. A methodology has been developed that includes conducting a survey in the form of a questionnaire in order to collect information about risk factors that affect the implementation of investment and construction projects. Experts with experience in the construction sector were involved in the survey. The processing of the survey results made it possible to assess the significance of various risk factors in investment and construction projects. Thus, statistical and expert methods were used in the study. The results showed that financial, technical, legal, economic, managerial and natural factors have the greatest impact on investment and construction projects. It is recommended to pay special attention to the listed factors when developing measures aimed at preventing risks and their consequences. The methodology described in the study can be used by construction companies in strategic planning. The analysis of the stability of construction companies, depending on their use of various ways to counteract risk factors, allowed us to develop a number of practical recommendations to reduce the impact of the studied factors on achieving the goals of investment and construction projects.

The center of mass dynamics of human seated posture in a work environment under hypogravity (0<g<1) have rarely been investigated and it remains to be accomplished. The present study determined the difference in the body system of 32 participants working under simulated 1/6g (Moon) and 1g (Earth) for comparison reason using static and dynamic action measurements. This was based on analyzing the participant's center of mass before, during, and after the task when they started to get fatigued. According to this analysis, there is a positive relation (p<0.01) with a positive coefficient of correlation between CoM body shift down along the Y axis and gravity level for males and females. At the same time, the same positive relationship (p<0.01) between the tilt of the body back along the Z axis and the level of gravity was found only in females. This offers fresh perspectives for comprehending hypogravity. It can also improve workplace ergonomics, body stability, equipment design, and biomechanics.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

The issue of actualization of labor interests as a motivational driver and one of the sources of labor productivity is little-studied in applied and organizational psychology. The study given in the paper fills some “blanks” of this problem. The leading approach to research is the motivational system proposed on the basis of theoretical analysis and the developed psychological model of labor interests. Using the methods of a special survey, questioning and interview guides, the analysis and comparative assessment of the labor interests of 50 candidates for the service manager position (entertainment and restaurant industry field) was conducted; as well as of 45 employees in this industry aged 18 to 25. The main results of the paper show the connection of labor interests with the company's personnel management system, namely with the processes of selection, adaptation, and training. It was revealed that the candidates selected for the service manager position were of primary group interest and financial incentive was secondary. At the same time, financial incentive contributed to the successful passage of the adaptation period. Occupational interests of employees depended on their education and job specifics. Career interests were influenced by the time spent with the company. The recommendations necessary for employers to create the conditions corresponding to the leading labor interests of employees were substantiated.

The paper provides information on significant contamination of real laboratory water with hydrophilic microimpurities. This fact suggests that researchers are practically dealing with microdispersed systems. However, this fact is usually neglected in the discussions of the causes of the anomalous properties of water. We will show that, when exposed to various factors of physical nature, water demonstrates reactions of the same type, namely, increased pH and electrical conductivity, reduced redox potential and viscosity, and enhanced bioavailability. Each exposure is accompanied by the destruction of aggregates of the dispersed phase and its transition to a fine-dispersed state. The relationship between this phenomenon and the change in the physicochemical properties of water is discussed.

Understanding the motor patterns underlying the movement of people with Parkinson's disease (PD) is fundamental to the effective targeting of non-pharmacological therapies. This study aims to analyze the gait pattern in relation to the evolutionary stage between I-II and III-IV according to the Hoehn and Yahr scale (H&amp;Y) in people affected by PD. The study was conducted with the participation of 37 PD patients, with a mean age of 70.09±9.53 years, and of whom 48.64% were women. The inclusion criteria were: 1. To be diagnosed with PD; 2. To be in an evolutionary stage of the disease of between I and IV and; 3. To be able to walk independently and without any assistance. Kinematic and spatial-temporal parameters of the gait were analyzed. The results show differences in speed of movement, cadence, stride length, support duration, swing duration, step width, walking cycle duration and double support time between the stages analyzed. These results confirm the differences in PD gait pattern between stages I-II and III-IV. Different behaviors of the same variable were recorded depending on whether the right or left sides were affected by PD.

A visible-light photoredox functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones through a Friedel-Crafts reaction with indoles using an inexpensive organophotoredox catalyst is described. The reaction uses a dual catalytic system formed by a photocatalyst simple and cheap, 9,10-phenanthrenedione, and a Lewis acid, Zn(OTf)₂. 5W white LEDs are used as visible-light source and oxygen from air as a terminal oxidant, obtaining the corresponding products with good yields. The reaction can be extended to other electron-rich arenes.

Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels and however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins at 10-8 M, Rn (10-6 M) and Ins+Rn (10-8 M and 10−6 M respectively) were added to astrocytes during 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. p-AKT, p-ERK, p-eNOS, Mn-SOD, COX-2, and the anti-inflammatory protein COX-2 were all upregulated by ins. On the contrary, no significant changes were found in the protein expression of Cu/Zn-SOD, NF-κB and IκB. The presence of Rn produced an increase in p-ERK protein and a significant decrease in COX-2 protein expression. Furthermore, Rn significantly increased the effects of Ins on the expression of p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ. On the other hand, Rn+Ins produced a significant decrease in COX-2 expression. In conclusion, Rn facilitated the effects of insulin on the p-AKT, p-eNOS, p-ERK, Mn-SOD and PPAR-γ, signaling pathways, as well as on the anti-inflammatory and antioxidant effects of the hormone.

Background: Zebrafish (Danio rerio) is a model organism emerged for the study of human cancer. Compared with the murine model, the zebrafish model has several properties ideal for personalized therapies. The transparency of the zebrafish embryos and the development of the pigment-deficient “casper” zebrafish line give the capacity to directly observe cancer formation and progression in the living animal. Automatic quantification of cellular proliferation in vivo is critical to the development of personalized medicine. Methods: A new methodology was defined to automatically quantify the cancer cellular evolution. ZFTool was developed to establish a base threshold that eliminates the embryo auto-fluorescence and automatically measures the area and intensity of GFP (green-fluorescent protein) marked cells and define a proliferation index. Results: Proliferation index automatically computed on different targets demonstrates the efficiency of ZFTool to provide a good automatic quantification of cancer cell evolution and dissemination. Conclusion: Our results demonstrate that ZFTool is a reliable tool for the automatic quantification of the proliferation index, being a measure of cancer mass evolution in zebrafish eliminating the influence of its autofluorescence.

Background Out-of-pocket costs are key expenses that many individuals incur in order to receive health services. They have been identified as a key access barrier for vulnerable populations, in particular for populations affected by neglected diseases with a chronic progression, such as Chagas disease. It is important to understand the costs of accessing healthcare services that are borne by patients with T. cruzi infection. Methodology We prepared a structured survey for patients with T. cruzi infection/Chagas disease who were all treated by the healthcare system in endemic municipalities in Colombia. The results were analyzed according to three categories: 1. the socioeconomic profiling of the patients; 2. the costs of and time spent on transportation; and 3. the opportunity costs (money that was not earned) related to treatment at the local primary care hospital or at the high-complexity reference hospital. Main findings Ninety-one patients answered the survey voluntarily. The data revealed that, when treated at the specialized reference hospital, patients spent 5.5 times more on food and accommodation, transportation costs were five times higher, and the loss of earnings was three times higher than when they were treated at the local primary care hospital. Moreover, the amount of time spent on transportation was 4 times higher at the reference hospital. Conclusions Providing comprehensive healthcare services for Chagas management at local primary healthcare hospitals would allow the most vulnerable patients to save on expenses related to medical and non-medical costs (out-of-pocket costs), in turn leading to higher adhesion to treatment thus benefiting the health system as a whole. These findings are in alignment with the WHO’s World Health Assembly 2010 Resolution on the importance of treating Chagas at local primary care hospitals, thereby saving patients time and money, allowing for timely care, and promoting access to healthcare.

It is shown that structuring at the microlevel is the intrinsic property of water and aqueous solutions. At room conditions water (including "ultrapure" one) and aqueous solutions are dispersed systems in which microcrystals of NaCl, surrounded by a layer of hydrated water (average diameter - 10-15 microns), are "elementary microparticles", which form the basis of the dispersed phase. Possible ways of formation of these microparticles and their evolution in the process of evaporation of unstructured part of water - dispersion medium - are considered. It is shown, in particular, that they are present in the air as aerosol contaminants. When the ionic strength of the solution increases, the water-salt particles coagulate, forming a new phase - coacervates, remaining on the substrate after evaporation of the liquid part of the water. The aggregates of coacervate structures, formed in a liquid medium, are disordered during heating, which can cause a change in a number of physicochemical properties of water at the temperatures of 50°-60°C range that have not been correctly explained in the framework of atomic-molecular concepts.

Powder mixture with given molar ratio Ca/P = 1.67 consisting of brushite (calcium hydrophosphate dihydrate) CaHPO4·2H2O, calcium oxalate monohydrate CaC2O4·H2O in form of whewellite and weddellite and some quantity of quasi-amorphous phase was obtained as a result of the interaction of hydroxyapatite powder Ca10(PO4)6(OH)2 with an aqueous solution of oxalic acid H2C2O4 at a molar ratio of Ca10(PO4)6(OH)2/H2C2O4 = 1:4 under mechanical activation conditions. This powder mixture was used to produce microporous monophase ceramics based on hydroxyapatite Ca10(PO4)6(OH)2 with aperient density of 1.25 g/cm3 after firing at 1200 oC. Microporosity of sintered ceramics was formed due to presence of particles with plate-like morphology, restraining shrinkage during sintering. Microporous ceramics based on hydroxyapatite Ca10(PO4)6(OH)2 with roughness of the surface as a consequence of the created microporosity can be recommended as a biocompatible material for the bone defects treatment and as a substrate for bone cell cultivation.

Smart Transformer (ST)-based Meshed Hybrid AC/DC Microgrids (MHM) are a feasible alternative to increase the performance of conventional microgrids (MG) and to increase the penetration of Distributed Energy Resource (DER) at the same time, active and reactive power dispatch on the system. Despite this, MHMs present challenges in managing resources under uncertainties and controlling electronic converters associated with the ST and DER, making it complex to achieve optimal system performance. In this paper, a Data-Driven Distributionally Robust Optimization (DDDRO) for Day-Ahead Operation Planning of an ST-based MHM considering the reactive power dispatch of the DER that minimizes network losses, voltage deviations, and operation cost simultaneously, considering uncertainties of Photovoltaic Generators (PVG) and demand, is proposed. The Column and Constraint Generation (C&amp;CG) algorithm and Duality-Free Decomposition (DFD) method are adopted. Besides, the original mixed-integer non-linear planning problem is converted into a Mixed-Integer (MI) Second-Order Cone Programming (SOCP) problem through second-order cone relaxation and positive octagonal constraint method. Simulation experiments and results with a connected MHM system demonstrate the effectiveness and performance of the proposed model. Finally, we observe the effect of the meshed structure of MG and the positive impact of integrating the ST to form MHM, taking advantage of the degrees of freedom of this multi-stage converter for optimal energy management under uncertain conditions.

In this work, the wetting and evaporation behaviour of non-polar solvent droplets on thin soluble coatings is investigated experimentally. The wetting process on spin coated polymer layers by the solvent is captured using shadowgraphy. Initial spontaneous dynamic wetting as well as later stages of wetting are recorded and evaluated. Furthermore, structures obtained by wetting and subsequent evaporation of solvents on polymer coatings are studied by confocal microscopy. The solubility of the substrate has been varied by using polymers with different molecular masses. We observe that initial spreading dynamics does not depend on the molar mass in the studied range. However, we find a strong influence of the molar mass on the late stage wetting dynamics and on the surface structure after solvent evaporation.

This paper describes the preparation and description of four new complexes [Bu₂Sn(AA)Cl] (AA = glycine, DL-valine and L-leucine) and [Bu₂SnPhen₂] (Phen = DL-phenylalanine) They were characterized by elemental analyses of carbon, hydrogen, nitrogen, chlorine and tin; and by infrared, ^119mSn-Mössbauer and ^119mSn-RMN spectroscopies, and by the applications of TG and DSC techniques in dynamic helium atmosphere. For the [Bu₂Sn(AA)Cl], trigonal bipyramidal tin species, AA were coordinated bidentatedly by the carboxylic oxygen and by the NH₂ group. The [Bu₂SnPhen₂)], with tin atoms in trans-octahedral sites, had the Phen-coordinated by both carboxylic oxygen atoms.

Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals in Europe, Asia, and North America. In this study, we aimed to characterize circulating EVs derived from patients with chronic Chagas disease (CCD) experiencing reactivation of acute symptoms. Blood samples collected in EDTA were processed to isolate plasma and subsequently subjected to ultracentrifugation for particle isolation and purification. The EVs were characterized using nanoparticle tracking analysis and enzyme-linked immunosorbent assay (ELISA). Our findings revealed distinctive differences in size, concentration, and composition of EVs between immunosuppressed patients and those with CCD. Importantly, these EVs play a critical role in the pathophysiology of Chagas disease and demonstrate significant potential as biomarkers in the chronic phase of the disease. Overall, our findings support the potential utility of the CL-ELISA assay as a specific sensitive tool for detecting circulating EVs in chronic chagasic patients, particularly those with recurrent infection following immunosuppressive treatment or with concurrent HIV and Chagas disease. Further investigations are warranted to identify and validate the specific antigens or biomarkers responsible for the observed reactivity in these patient groups, which may have implications for diagnosis, monitoring of treatment and prognosis.

Wearable cardiac sensors pave the way to advanced cardiac monitoring applications based on heart rate variability (HRV). In real-life settings, heart rate (HR) measurements are subject to mo-tion artifacts that can be timely removed from the recordings. This leads to frequent data loss in the HR signal, especially for commercial devices based on photoplethysmography (PPG). The cur-rent study had two main goals: (i) to provide a white-box quality index that estimates the amount of missing samples in any piece of HR signal; and (ii) to quantify the impact of data loss on feature extraction in a PPG-based HR signal. This was done by comparing real-life recordings from com-mercial sensors featuring both PPG (Empatica E4) and ECG (Zephyr BioHarness 3). After an out-lier rejection process, our quality index was used to isolate portions of ECG-based HR signal that could be used as benchmark, to validate the output of Empatica E4 at the signal level and at the feature level. Our results showed high accuracy for estimating the mean HR, poor accuracy for short-term HRV features and moderate accuracy for longer-term HRV features. Levels of error could be substantially reduced by using our quality index to identify time windows with few or no missing data.

Background: Chagas disease is still a neglected disease considered a public health problem. Early diagnosis of cases is important to improve the prognosis of infected patients and prevent transmission. Serological tests are the method of choice for diagnosis. However, two serological tests are currently recommended to confirm positive cases. In this sense, more sensitive and specific serological tests need to be developed to overcome the problems currently faced. This study aimed to develop a new recombinant multiepitope protein for the diagnosis of Chagas disease, hereafter named rTC. Methods: The rTC was constructed based on amino acid sequences from different combinations of Trypanossoma cruzi antigens in the same polypeptide and tested in ELISA for detecting different Chagas disease. Results: rTC1 was able to discriminate between indeterminate (IND) and cardiac (CARD) cases and cross-reactive diseases, and healthy samples, with 96.6% sensitivity and 97.96% specificity, respectively. Conclusion: These data suggest a preliminary study that rTC1 has the po-tential to be tested in future studies against a larger serological panel for the diagnosis of Chagas disease.

Economic burden due to premature mortality has a negative impact not only in health system even though in the society. The aim of this study was to estimate the potential years of work tenure lost (PYWL) due to Chagas disease in Colombia from 2010-2017. National data on mortality by sex and ages between 15 and 62 dues to Chagas from 2010 to 2017. The PYWL methodology was applied to assess the impact of Chagas disease in workers who suffer from them. In total, 1,261 deaths were analyzed in the study, of which 60% corresponded to males. The loss of labor productivity caused by Chagas disease was estimated at $29 million. Overall, 48,621 PYWL were lost, and there was an average of 21 years for all subjects with Chagas. Throughout the analyzed period, PYWL increased substantially, and it is necessary to continue with early detection programs to avoid premature death in working age population.

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor (P-elF2α) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

Vienna Atomic Line Database (VALD) contains data on atomic and molecular energy levels and parameters of spectral lines required for stellar spectra analysis. Hundreds of millions lines for fine spectral synthesis and for opacity calculations are collected in present version of VALD (VALD3). Critical evaluation of the data and the diversity of extraction tools support high popularity of VALD among users. The data model of VALD3 incorporates obligatory links to the bibliography making our database more attractive as publishing platform for data producers. The VALD data quality and completeness are constantly improving allowing better reproduction of stellar spectra. To illustrate continuous evolution of the data content we present a comparative analysis of the recent experimental and theoretical atomic data for Fe-group elements, which will be included in the next VALD release. This release will also include a possibility for extracting the line data with full isotopic and hyperfine structures.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

The famous Capital Asset Pricing Model (CAPM) takes into account only business risk. In practice, companies use debt financing and operate at non–zero levels of leverage. This means that it is necessary to take into account the financial risk associated with the use of debt financing along with business one. The purpose of this paper is to simultaneously take into account the business and financial risk. A new approach to CAPM has been developed that takes into account both business and financial risk. We combine the theory of CAPM and the Modigliani–Miller (MM) theory. The first is based on portfolio analysis and accounting for business risks in relation to the market (or industry). The second one (the Modigliani–Miller (MM) theory) describes a specific company and takes into account the financial risks associated with the use of debt financing. The combination of these two different approaches makes it possible to take into account both types of risks: business and financial ones. We combine these two approaches analytically, while Hamada did it phenomenologically. Using the Modigliani–Miller (MM) theory, it is shown that the Hamada’s model, first model, used for this purpose half a century ago, is incorrect. In addition to the renormalization of the beta–coefficient, obtained in the Hamada model, two additional terms are found: the renormalized risk–free return and the term dependent on the cost of debt kd. A critical analysis of the Hamada model was carried out. The vast majority of listing companies use debt financing and are levered, and the Hamada model is not applicable to them in contrast to a new approach applicable to leveraged companies. Implemented a new approach to specific companies. A comparison of the results of the new approach with the results of the conventional CAPM is shown. Two versions of CAPM (market or industry) are considered.

The paper presents the reconstruction of paleoenvironmental conditions in the Gdansk, Bornholm and Arcona Basins of the Baltic Sea over the last millennium. A complex study (including geochemical, XRF, grain size, AMS and micropalaeontological analyses) of five sediment cores, retrieved by short gravity corer of Niemistö type, was performed. The cores are mainly represented by undisturbed silty muds of olive-grey and grey colours. The age models for the cores were built based on Pb distribution along the sediment sequences as radiocarbon dating resulted in excessively old age. Despite generally very low foraminiferal amount and diversity the increased inflow activity was reconstructed during the Medieval Climate Anomaly. The strongly positive North Atlantic Oscillation (NAO) index during this period led to a prevalence of westerlies over the Baltic region and stronger saltwater intrusions. In the recent sediments, the reconstructed inflow frequency demonstrates a decadal variability rather than the reduction, although, the general decline compared to the Medieval Climate Anomaly is seen.

In the current pilot study, we attempt to find out how double neurofeedback influences functional hemispheric asymmetry and activity. We examined 30 healthy participants (8 males; 22 females, mean age = 29; SD= 8). To measure functional hemispheric asymmetry and activity, we used computer laterometry in the ‘two-source’ lead-lag dichotic paradigm. Double biofeedback included 8 minutes of EEG oscillation recording with five minutes of basic mode. During the basic mode, the current amplitude of the EEG oscillator gets transformed into feedback sounds while the current amplitude of alpha EEG oscillator is used to modulate the intensity of light signals. Double neurofeedback did not directly influence the asymmetry itself but accelerated individual sound perception characteristics during dichotic listening in the preceding effect paradigm. Further research is needed to investigate the effect of double neurofeedback training on functional brain activity and asymmetry taking into account participants’ age, gender, and motivation.

Titanium dioxide (TiO2) thin films have been widely used in transparent optoelectronic devices owing to their excellent optical properties also is used in photocatalysis, cosmetics, and many other biomedical applications. However, a lack of studies was published on microstructure and adherence comparison of the TiO2 deposited on both AISI substrates. In this work, TiO2 thin films were deposited onto AISI 304 and AISI 316L stainless steel (SS) substrates via atomic layer deposition. Its heterostructure, morphology, and adhesion were compared in both substrates looking for synergistic and multifunctional properties. Raman spectroscopy mapping and X-ray diffraction using the Rietveld refinement method showed that the films are composed of anatase and rutile phases in different percentages. Scratching tests were used to analyze the film adher-ence and friction between a diamond tip and TiO2 film, showing well adhered in both substrates.

Introduction: The primary objective of researchers in the biology of ageing is to gain a comprehensive understanding of the ageing process while developing practical solutions that can enhance the quality of life for older individuals. This involves a continuous effort to bridge the gap between fundamental biological research and its real-world applications. Purpose: In this narrative review, we attempt to link research findings concerning the hormetic relationship between neurons and germ cells, and translate these findings into clinically relevant concepts. Methods: We conducted a literature search using PubMed, Embase, PLOS, Digital Commons Network, Google Scholar and Cochrane Library from 2000 to 2023, analyzing studies dealing with the relationship between hormetic, cognitive, and reproductive aspects of human ageing. Results: The process of hormesis serves as a bridge between the biology of neuron-germ cell interactions on one hand, and the clinical relevance of these interactions on the other. Details concerning these processes are discussed here, emphasizing new research which strengthens the overall concept. Conclusions: This review presents a scientifically and clinically relevant argument, claiming that maintaining a cognitively active lifestyle may decrease age-related degeneration, and improve overall health in ageing.

Hormone changes across women's menstrual cycle may lead to changes in perception of chemical signals and hormonal responses to these cues. The aim of the present study was to determine the role of menstrual cycle phase on the effects of extracts of male axillary secretions (EMAS) in women. We tested healthy reproductive age and premenopausal women (n=29). EMAS/control solution was applied once in two hours either in the follicular or luteal phase, while collecting saliva samples for LH and cortisol monitoring. LH and cortisol concentrations were analyzed using EIA technique. PANAS and VAS were used to assess the mood. We observed a significant increase in the number of LH peaks (p=0.0447) and their amplitude (p=0.0469) when EMAS was applied in the follicular phase. The same application in the luteal phase lowered the amplitude of LH peaks (p=0.0382). EMAS application increases salivary cortisol level in reproductive age women relative to premenopausal women (p=0.0032). PANAS revealed changes in positive and negative affect after EMAS application. Our data indicate the significance of the menstrual cycle phase for EMAS effects on LH secretion, mood, but not on cortisol secretion in women.

In the research we consider a structure-fluid interaction of oscillating piezodevice and acoustic liquid. Such problem requires finding resonance or anti-resonance frequencies of the solid structure to use them in the latter frequency-response analyses step. After finite element discretization of the issue, we need to solve a generalized eigenvalue problem (GEP). The most efficient numerical method for solving the partial GEP is the shift-and-invert Lanczos method. Each step of this algorithm requires solving a large scale system of linear algebraic equations (SLAEs) with special properties. Various ways of ordering grid nodes lead to coefficient matrices with different structure. Several methods are compared in terms of efficiency. The results of the numerical experiments are presented.

The paper is focused on researching the behavior of heating companies in connection with current developments in the electricity market and flexibility in the context of market behavior. The work assesses the increase in profitability through the creation of a technical-economic model using an objective function with profit maximization. The paper objective is presented the procedure and methodology for creating a model using the basic scheme of production processes integrated into the system platform. The result of the work is a comparative analysis of modelled cases of implemented operation deployment according to a defined period and modelling modes in selected time series. The description of individual outputs demonstrates the economic advantage of using combinations of modes of combined electricity and heat production, and non-combined electricity and heat production, including the use of the heat suppression mode because of overproduction of electricity.

The combined ecological, geophysical, climatic, and social factors of the Northeast of Russia influence the organism from the early childhood being too intense for the functional systems. The purpose of the research is to study the emotional characteristics of adolescents of different ethnic groups in the northeast of Russia. Presented in the paper are results of the study that covered 826 adolescents (445 females and 381 males) at the age of 15–17, different by ethnic origin. We used standard methods of psycho-diagnostics. Our study has showed that the formation of the adolescents’ emotional sphere in the North is undoubtedly influenced not only by the climatic and socio-economic environmental factors but also by ethnic features. There are intergroup differences in the aggressiveness profile of older adolescents living in the remote settlement vs. the regional center. It is shown that high school students in the remote settlement of Evensk, compared to their peers in Magadan, regardless of gender and ethnicity, are characterized by more pronounced hostile and auto-aggressive reactions. In adolescents of the Aboriginal population, as compared with their age mate Caucasians, the indicators of impairment in the field of Neuro Psychic Adaptation, Situational and Personal Anxiety, and Social Frustration are significantly more pronounced.

In Malaysia, as in many parts of the world, vocational education and training (VET) is frequently perceived as the solution to improving the opportunities of youths who lack the resources, skills or motivation to continue with higher education. The focus of the study falls on the effectiveness of the apprenticeship scheme during the 10^th Malaysia Plan. This study may provide an opportunity to find out how the related parties react towards the apprenticeship scheme. This is important, as feedbacks are central to the success or failure of any scheme. It is expected that the relevant government bodies, private sectors, trainers and trainees will have a valuable insight on the progress this far and what need to be done in the future based on the outcome of the research. This study follows snowballing sampling method and gathers the information from apprentices from variety of industrial sectors. The findings indicate effectiveness at some types of training but lacks comprehensiveness and efficient use of resources and future direction, especially during the 10^th Malaysia plan period from 2011 to 2016. This exploratory research is a first chapter of the deeper study in this niche.

Removal of the proliferation component of gene expression by PCNA adjustment has been addressed in numerous survival prediction studies for breast cancer and all cancers in the TCGA. These studies indicate that widespread co-regulation of proliferation upwardly biases survival prediction when gene selection is performed on a genome-wide basis. In addition, removal of the correlative effects of proliferation does not reduce the random bias associated with survival prediction using random gene selection. Since most cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we pursued an investigation to remove the proliferation component of expression in DNA repair genes to determine survival prediction. This translational hypothesis-driven focus on DNA repair genes is directly amenable to finding new sets of DNA repair genes that could potentially be studied for inhibition therapy. Overall survival (OS) prediction was evaluated in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene expression were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Interestingly, PARP1 was not a significant predictor of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic cancers for inhibition therapy may be AML, colorectal, and renal papillary, because of potentially less confounding due to lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer for inhibition therapy is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications in DNA repair genes. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.

The rapid development of algorithms for skeleton detection with relatively inexpensive contactless systems and cameras opens the possibility of virtual exercise therapy for patients with different complications. However, evaluation and confirmation of posture classifications is still needed. The purpose of this study was therefore to find the most accurate algorithm for automatic classification of human exercise movement. A Kinect V2 with 25 joints identification was used to record movements for data analysis. A total of 10 subjects volunteered for this study. Four algorithms were tested for the classification of different postures in Matlab. These were based on: total error of vector lengths, total error of angles, multiplication of these two parameters and simultaneous analysis of the first and second parameters. A base of 13 exercises was then created to test the recognition of postures by the algorithm, and to analyse subject performance. The best results for posture classification was shown by the second algorithm with an accuracy of 94.9%. The average correctness of exercises among the 10 participants was 94.2% (SD1.8%). The algorithms tested in this study therefore proved to be effective and could potentially form the basis for developing a system for remote monitoring of rehabilitation involving exercise.

The aim of this study is to explore the extent of English language teaching in Higher Institutions of Malaysia and investigate the current changes, trends and challenges in this niche. A sample of 100 English learners from public and private institutions participated in this study. Analysis of the responses indicated that English language is remaining to be difficult to master, due to speaking environment, proficiency of the teachers and other factors. However, the Government is on the right direction to improve this situation by following Common European Framework of Reference of Languages. As any other system, it takes time to put into realization and start up the mechanism. This observation carries a pedagogical perspective and includes the overview of the general picture based on Private, Public and Stand Alone English educational institutions. This study has highlighted the practical importance of British Framework of English learning and suggests to focus on emphasis of the learning process instead of a result.

The adoption of algorithms based on Artificial Intelligence (AI) has been rapidly increasing during the last years. However, some aspects of AI techniques are under heavy scrutiny. For instance, in many use cases, it is not clear whether the decisions of an algorithm are well-informed and conforming to human understanding. Having ways to address these concerns is crucial in many domains, especially whenever humans and intelligent (physical or virtual) agents must cooperate in a shared environment. In this paper, we introduce an application of an explainability method based on the creation of a Policy Graph (PG) based on discrete predicates that represent and explain a trained agent’s behaviour in a multi-agent cooperative environment. We show that from these policy graphs, policies for surrogate interpretable agents can be automatically generated. These policies can be used to measure the reliability of the explanations enabled by the PGs, through a fair behavioural comparison between the original opaque agent and the surrogate one. The contributions of this paper represent the first application of policy graphs in the context of explaining agent behaviour in collaborative multi-agent scenarios and presents experimental results that sets this kind of scenario apart from previous application in single-agent scenarios: when requiring collaborative behaviour, predicates that allow representing observations about the other agents are crucial to replicate the opaque agent’s behaviour and increase the reliability of explanations.

Postpartum depression is a significant health issue during the postpartum period and not only affects the woman but also has important repercussions for the newborn. Group support interventions during the postpartum period have proven effective in helping women cope with depression and improving breastfeeding rates. The aim of this study was to assess the effectiveness of a midwife-led breastfeeding support group intervention on breastfeeding rates, postpartum depression and general self-efficacy. This was a multicentric cluster randomized controlled trial with control and intervention groups and was not blinded. It was conducted in Andalusia (southern Spain) from October 2021 to May 2023. A total of 382 women participated in the study. Results showed a significant difference in exclusive breastfeeding rates at 4 months postpartum between the groups (p &lt; 0.001). Additionally, there was a lower mean score on the Edinburgh Postnatal Depression Scale in the intervention group (12.49 ± 3.6 vs 13.39 ± 4.0; p = 0.044). Similarly, higher scores of general self-efficacy were observed among breastfeeding women at 2 and 4 months postpartum (p = 0.002 and p &lt; 0.001, respectively). In conclusion, midwife-led breastfeeding support groups enhanced self-efficacy, prolonged breastfeeding and reduced postpartum depression 4 months after giving birth.

Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American Trypanosomiasis (Chagas Disease). Although its precise mechanisms are not yet fully understood, miltefosine exhibits broad-spectrum anti-parasitic effects primarily by disrupting the intracellular Ca2+ homeostasis of the parasites while sparing the human hosts. In addition to its inhibitory effects on phosphatidylcholine synthesis and cytochrome c oxidase, miltefosine has been found to affect the unique giant mitochondria and the acidocalcisomes of parasites. Both of these crucial organelles are involved in Ca2+ regulation. Furthermore, miltefosine has the ability to activate a specific parasite Ca2+ channel that responds to sphingosine, that is different to its L-type VGCC human ortholog. Here, we aimed to provide an overview of recent advancements of the anti-parasitic mechanisms of miltefosine. We also explored its multiple molecular targets and investigated how its pleiotropic effects translate into a rational therapeutic approach for patients afflicted by Leishmaniasis and American Trypanosomiasis. Notably, miltefosine's therapeutic effect extends beyond its impact on the parasite to also affect positively the host's immune system. These findings enhance our understanding on its multi targeted mechanism of action. Overall, this review sheds light on the intricate molecular actions of miltefosine highlighting its potential as a promising therapeutic option against these debilitating parasitic diseases.

Background: School meals represent a significant supply of nutrients for children in Brazil, especially those in conditions of social vulnerability. Objectives: This study aimed to assess the levels of arsenic (As), cadmium (Cd), and lead (Pb) in meals served in public elementary schools in four municipalities in the state of Bahia, Brazil, and assess the risk posed to children's health. Methods: Ninety-six samples were collected from 16 schools, freeze-dried, and subjected to microwave-assisted digestion. The As, Cd, and Pb levels were determined by graphite furnace atomic absorption spectrometry. The risk assessment was based on calculating each element's hazard quotient (HQ). Results: None of the samples reached or exceeded the tolerable levels for the elements analyzed. Pb was the metal that obtained the most significant result, reaching maximum levels of 39-157 µg.kg-¹. Conclusions: No element exceeded the PTWI proposed by JECFA; thus, the toxic metal content in school meals poses a negligible risk to children´s health.

The purpose of our study is to determine the effectiveness of various types of psychocorrection measures: social and psychological training, a method of biological feedback and Sandplay for the indicators of childhood anxiety among younger schoolchildren. The study was conducted in the school of Magadan, North East of Russia (9-10 year old students, n = 43). We used a standardized method of Multidimensional Assessment of Child Anxiety which included 10 scales. The correction methods were used: socio-psychological training (SPT), biofeedback method (BFB), individual and group Sandplay. Students of group I (n = 12) participated only in the SPT. Students of group II (n = 11) participated in the SPT and underwent a course of training in self-regulation using the BFB method. In correction work with the students of group III (n = 20), the SPT, BFB, individual and group Sandplay were used. In group I, after the correction activities, a significant decrease in anxiety was observed in 3 of 10 scales (2, 6, 7; (p <0.05). In group II it was seen in 5 scales (1, 3, 6, 7, 8; p <0.05). In group III, a significant improvements took place in 7 scales (1, 2, 5, 6, 7, 9, 10; p <0.01–p <0.05). The present study has shown the different efficacy of applying the remedial techniques separately and in combination. The use of methods in the complex enhances the impact on the types of the child anxiety.

This study presents head losses (hL) and loss coefficients (K) obtained experimentally for schedule 40 PVC pipe elbows, with 90o and 45o in small commercial diameters of ½ to 1½ inches that are commonly used in small networks. The investigation was conducted on a system constructed with short pipes and fittings necessary to measure, direct, and control flow, as well as to evaluate pressure head losses at elbows. Simple water flow was used with rates of 0.342 to 0.980 lps (Q), which generated moderate Reynolds numbers (Re) of 13337 to 80221. It was found that hL showed dependence on the velocity head in all elbows, as well as that hL are greater as the diameter increases for same velocity head. The K values in the elbows tended to be constant when Q &gt; 0.75 lps, but for Q &lt; 0.75 lps the K coefficient increased inversely proportional to Q, becoming larger as the diameter increased. Likewise, the K coefficient tended to increase as Re decreased, while K tended to be constant as Re increased. The results of the experimental coefficient were compared against K values reported in the literature, where significant similarities and discrepancies were found.

Background. Neoplastic diseases and infections have become the leading causes of death in SLE in recent decades. Cancers and infections were also precipitating factors in the development of catastrophic APS. Case summary. We describe two patients: one of them had definite antiphospholipid syndrome (APS) and melanoma and the other had definite systemic lupus erythematosus (SLE) with APS, melanoma, infiltrative tuberculosis and severe Herpes Zoster (HZ). Management of patients with SLE concurrent with APS is a rather difficult task in rheumatology practice. In addition to kidney damage and cardiovascular disease, infections and malignancies are a significant cause of death in this cohort. The risk of malignancy in SLE is of considerable interest, since the immune and genetic pathways underlying the pathogenesis of this disease, as well as the immunosuppressive therapy, can significantly alter the risk. Both patients still had reliable APS, confirmed by triple-positive aPL. Both were at high risk of thrombosis. Patients ' adherence to treatment with direct oral anticoagulants and relapse of thrombosis on the background of rivaroxaban were noted. Conclusion. The cases where cancer or tuberculosis develops in the presence of rheumatic diseases are not so common and complicate the possibilities of therapeutic approaches, limiting the use of drugs that are not regulated by clinical recommendations.

Viruses with encephalitogenic potential can cause neurological conditions of clinical and epidemiological importance, such as Saint Louis encephalitis virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, dengue virus, Zika virus, Chikungunya virus, Mayaro virus and West Nile virus. The objective of the present study was to determine the number of arboviruses with neuroinvasive potential isolated in Brazil that corresponds to the collection of viral samples belonging to the Section of Arbovirology and Hemorrhagic Fevers (SAARB/IEC) of the Laboratory Network of National Reference for Arbovirus Diagnosis from 1954 to 2022. A total of 1,090 arbovirus samples with encephalitogenic potential were isolated from mice. From a total of 7,054 samples intended for cell culture. The isolates from mosquitoes totaled 659 viruses. The emergence of new arboviruses may be responsible for diseases still unknown to humans, making the Amazon region a hotspot for infectious diseases due to its fauna and flora species characteristics. The detection of circulating arboviruses with the potential to cause neuroinvasive diseases is constant, which justifies the continuation of active epidemiological surveillance work that offers adequate support to the public health system regarding the virological diagnosis of circulating arboviruses in Brazil.

Intense rainfall events frequently occur in Brazil, often leading to rapid flooding. Despite their recurrence, there is a notable lack of sub-daily studies in the country. This research aims to assess patterns related to the structure and microphysics of clouds driving intense rainfall in Brazil, resulting in high accumulations within 1 hour. Employing a 40 mm/h threshold and validation criteria, 83 events were selected for study, observed by both single and dual-polarization radars. Contoured Frequency by Altitude Diagrams (CFADs) of reflectivity, Vertical Integrated Liquid (VIL), and Vertical Integrated Ice (VII) are employed to scrutinize the vertical cloud characteristics in each region. To address limitations arising from the absence of polarimetric coverage in some events, three case studies focusing on polarimetric variables are included. A fourth case study enhances the overall understanding of these events, emphasizing the underexplored nature of short-term intense rainfall studies in Brazil. Results reveal that the generating system significantly influences the rainfall pattern, especially in the Southern, Southeastern, and Central-Western regions. Regional CFADs unveil primary convective columns with 40-50 dBZ reflectivity, extending to approximately 6 km. The microphysical analysis highlights the rapid structural intensification, challenging the event predictability and the issuance of timely specific warnings.

By using a two-stage physiologically based extraction test (PBET) and (W-PBET), the authors of this paper have estimated the bioaccessibility of metals (Pb and Fe) and their compounds in the GI tract of waterfowl and mammals. It has been shown that the metals (Pb and Fe) have low bioaccessibility; combined with the short time of shot exposition at the GI tract, this eliminates the risk of toxic effects in the case of shot ingestion by waterfowl. It has also been discovered that there is a significant difference in the bioaccessibility of metals and their compounds. A model was proposed and tested to predict the toxic effects of lead on biological objects depending on the threshold mass of consumption. This model takes into account data on the bioavailability of lead and regulatory values indicating dangerous concentrations of lead.

Effective waste elimination is critical for the success of construction projects. Although several studies have focused on various aspects of construction waste, limited efforts have investigated the dynamic effect of Making-Do (MD) practices on productivity, rework, defects, and materials wastage. From a lean construction perspective, this study aims to address MD waste using the Last Planner System (LPS) and BIM. First, the casual structure that can cause MD in construction projects was expressed in a casual loop diagram (CLD), and thematic analysis uncovered the strategies of LPS-BIM to eliminate MD identified by reviewing the literature. Secondly, twenty-five strategies from the LPS and BIM strategies to address MD using Structural Equation Modeling (SEM) were assessed. Subsequently, a system dynamics model (SDM) for investigating LPS-BIM strategies on MD decisions in a construction project was formulated based on the underlying causal loop diagrams and the mathematical relations among the variables. Finally, the model was applied to three projects, and simulations for four LPS-BIM scenarios were carried out. The findings show that dynamic interactions among diverse production planning and control factors are critical in evaluating MD impacts on a construction project. The results demonstrate that the LPS-BIM approach resulted in an average 43.8% reduction in the tasks performed with MD, 45.3% of constraints, 66.5% of construction waste, increasing 13.7% completion rate, and 29.3% cost reduction, demonstrating that LPS-BIM as a more efficient solution for MD mitigation and construction planning.

Biocompatibility of ceramic materials in CaO-P2O5 system was investigated using different methods, including in vitro and in vivo tests. Ceramics based on calcium pyrophosphate Ca2P2O7 were obtained by annealing cement-salt stone from highly concentrated hardening suspensions (HCHS). Cement-salt stone was prepared using powder mixtures of calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2·H2O. These salts were mixed with each other in such a way that calcium pyrophosphate and calcium polyphosphate were present in the final ceramic product in the following weight ratios: Ca(PO3)2/Ca2P2O7 = 0/100; 5/95; 10/90 and 20/80. Distilled water was added to a homogenized powder mixtures of Ca3(C6H5O7)2·4H2O and Ca(H2PO4)2·H2O by a water/solid ratio of 0,5 by weight. The obtained suspensions were shaped using silicon molds and left to dry in air for a week. The phase composition of the obtained samples of cement-salt stone was represented by brushite CaHPO4·2H2O, monetite CaHPO4, calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate Ca(H2PO4)2·H2O. According to the XRD data, the phase composition of ceramic materials after annealing in the temperature range of 800-1000 0C was mainly represented by the β-Ca2P2O7 phase. In vivo tests shown that obtained ceramic materials can be recommended for regenerative treatments for bone defects.

Background: The prevalence of atopic dermatitis in domestic animals is one of the problems of modern veterinary. Treating with standard techniques using chemotherapeutic agents not always leads to a positive result of therapy; moreover, many drugs produce adverse side effects. Methods: Low level laser therapy, in particular, intravenous laser blood illumination (ILBI) has a pronounced and long-lasting impact on the immune system of animals. The combined technique including ILBI-635 (635 nm, 2 mW, 5 min) and LUVBI^® (365 nm, 2 mW, 3 min) every other day provides a positive change in clinical status of cats with allergic dermatitis after the 3rd-4th treatment session. Results: The increased level of erythrocytes and hemoglobin was identified in the course of treatment, and it indirectly indicates increased blood transport activity, which improves trophic provision and microcirculation. A double reduction of leukocytes and a significant decrease of neutrophil cells indicate the immunomodulatory effect of LILI (low-intensity laser illumination). The increase in the percentage of lymphocytes and the decrease of eosinophils and monocytes against the background of basophil concentrations deviations within physiological concentration result in the reduction of inflammatory mediators expression that induce itching. The reduction of total IgE concentration 32 times against control on the 7th day of treatment correlates with the decrease in the quantitative content of peripheral blood eosinophils, indicating the decrease in severity of an allergic process. Conclusion: LLLT is recommended against the background of standard drug therapy to achieve quick clinical outcome together with a long-lasting prolonged effect.

Leishmania parasites present astonishing adaptative abilities that represent a matter of life or death within disparate environments during the heteroxenous parasite life cycle. From an evolutionary perspective, organisms develop methods of overcoming such challenges. Strategies that extend beyond the genetic diversity have been discussed and include variability between parasite cells during the infections of their hosts. The occurrence of Leishmania subpopulation fluctuations with variable structural genomic contents demonstrates that a single strain might shelter the variability required to overcome inconsistent environments. Such intrastrain variability provides parasites with an extraordinary ability to adapt and thus survive and propagate. However, different perspectives on this evolution have been proposed. Strains or species living in the same environment can cooperate but also compete. These interactions might increase the replication rate of some parasites but cause the loss of more aggressive competitors for others. Adaptive responses to intra- and interspecific competition can evolve as a fixed strategy (replication is adapted to the average genetic complexity of infections) or an optional strategy (replication varies according to the genetic complexity of the current infection). This review highlights the complexity of interspecies and intrastrain interactions among Leishmania parasites as well as the different factors that influence this interplay.

This work presents the results of a comprehensive physico-chemical and biological study of hu-mic substances samples – an extract of humic and fulvic acids. The performed loss on drying test showed a 22 times different dry matter content between EHS and FA. The morphology and dis-tribution of particles in the dry residue of the samples assessed using the methods of optical and digital microscopy demonstrated differences in the qualitative features of the microstructures of their surfaces and granulometries. Shimadzu X-ray fluorescence spectrometry revealed Si (8.1 and 1.7%), P (33.5 and 2.7%), S (4.3 and 59.5%), K (1.35 and 2.5%), Ca (10.9 and 3.2%), Mn (0.27 and 0.06%), Fe (11 and 0.05%), Cu (0.16 and 0.45%), Zn (0.06 and 0.02%) in the dry residues of the EHS and FA samples, respectively. A high intensity of the X-ray fluorescence signal for Fe atoms in the EHS sample was demonstrated. The FT-IR spectra for EHS and FA are characterized by simi-lar vibration frequencies that are characteristic of the chromone derivatives (1-benzopyran-4-one). The UV absorption spectrum is characterized by max = 281 nm for FA. The EHS solution showed a fluorescence maximum at em = 560 nm at ex = 280 nm. Using the DLS method, nanoparticles of 1 nm and 200 nm were detected in EHS and FA diluted solutions, which are likely to condition the biochemical and physical properties of humic acids. Using the Spiro-tox-test method, the absence of the toxic effect of humic acids on the cell model of ciliates Sp. am-bigua was established. When the cell model was incubated in a solution of a toxicant of the fluo-roquinolone group, a decrease in toxicity was demonstrated when diluted with the EHS solu-tion. The results of the study of the antiviral activity of EHS and FA showed that the study ob-jects in the culture of Vero-E6 cells, in doses non-toxic to cells, suppress the reproduction of the SARS-CoV-2 virus both in the study of the virucidal effect and in the study of the antiviral activ-ity according to the therapeutic and prophylactic model scheme of injection. The results obtained suggest that standardized drugs based on humic acids may open up new perspectives in their biomedical application as antiviral drugs.

In addition to nucleic acids, various viral proteins are involved in the assembly of virion. If it is possible to create a biologically active agent that leads to the degradation of one of the key proteins for virus assembly and/or destroys the viral factory, then this agent will effectively cope with virus replication. One of these key proteins for the SARS-CoV-2 virus is the nucleocapsid protein (N-protein). As such a bioactive agent, we offer a modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic to the N-protein, contains an amino acid sequence for the attraction of the Keap1 E3 ubiquitin ligase. This should lead to the subsequent degradation of the N-protein. We have shown that functional properties of modules within the MNT permit its internalization into target cells, endosome escape into the cytosol, and binding to the N-protein. Using flow cytometry and Western blot, it was demonstrated that significant degradation of N-protein is observed when A549 and A431 cells transformed with N-protein are incubated with the developed MNTs. The proposed MNTs open up a new approach for the treatment of viral diseases.

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the rate-limiting step in the ornithine/arginine biosynthesis pathway in eukaryotic and bacterial oxygenic phototrophs. NAGK is the most highly conserved target of the PII signal transduction protein in Cyanobacteria and Archaeplastida (red algae and Chlorophyta). However, yet there is still much to be learnt on how NAGK is regulated in vivo. The use of unicellular green Chlamydomonas reinhardtii as a model system has already been instrumental in identifying several key regulation mechanisms that control nitrogen (N) metabolism. With a combination of molecular-genetic and biochemical approaches, we show the existence of the complex CrNAGK control at transcriptional level, which is dependent on N source and N availability. In growing cells, CrNAGK requires CrPII to properly sense the feedback inhibitor arginine. Moreover, we provided primary evidence that CrPII is only partly responsible for regulating CrNAGK activity to adapt to changing nutritional conditions. Collectively, our results suggest that in vivo CrNAGK is tuned at transcriptional and post-translational levels, and CrPII and additional as yet unknown factor(s) are integral parts of this regulation.

This paper presents the results of an experimental study of the patterns of steel and lead shot transformation under the impact of environmental factors (two types of shot exposed alone and in combination with each other). The analyzed environmental factors include atmospheric precipitation of various acidity and soil solutions with a higher content of organic acids. This research demonstrated that steel shot is characterized by a high transformation rate that is an order of magnitude higher on average than the transformation rate of lead under the same conditions. The prevalence of the suspended iron form (excluding the interaction with organic acids) presents risks for such environmental components as soils and sediments and may be hazardous to the ambient air and natural waters in case of wind erosion and surface runoff from the catchment area. Furthermore, the joint presence of steel and lead shot mutually accelerates the corrosion of both metals, thus increasing the environmental risks.

The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on forebrain and sense organs development. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions.

Background: The nutritional status of women during pregnancy can have a considerable effect on maternal and fetal health, and on perinatal outcome. The aim was to assess the changes occurring in dietary iodine intake, KI supplementation, and smoking habit, and the impact of these changes on the urinary iodine concentration (UIC) during pregnancy in a population of women in Catalonia (Spain). Methods: Between 2009-2011 an observational study including a cohort of women whose pregnancy was monitored in the publically-funded health system in a central region of Catalonia. Women received individual educational counseling imparted, a dietary questionnaire was completed, and a urine sample collected for iodine determination at each trimester visit. Results: 633 (67.9%) women answered the questionnaire at all 3 visits. The percentage of women with a desirable UIC (≥150μg/L) increased from the first to the second trimester and remained stable in the third (p<0.001). Analysis of the relationship between UIC≥150 μg/L and the women’s dietary habits showed that the percentage with UIC≥150 μg/L increased with greater consumption of milk, fresh vegetables, and fruit in the first trimester, and the same was true for iodized salt use in all three trimesters and iodine supplementation in all three. Conclusion: During pregnancy increased intake of milk, iodized salt, and iodine supplements was associated with an increase in the UIC.

Due to low culturing costs and high seed protein contents, legumes represent the main global source of food protein. Pea (Pisum sativum L.) is one of the major economically important legume crops, impacting both animal feed and human nutrition. Therefore, the quality of pea seeds needs to be ensured in the context of sustainable crop production and nutritional efficiency. Obviously, changes in seed protein patterns might directly affect both of these aspects. Thus, here we address the pea seed proteome in more detail and provide, to the best of our knowledge, the most comprehensive annotation of the functions and intracellular localization of pea seed proteins. Accordingly, 1938 and 1989 non-redundant proteins were identified in yellow and green pea seeds, in total. Only 35 and 44 proteins, respectively, could be additionally identified after protamine sulfate precipitation (PSP) potentially indicating the high efficiency of our experimental workflow. In total 981 protein groups could be assigned to 34 functional classes, which were to a large extent differentially represented in yellow and green seeds. Closer analysis of these differences by processing of the data in KEGG and String databases revealed their possible relation to a higher metabolic status and reduced longevity of green seeds.

Despite the recognition of the importance of stakeholder inclusion into decisions about new solutions offered to society, responsible innovation (RI) has stalled at the point of articulating a process of governance with a strongly normative loading, without clear practical guidelines toward implementation practices. The principles of RI direct us to involve the user early in the innovation process. However, it lacks direction of how to involve users and stakeholders into this process. In this article, we try to understand how to empower users to become a part of innovation process though empirical cases. Based on 11 cases of firms innovating in digital health and welfare services, we look on firm practices for user integration into their innovation process, as well as how user’s behavior is changing due to new trends such as availability of information and digitalization of services. We try to explore this question through lenses of responsible innovation in the emerging field of digital healthcare.

Real-time estimation of the parameters characterising infectious disease transmission is important for optimization quarantine interventions during outbreaks. One of the most significant parameters is the effective reproduction number - number of secondary cases produced by a single infection. The current study presents an approach for estimating the effective reproduction number and its application to COVID-19 outbreak. The method is based on fitting SIR epidemic model to observation data in a sliding time window and allows to show real-time dynamics of reproduction number at any phase of epidemic for countries globally. Online data on COVID-19 daily cases of infections, recoveries, deaths are used.Finally, time-dependent reproduction number is explored in connection with dynamics of peoples mobility. The method allows to assess the disease transmission potential and understand the effect of interventions on epidemics spread. It also can be easily adapted to future outbreaks of different pathogens. The tool is available online as Python code from the Github repository.

Treatment of various diseases, in particular cancer, usually needs targeting biologically active molecules at a selected subcellular compartment. We modified our previously developed modular nanotransporters (MNTs) for targeting mitochondria. The new MNTs are capable of binding to the protein predominantly localized on the outer mitochondrial membrane, Keap1. These MNTs possessing antiKeap1 monobody co-localize with mitochondria upon addition to the cells. They efficiently interact with Keap1 both in solution and within living cells. A conjugate of the MNT with a photosensitizer, chlorin e6, demonstrates significantly higher photocytotoxicity than chlorine e6 alone. We assume that MNTs of this kind can improve efficiency of therapeutic photosensitizers and radionuclides emitting short-range particles.

In this work, we tried to emphasize whole transcriptome expression changes in the Wistar rats brainstem two hours after acute stress. Most of the genes were upregulated. We detected massive shift of neuropeptides Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptors Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as Glutamate Grin3b, Grm2 and GABA Gpr156, Acetylcholine Chrm4,Chrne, Adreno- Adra2b receptors expression uprising. Intensive increase in expression of intermediate filaments Krt83/Krt86/Krt80/Krt84/Krt87/Krt4/Krt76 and motor proteins Myo7a, Klc3 was detected. Remarkably, at this time we also observed signs of microglia activation. Both expression of anti-inflammatory cytokines Il13, Ccl24 and proinflammatory cytokin’s receptors Il9r, Il12rb1, Tnfrsf14, Tnfrsf13c, Tnfrsf25, Tnfrsf1b were increased. In the Wnt signaling pathway, we have seen increased expression of ligands-receptors Wnt1, Wnt11, Ror2, and also negative regulators Notum, Sfrp5, Sost. Also we conducted cDNA libraries normalization with duplex specific nuclease and compared results. On the basis of our RNAseq data, we chose reference genes for RT-qPCR best suitable for experiments with acute stress.

Patients with COVID-19 demonstrate higher rates of cardiovascular complications, including thromboses and thromboembolism. One may suppose that the action of SARS-CoV-2 transforms stable atherosclerotic plaques into unstable status. Cardiovascular complications in COVID-19 may be caused by progressive viral alteration the blood vessels, including vasa vasorum. A lethal case of ischemic brain disease caused by cerebral atherosclerosis and exacerbated with a stroke during COVID-19 infection is briefly described. The results of autopsy showed perivascular lymphocytic infiltration and signs of vasa vasorum vasculitis with thrombi of adventitial microvasculature. The data discussed in the article are interpreted in context of the concept giving the important role in atherogenesis to vasa vasorum.

Mechanical damage of plant tissues leads to the activation of methanol production and its release in the atmosphere. The gaseous methanol or vapors emitted by the damaged plant induce resistance in neighboring intact plants to bacterial pathogens but create favorable conditions for the viral infection spread. Among Nicotiana benthamiana methanol-inducible genes (MIGs) most are associated with plant defense and intercellular transport. Here we characterize NbMIG21 that encodes a 209-aa protein (NbMIG21p) which does not share any homology with annotated proteins. NbMIG21p was demonstrated to contain nucleolus localization signals (NoLS). Co-localization studies with fibrillarin and coilin, nucleolus and Cajal bodies marker proteins, revealed that NbMIG21p is distributed between these subnuclear structures. Our results show that recombinant NbMIG21 possess DNA-binding properties . Similar to gaseous methanol effect an increased NbMIG21 expression leads to the downregulation of the nuclear import of NLS-containing proteins as was demonstrated on the model GFP-NLS protein. Moreover, upregulated NbMIG21 facilitates tobacco mosaic virus (TMV) intercellular transport. We identified NbMIG21 promoter (PrMIG21) and showed that it is methanol-sensitive thus induction of NbMIG21 expression occurs at the level of transcription. Our findings suggest that methanol-activated NbMIG21 might participate in creating favorable conditions for the viral reproduction and spread.

Natural Fibre Composites (NFC) are eco-friendly, sustainable alternatives to synthetic polymers. However, some intrinsic natural fillers´ properties hinder their widespread implementation as re-inforcement in polymeric matrices and require further investigation. In the scope of this study, the thermal, rheologic, mechanical (tension and flexural modes), morphological properties, water ab-sorption and dimensional stability of the NF polypropylene (PP) based injection moulded compo-sites with the rice husk (rh) and olive pits (op) of 20 wt% and 30% wt%, were investigated. The results suggest that the higher content of the rice husk and olive pits led to a similar reduction of the Melt Flow Index (MFI), independent of the additive type compared to virgin polypropylene (PPv). The melting and crystallization temperatures of the PPrh and PPop composites did not change with statistical significance. The composites are stiffer than the PP matrix by up to 49% and possess higher mechanical strength in what concerns the tension mode at the expense of de-creased ductility. PPrh and PPop have superior flexural modulus in the bending mode, while the flexural strength improvement was accomplished for the PP30%rh. The dimensional stability of the composites was improved as the linear shrinkage in the flow direction was decreased by 49% for PPrh and 30% for PPop, positively correlating with an increase in the filler content and stiff-ness. PPop was less susceptible to water sorption than PPrh due to fibres' composition and larger surface-to-area volume ratios.

Stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V exhibit properties for bio-medical applications; however their tribocorrosion associated with metallosis is still a major concern. Therefore smoothing DLC coatings aiming for the improvement of tri-bocorrosion and cell viability of stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V with and without DLC coatings were compared. The motivation was due to many papers detailing metallosis caused by metal debris in the body's soft tissues. Nowadays, metallosis is responsible for almost of prosthesis replacement surgeries. DLC coatings were produced using the Plasma Enhanced Chemical Vapor Deposition (PECVD) technique; acetylene gas was used as a carbon precursor, and silane gas produced an amorphous silicon interface between the DLC coating and metal substrate. A combined setup of techniques thoroughly evaluated the coatings considering chemical composition, coatings adhesion at a metallic substrate, scratch resistance, and tribocorrosion susceptibility. The cytotoxicity and genotoxicity of metallic samples with and without DLC coatings were analyzed, considering cell viability and its correlation with coatings’ chemical composition

In this work epitaxial Au islands have been grown on epitaxial α-Fe2O3 thin film by pulsed laser deposition on SrTiO3(111) substrate. Both Au and α-Fe2O3 layer show an island-type growth with an average particle size of 40 and 62 nm, respectively. The crystallographic coupling of lattices is confirmed with a rotation of 30º between the in-plane crystallographic axes of α-Fe2O3(0001) structure and those of SrTiO3(111) substrate and between the in-plane crystallographic axes of Au(111) and those of α-Fe2O3(0001) structure. α-Fe2O3 is the only phase of iron oxide identified before and after its functionalization with Au nanoparticles. In addition, its structural character-istics are also preserved after Au deposition, with minor changes at short-range order. The func-tional character of the complex systems as gas sensor has been proven at room temperature. Con-ductance measurements of Au(111)/α-Fe2O3(0001)/ SrTiO3(111) system show that the incorpora-tion of Au islands on top of the α-Fe2O3(0001) layer induces an enhancement of the gas-sensing ac-tivity for CO and CH4 gas in comparison to a bare α-Fe2O3(0001) layer grown on SrTiO3(111).

The growth of demand for metallic minerals has faced with the need for new techniques and improving technologies for all mine life cycle operations. Nowadays, the exploitation of old tailings and mine wastes facilities could represent a solution to this demand, with economic and environmental advantages. W-Sn Panasqueira Mine has been operating for more than 100 years. Its first processing plant “Rio” was located near Zêrere river being the mineral processing residues deposited on the top hillside on the margin of this river in Cabeço do Pião tailings dam. The lack of maintenance and monitoring of this enormous structure in the last twenty years represents high risks to the environment and population of the surrounding region. The re-mining of the tailings by hydrometallurgical methods was considered, in order to satisfy these two enounced conditions - metals demand and environmental risk, aiming for the sale of the metal to pay the environmental intervention. Field samples campaign allowed collecting data and results from laboratory tests driving to use regression optimization. The re-mining solution was studied, taking into account the technical, economic, social, and environmental aspects.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), 21% septal reduction therapy. Sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3) and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63 and FLNC; thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p=0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; family studies on some rare variants enriched the worldwide knowledge in HCM.

Over the last decade, there has been a growing interest in the use of a wide range of phytoadditives to counteract the harmful effects of heat stress in poultry. Willow (Salix spp.) is a tree with a long history. Among various forms, willow bark is an important natural source of salicin, β-O-glucoside of saligenin, but also of polyphenols (flavonoids and condensed tannins) with antioxidant, antimicrobial and anti-inflammatory activity. In light of this, the current review presents some literature data aiming to: (1) describe the relationship between heat stress and oxidative stress in broilers, (2) present or summarize literature data on the chemical composition of Salix species, (3) summarize the mechanisms of action of willow bark in heat-stressed broilers, (4) present different biological effects of the extract of Salix species in different experimental models.

Current progress in the prediction of mechanical behavior of solids requires understanding of spatiotemporal complexity of plastic flow caused by self-organization of crystal defects. It may be particularly important in hexagonal materials because of their strong anisotropy and combination of different mechanisms of plasticity, such as dislocation glide and twinning. These materials often display complex behavior even on the macroscopic scale of deformation curves, e.g., a peculiar three-stage elastoplastic transition, the origin of which is a matter of debates. The present work is devoted to a multiscale study of plastic flow in α-Ti, based on simultaneous recording of deformation curves, 1D local strain field, and acoustic emission (AE). It is found that the average AE activity also reveals three-stage behavior, but in a qualitatively different way depending on the crystallographic orientation of the sample axis. On the finer scale, the statistical analysis of AE events and local strain rates testifies to an avalanche-like character of dislocation processes, reflected in power-law probability distribution functions. The results are discussed from the viewpoint of collective dislocation dynamics and are confronted to predictions of a recent micromechanical model of Ti strain hardening.

Modern medical needs call for the efficient remedies against bacterial diseases including severe pulmonary infections reported as a secondary SARS-Cov-2 infection. Here, we propose imprinted drug ciprofloxacin (CF) into the polymer based on methyl-β-cyclodextrin (MCD) via template synthesis. The obtained polycarbamide nanoparticles possess CF's sustained drug release. The interaction of human serum albumin (HSA) with CF and CF-MCD carriers was conducted by FRET, FTIR, fluorescence, and circular dichroism spectroscopy. These studies uncovered that MCD decreases CF's binding efficiency by 2 times, whereas CF’s encapsulation in polymer matrix doubles the Ka value. The changes in HSA’s secondary structure indicate no alterations in the main mechanism of complex formation between CF and HSA in the presence of MCD-based carries. The drug delivery system demonstrates prolonged CF release at pH 7.4 in presence of HSA (model conditions of blood plasma). CF-MCD carriers inhibit E. coli and B. subtilis growth, but for MAX systems we observed a MIC’s increase (~2 times). We believe that our findings are important for further development of new efficient drug forms.

Human serum albumin (HSA) is multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. Formulating anticancer drugs with HSA is a clinically validated approach to improve the pharmacological properties and provide targeted delivery (passive and active) of cytotoxic payload to the tumor (such as in Abraxane). A number of receptors facilitating HSA uptake from systemic circulation have been characterized. What is interesting, such uptake may differ depending on the nature and quantity of ligands bound to HSA. Based on this, one might like to modify the HSA in a way that its distribution is more favorable for certain therapeutic purposes, thus ensuring more efficient delivery of the therapeutic cargo to disease site. E.g. Levofloxacin (LV), broad spectrum antibiotic drug, could benefit from extended systemic exposure, and stronger interaction with plasma proteins could be useful for this purpose. We have engrafted monomeric or polymeric CDs on the surface of HSA molecules to strengthen the LV adsorption (CD-LV dissociation constant is three orders of magnitude lower than that for HSA-LF). We have found that (HSA-HPolS)conj+LV exhibited the highest activity against E. coli, whereas (HSA-HPCD)conj+LV was the most effective against B. subtilis; and both HSA conjugates were more potent than LV alone or LV with HSA. Further fine-tuning of HSA could yield an improvement in biodistribution, and thus a more favorable risk/benefit ratio.

Solidago virgaurea L. (European goldenrod, Woundwort), Asteraceae, is a familiar medicinal plant in Europe and other parts of the world, widely used and among the most researched species from its genus. The aerial parts of European goldenrod have long been used for urinary tract conditions and as an anti-inflammatory agent in the traditional medicine of different peoples. Its main chemical constituents are flavonoids (mainly derived from quercetin and kaempferol), C6-C1 and C6-C3 compounds, terpenes (mostly from the essential oil), and a large number of saponin molecules (mainly virgaureasaponins and solidagosaponins). Published research on its potential activities is critically reviewed here: antioxidant, antiinflammatory, analgesic, spasmolitic, antihypertensive, diuretic, antibacterial, antifungal, antiparasite, cytotoxic and antitumor, antimutagenic, antiadipogenic, antidiabetic, cardioprotective, and antisenescence. The evidence concerning its potential benefits is mainly derived from non-clinical studies, some effects are rather modest, whereas others are more promising, but need more confirmation in both non-clinical models and clinical trials.

The addition of prebiotics is one of the most important ways to improve the techno-functional properties of bread. In this study, the effects of resistant starch, polydextrose, and inulin on the wheat flour, dough, and bread properties were investigated. In farinography results, resistant starch significantly increased the development time (2:18) with a boosting effect, but polydextrose (1:48) and inulin (1:36) weakened the dough (P &lt;0.05). Inulin, polydextrose, and resistant starch had the most effect on reducing water absorption (40, 43.2, and 48.9) respectively (P &lt;0.05). According to extensography data, inulin had the best result in baking compared to other polysaccharides. In terms of baked breads, samples containing resistant starch had high moisture that could be due to starch gelatinization and moisture-retaining, which delays the staling process of bread. Inulin, polydextrose, and resistant starch prebiotic ingredients affected dough rheological properties and bread quality, and organoleptic characteristics, however, resistant starch was the best.

This paper presents a study of human blood sera samples, collected in various regions of the Russian Federation, with regard to both vaccine and pandemic avian influenza viral strains. Just before the 2022-2023 epidemic season, herd immunity to seasonal influenza A viruses was reportedly lower than before the COVID-19 pandemic. Since no stable circulation of A/H5Nx and A/H9N2 influenza in the human population was observed during this period, we believe 100% vaccination against seasonal influenza is necessary for employees of poultry farms and other organizations, closely connected to the breeding and processing of poultry. In addition to protection against seasonal influenza, vaccination can hamper the emergence of new viral variants, driven by genome reassortment, during simultaneous infection of humans with seasonal human and animal influenza viruses.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

There is little information about moisture changes in different altitudinal belts in mountainous regions of the Southern Russian Far East. We present ecological-taxonomic composition of the diatom flora, the botanical composition of peat of small mountain lake/mire complexes located in the Central Sikhote-Alin within large landslides on the paleovolcano slopes are identified. Frequent changes in diatom assemblages and peat-forming plants indicate unstable hydroclimatic conditions with varying degrees of watering and dry condition up to complete overgrowth of the lakes. Frequent change of sphagnum mosses with different trophic preferences was established. The chronology is based on 11 radiocarbon dates. Accumulation rates reached up to 1.9 mm/year, the temporal resolution for the reconstructions is up to 30–40 years. The tendencies of lake evolution depended on different-scale hydroclimatic changes for the last 4400 yr. The most detailed data for the last 2600 yr were obtained from the Nizhnee Lake sequence, more sensitive to climatic changes. The main reason for the change in the hydrological regime of the lakes was variations in precipitation during short-term climatic changes. The sediment record moisture fluctuations are relatively well correlated with regional patterns reflecting summer monsoon intensity and cyclogenesis activity.

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low-molecular-weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plant cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, including carotenoids, tocopherol (vitamin E), ubiquinone and plastoquinone. Their functioning and their reactivity with respect to individual ROS are described. The review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow to obtain various plant lines with given properties in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of the biosynthesis and the content of these antioxidants are discussed.