Curative Activity Research Articles

Polymyxin B1 and E2 From Paenibacillus polymyxa Y-1 for Controlling Rice Bacterial Disease.

To discover novel microbial pesticide for controlling rice bacterial disease, polymyxin B1 and E2 were firstly isolated from the supernatant of fermentation broth of Paenibacillus polymyxa Y-1 by bioactivity tracking separation. It is shown that polymyxin B1 and E2 had remarkable in vitro inhibitory activities to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) with the EC50 values of 0.19 μg/ml and 0.21 μg/ml against Xoo, and 0.32 μg/ml and 0.41 μg/ml against Xoc, respectively, which were better than those of Zhongshengmycin (0.31 μg/ml and 0.73 μg/ml) and Bismerthiazol (77.48 μg/ml and 85.30 μg/ml). Polymyxins B1 and E2 had good protection and curative activities against rice bacterial leaf blight (BLB) and rice bacterial leaf streak (BLS) in vivo. The protection and curative activities of polymyxins B1 (45.8 and 35.8%, respectively) and E2 (41.2 and 37.0%, respectively) to BLB were superior to those of Zhongshengmycin (34.8 and 29.8%, respectively) and Bismerthiazol (38.0 and 33.5%, respectively). Meanwhile, the protection and curative activities of polymyxins B1 (44.8 and 39.8%, respectively) and E2 (42.9 and 39.9%, respectively) to BLS were also superior to those of Zhongshengmycin (39.7 and 32.0%, respectively) and Bismerthiazol (41.5 and 34.3%, respectively). Polymyxin B1 exerted the anti-pesticide properties via destroying the cell integrity of Xoo, reducing its infectivity and enhancing rice resistance against pathogens through activating the phenylpropanoid biosynthesis pathway of rice. It is indicated that polymyxin B1 and E2 were potential microbial pesticides for controlling rice bacterial disease.

Targeted photoimmunotherapy for cancer.

Photodynamic therapy (PDT) is a clinically approved procedure that can exert a curative action against malignant cells. The treatment implies the administration of a photoactive molecular species that, upon absorption of visible or near infrared light, sensitizes the formation of reactive oxygen species. These species are cytotoxic and lead to tumor cell death, damage vasculature, and induce inflammation. Clinical investigations demonstrated that PDT is curative and does not compromise other treatment options. One of the major limitations of the original method was the low selectivity of the photoactive compounds for malignant over healthy tissues. The development of conjugates with antibodies has endowed photosensitizing molecules with targeting capability, so that the compounds are delivered with unprecedented precision to the site of action. Given their fluorescence emission capability, these supramolecular species are intrinsically theranostic agents.

In vivo assessment of the antimalarial activity and acute oral toxicity of an ethanolic seed extract of Spondias pinnata (L.f.) Kurz

BackgroundIn response to the persistent problem of malaria resistance, medicinal herbal plants can be used as a source of potential novel antimalarial agents. Therefore, the aim of this study was to evaluate the in vivo antimalarial activity and toxicity of an ethanolic seed extract of Spondias pinnata (L.f.) Kurz (S. pinnata).MethodsQualitative phytochemical screening of the extract was performed using standard procedures, and the constituents were determined by gas chromatography–mass spectrometry (GC–MS). The in vivo antimalarial activity was assessed against the Plasmodium berghei ANKA strain in mice based on 4-day suppressive, curative and prophylactic tests. In addition, the acute toxicity of the extract was evaluated after oral administration of a single dose of 2,000 mg/kg body weight.ResultsPhytochemical screening tests on the ethanolic S. pinnata seed extract revealed the presence of terpenoids, tannins, and coumarins. GC–MS analysis of the extract led to the identification of twenty-nine phytochemical compounds, including oleic acid amide, β-sitosterol, linoleic acid, oleic acid, protocatechuic acid, syringic acid and gallic acid. The results of the 4-day suppressive test revealed that mice treated with 250, 500, 600 and 800 mg/kg doses of the ethanolic S. pinnata seed extract showed significant parasitemia suppression in a dose-dependent manner, with 22.94, 49.01, 60.67 and 66.82% suppression, respectively, compared to that of the negative control group. All the doses of the ethanolic seed extract significantly suppressed parasitemia (P < 0.05) during the curative activity test and prolonged the mean survival time compared to those of the negative control group. However, the ethanolic seed extract displayed lower curative and prophylactic activities than the standard drug artesunate. In addition, the ethanolic seed extract showed no signs of toxicity in mice at a dose of 2,000 mg/kg body weight.ConclusionThe S. pinnata seed extract contains various phytochemical compounds with important medicinal properties. The extract showed a significant suppression of parasitemia in a dose-dependent manner, prolonged the mean survival time and exhibited significant curative and prophylactic activities. The overall results of this study demonstrated that the S. pinnata seed extract possessed promising in vivo antimalarial activity against P. berghei ANKA, with no toxicity. The findings from the present study provide scientific evidence supporting the use of S. pinnata seeds in the development of new drugs for malaria treatment. Additional studies are needed to isolate and identify the active compounds as well as to understand the mechanism of inhibition.

Standardized evidence-based approach for assessment of oncogenic and clinical significance of NTRK fusions

Gene fusions involving the neurotrophic receptor tyrosine kinase genes NTRK1, NTRK2, and NTRK3, are well established oncogenic drivers in a broad range of pediatric and adult tumors. These fusions are also important actionable markers, predicting often dramatic response to FDA approved kinase inhibitors. Accurate interpretation of the clinical significance of NTRK fusions is a high priority for diagnostic laboratories, but remains challenging and time consuming given the rapid pace of new data accumulation, the diversity of fusion partners and tumor types, and heterogeneous and incomplete information in variant databases and knowledgebases. The ClinGen NTRK Fusions Somatic Cancer Variant Curation Expert Panel (SC-VCEP) was formed to systematically address these challenges and create an expert-curated resource to support clinicians, researchers, patients and their families in making accurate interpretations and informed treatment decisions for NTRK fusion-driven tumors. We describe a system for NTRK fusion interpretation (including compilation of key elements and annotations) developed by the NTRK fusions SC-VCEP. We illustrate this stepwise process on examples of LMNA::NTRK1 and KANK1::NTRK2 fusions. Finally, we provide detailed analysis of current representation of NTRK fusions in public fusion databases and the CIViC knowledgebase, performed by the NTRK fusions SC-VCEP to determine existing gaps and prioritize future curation activities.

Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach

Liver inflammation is associated with an increased risk of liver fibrosis that substantially progresses to cirrhosis. Recently, usage of the herbal supplement has been increased because of its emerging role to dominate oxidative stress in hepatic injury. Orientin is one of the bioactive flavonoids that possesses a diversity of curative activities. Therefore, the present study was conducted to evaluate the anti-inflammatory role of orientin (1 mg/kg) in vitro in lipopolysaccharide (LPS)-induced inflammation in hepatic stellate cells (HSCs) and in vivo in carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Moreover, the current study was supported by in silico investigation. Orientin demonstrated protection against LPS-induced HSC inflammation as evidenced by a decrease in iNOS, NO, and TNF-α and inhibition of the fibrotic markers ZEB-2 and PTEN. In addition, orientin afforded protection against CCl4-induced liver fibrosis in mice as shown from decreased AST/ALT ratio, inhibition of the pro-inflammatory mediators TNF-α, IL-6, IL-8, and IFN-γ, reduction of fibrotic markers ZEB-2 and PTEN, and improvement of the histopathological changes. Furthermore, the docking study demonstrated virtual interactions of orientin with ZEB-2 and PTEN. Taken together, the current study suggested that the protective effects of orientin against LPS- and CCl4-induced liver inflammation are via inhibition of fibrotic markers and reduction of pro-inflammatory mediators.

Postharvest sour rot control in lemon fruit by natamycin and an Allium extract

Citrus sour rot caused by Geotrichum citri-aurantii is one of the most important postharvest diseases in citrus fruit, causing huge economic losses. Traditionally, it has been controlled by the postharvest application of guazatine and propiconazole fungicides, but restrictions in their use make it urgent to find an alternative for sour rot management. Natamycin, a common food preservative, and the organosulfuric compounds extracted from Allium species are safe food additives that control different foodborne pathogens. In the present study, the curative activities of commercial formulations of natamycin (Fruitgard Nat 20) and an Allium extract (PTSO: propyl thiosulfinate oxide; Proallium FRD®), were evaluated for the control of G. citri-aurantii in artificially inoculated lemon fruit. Trials in laboratory and in commercial conditions were carried out to explore the feasibility of including both compounds as part of a safe postharvest sour rot disease control strategy. Under controlled laboratory conditions, sour rot was significatively reduced by 500 mg L−1 of natamycin, 580 mL L−1 of PTSO and 290 mL L−1 of PTSO + 4% of a food coat, applied by immersion. Nevertheless, the maximum dose of PTSO (580 mL L−1) caused phytotoxicity on the fruit rind. In commercial drenching conditions, 290 mL L−1 of PTSO + 4% of a food coat reduced sour rot incidence similar to conventional treatment. In a packing line treatment, spray application of 500 mg L−1 of natamycin with a previous dip in sodium bicarbonate, resulted in nearly 70% reduction of disease incidence compared to conventional salt application. A second commercial experiment revealed that fruit drenching with 290 mL L−1 of PTSO + 4% food coat followed by an in-line cascade application of 500 mg L−1 of natamycin is completely effective for sour rot control after 20 days at 5 °C. Further exposure at room temperature for 7 d showed a 61% reduction in sour rot incidence compared to the control. Results revealed that natamycin and PTSO are promising tools for sour rot control used alone or combined as part of an integrated postharvest strategy.

Antiviral Activities of Novel Myricetin Derivatives Containing 1,3,4-Oxadiazole Bisthioether.

A class of novel myricetin derivatives containing 1,3,4-oxadiazole bisthioether were synthesized. The results of antiviral biological activity demonstrated that the partially compounds exhibited good antiviral effects against tobacco mosaic virus. The in vivo curative and protective activities of compound E12 against TMV was quite significant. The EC50 value of the curative activity of E12 was 128.8 μg/mL, while the value of ningnanmycin was 296.4 μg/mL. Similarly, the EC50 value of the protective activity of E12 was 99.1 μg/mL, while the value of ningnanmycin was 307.6 μg/mL. The microscale thermophoresis data indicated that the binding value of ningnanmycin and TMV-CP was 2.726±1.301 μM, which was not as good as the binding value of E12 and TMV-CP was 0.029±0.013 μM. This study showed that novel myricetin derivatives containing 1,3,4-oxadiazole bisthioether may be a kind of agricultural antiviral drugs with great potential.

1,3,4-Oxadiazole Contained Sesquiterpene Derivatives: Synthesis and Microbiocidal Activity for Plant Disease.

A series of 1,3,4-oxadiazole contained sesquiterpene derivatives were synthesized, and the activity of the target compounds against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and tobacco mosaic virus (TMV) were evaluated. The biological activity results showed that the EC50 values of compounds H4, H8, H11, H12, H14, H16, and H19 for Xac inhibitory activity were 33.3, 42.7, 56.1, 74.5, 37.8, 43.8, and 38.4 μg/ml, respectively. Compounds H4, H8, H15, H19, H22, and H23 had inhibitory effects on Xoo, with EC50 values of 51.0, 43.3, 43.4, 50.5, 74.6, and 51.4 μg/ml, respectively. In particular, the curative and protective activities of compound H8 against Xoo in vivo were 51.9 and 49.3%, respectively. In addition, the EC50 values of the inactivation activity of compounds H4, H5, H9, H10, and H16 against TMV were 69.6, 58.9, 69.4, 43.9, and 60.5 μg/ml, respectively. The results of molecular docking indicated that compound H10 exhibited a strong affinity for TMV-coat protein, with a binding energy of −8.88 kcal/mol. It may inhibit the self-assembly and replication of TMV particles and have an anti-TMV effect, which supports its potential usefulness as an antiviral agent.

Antifungal activity of l-azetidine-2-carboxylic acid isolated from Disporopsis aspera rhizomes against Podosphaera xanthii.

Powdery mildew is one of the fungal diseases commonly occurring in the process of cucurbits protected and open cultivation. Cucumbers, melons and pumpkins are extremely susceptible. The secondary metabolites produced by plants are important sources of fungicides with low toxicity and environment-friendly characteristics. The aim of this study was to reveal the main active ingredient in the crude extracts of Disporopsis aspera rhizomes that inhibit cucurbits powdery mildew and evaluate its activities. In this study, the crude extracts of Disporopsis aspera rhizomes were found to exhibit excellent antifungal activity aganist Podosphaera xanthii, a causal agent of cucurbits powdery mildew. Based on the bioassay-guided method, l-azetidine-2-carboxylic acid (l-Aze) was isolated from this genus for the first time. l-Aze showed unique curative and eradicative activity against Podosphaera xanthii in vivo, which has never been reported before. Microscopic observation revealed that the curative spraying of l-Aze could effectively inhibit the mycelial growth, resulting in hollow parts of the mycelia, not forming conidiophores, and interrupting the life cycle of powdery mildew. The eradicative spraying of l-Aze caused the fracture of mycelia and deformity of conidiophores, which could not continue to produce conidia. l-Aze was the main active ingredient of D. aspera against Podosphaera xanthii, which had both curative and eradicative effects. The results provided a strong possibility of using the crude extracts of D. aspera rhizomes and its main effective component, l-Aze as biocontrol agents to control cucurbits powdery mildew.

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments.

Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC50 value of that was 2.9 μg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC50 = 12.5 μg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 μg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.

Ferulic acid derivatives with piperazine moiety as potential antiviral agents.

Plant virus diseases are difficult to control and severely threaten the productivity of crops, which leads to huge financial losses. To discover the new antiviral drugs, 34 novel ferulic acid derivatives with piperazine moiety were synthesized, and the antiviral activities were systematically screened as well. Bioassay results indicated that most of the target compounds had outstanding antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. In particular, compound E2 exhibited remarkable curative activities to TMV and CMV with EC50 values of 189.0 and 401.7μg/mL compared to those for ningnanmycin (387.0, 519.3μg/mL) and ribavirin (542.1, 721.5μg/mL). And then the mechanisms of compound E2 were studied by chlorophyll content, differentially expressed proteins and genes tests. The excellent antiviral activity of compound E2 was closely associated with the increase in host photosynthesis, which was confirmed by chlorophyll content, differentially expressed proteins and genes assays. Compound E2 can be considered as a lead structure for the discovery of new antiviral agents. © 2022 Society of Chemical Industry.

Tanggung Jawab Yang Lahir Dari Kewajiban Atas Kesehatan Masyarakat Di Masa Pandemi Covid-19 Dalam Perspektif HAM (Hak Asasi Manusia)

Covid-19 is a crucial health issue, as a right that must be fulfilled because it is one of human rights and the state has responsibility for public health in the form of promotive, preventive, curative and rehabilitative activities, especially in the era of covid 19. knowing the position of public health as part of human rights and the responsibility of the State for the fulfillment of health during the Covid-19 period based on the perspective of Law Number 39 of 1999 concerning Human Rights jo. Health Law Number 36 Year 2009 concerning Health. This research is a normative juridical research, with a statutory approach and a conceptual approach using legal materials in the form of legislation and some relevant literature. The technique of collecting legal materials is carried out by literature study activities using legal materials analysis techniques in the form of grammatical, systematic, and teleological. Interpretations.

Design, synthesis, and bioassay of novel 1‐(3‐chloropyridin‐2‐yl)‐5‐amino‐4‐pyrazole derivatives containing a 1,3,4‐thiadiazole thioether or sulfone moiety

AbstractA series of novel 1‐(3‐chloropyridin‐2‐yl)‐5‐amino‐4‐pyrazole derivatives containing a 1,3,4‐thiadiazole thioether or sulfone moiety were designed and synthesized. All the title compounds were confirmed by 1H NMR, 13C NMR, and MS, and the intermediate 2 and title compound 5e were confirmed by single crystal X‐ray diffraction analysis. Bioassay evaluation revealed that compound 5a (54.2 ± 2.0%) and 5r (75.2 ± 3.9%) exhibited good curative and protection activity against TMV, respectively, which was slightly lower than that of ningnanmycin (57.1 ± 2.2% and 73.8 ± 3.4%). Compound 5b (64.7 ± 8.5% and 67.7 ± 2.1%) exhibited good curative and protective activity against CMV, which was better than that of ningnanmycin (55.8 ± 1.4% and 64.2 ± 5.8%). The lethality rates of 5a, 5c, 5d, 5h, 5j, 5n, 5o, 5p, 5q, 5r, 5t, 6a, and 6e against C. pipiens were 100% at a concentration of 10 μg/ml, as well as chlorantraniliprole (100%). These results may provide enough support to justify further molecular design and derivation.

A Comparison of Basti Instruments Used in Samhita and Current Period with special reference to Mode of Action

Basti is one among the Pancha Karma procedures which has a multifaceted action. Basti is considered to be the best therapy, also known as “Ardha Chikitsa” as well as “Poorna Chikitsa” because it is not only having curative action, but also preventive and promotive actions. Basti is a complex, but systematic procedure having wide therapeutic potency. Basti Sammelana is a unique series of steps which also contributes to the mode of action of Basti. This process is especially told for Nirooha type of Basti, where there is a combination of drugs present. Different Acharyas has given a wide set of instruments in Basti Sammelana, but in the current scenario modifications has been done with the advanced technology. In administration of Basti karma, owing to the practicality time to time changes has been incorporated. Here, an effort has made to compile and critically analyse the different instruments used in the Basti Sammelana and administration of Basti.

Determination of fenamidone residues by surface-enhanced Raman spectroscopy

The purpose of this study is to establish a novel, simple and rapid surface-enhanced Raman spectroscopy (SERS) detection technology for fenamidone. Fenamidone is a fungicide widely used with curative activity against oomycete diseases. Gold nanoparticles (AuNPs) were prepared by improved trisodium citrate reduction method of chloroauric acid. As a surface-enhanced Raman scattering (SERS) active colloid, the optimized product had the advantages of high sensitivity, reproducibility and chemical stability. The Results showed that the detection limit of fenamidone adsorbed on AuNPs was 0.01 mg/kg. The linear response between SERS intensity and logarithmic concentration was R2 = 0.9562. The method was preliminary applied in tobacco sample and showed its potential to serve as an alternative rapid quantification method of fenamidone residues with simplicity, efficiency, high accuracy and precision.

Evaluation of the Potency and Safety of Model Clinic Polyherbal Anti-Malaria Tea

Background: The Model Clinic Antimalaria Tea (AMT) is a product of the Herbal Clinic unit, Department of Pharmacognosy, University of Lagos. Its ingredients are the dried and powdered leaves of Mangifera indica, Psidium guajava, Carica papaya and Cymbopogon citratus. Objective: The objective of this study is to evaluate the potency and safety of AMT. Materials and methods: AMT was assessed for antimalarial activity against chloroquine- sensitive Plasmodium bergheii NK65 – infected mice using the suppressive and the curative test procedures at its half, full and double the prescribed dose (3.45, 6.90, and 13.80 mg kg-1 respectively). Chloroquine 5 mg kg-1 (CQ) was used as positive control while water was the normal control. The test parameters were parasitaemia, weight, PCV and temperature. AMT safety was assessed by acute toxicity test and microbial limit (using the pour plate method) and heavy metals limit test (using spectrophotometry). Results: All the treated groups, except water, showed curative and suppressive antimalarial activity in the following order: CQ &gt; AMT 13.80 mg kg-1 &gt; AMT 6.90 mg kg-1 &gt; 3.45 mg kg-1 which is dose-dependent. Oral administration of AMT at a dose of 4,000 mg kg-1 produced no noticeable deleterious effect. The microbial load and heavy metals content were within passable official limits. Arsenic and Mercury were not detected while Copper, Lead and Zinc occurred in 0.576 ppm, 0.108 ppm and 0.673 ppm respectively. Conclusion: AMT has been shown to exhibit potent and dose-dependent anti-malarial activity against P. bergheii and it is also safe for consumption.

Efficacy of essential oils in the management of soft rot caused by Pectobacterium aroidearum in lettuce

Lettuce is susceptible to several diseases, especially soft rot caused by bacteria of the genus Pectobacterium. Due to the adaptability of this pathogen and the lack of disease control registered for the crop, the objective of this work was to evaluate the effects of essential oils in the management of soft rot caused by P. aroidearum in lettuce. The study was developed at the Universidade do Estado da Bahia, Juazeiro, BA, Brazil, and the essential oils (EOs) of orange, bergamot, lemongrass, palmarosa, citronella, cloves, tea tree, rosemary, sage, and ginger were used in concentrations of 0.25; 0.5; 0.75 and 1.0% to assess the in vitro growth inhibition of the bacterium. Subsequently, the curative effects of the disease were evaluated by applying the EOs that obtained the best results in vitro in lettuce plants of the susceptible variety “Mônica”. The treatments were applied, via spraying, 12 hours after inoculation using the bite method with bacterial suspension. The best in vivo treatment was selected to assess its preventive and curative activity, as well as to find the ideal concentration for reducing epidemiological variables and chromatographic characterization. The EOs of palmarosa, sage, citronella, lemongrass, and cloves (0.25%), and that of sage (0.75%), inhibited bacterial growth in vitro. The EO of salvia showed the best results in vivo, inhibiting the growth of the disease in concentrations of 0.50 and 0.75%, so it was selected for the preventive and curative control tests alone. The preventive treatment was not efficient for the management of soft rot in lettuce, however, from the regression analysis, a concentration of 0.64% of the salvia EO was found as a potential for curative control of this bacteriosis, as it reduces the incidence and severity of the disease. Linalyl acetate and linalool were found in higher concentrations in the chromatographic analysis. These components, probably, conferred the bactericidal capacity of the EO of sage, being potential for the use in the control of P. aroidearum in lettuce.

Trifluoromethylpyridine thiourea derivatives: design, synthesis and inhibition of the self-assembly of tobacco mosaic virus particles.

Devastating plant virus diseases leading to bad harvests and lower quality of crops have made feeding the beyond seven billion population a huge challenge. Nevertheless, growing resistance and cross resistance of crop protection agents have made this challenge harder. Therefore, an efficient crop protection agent with novel structure and mode of action showing higher efficiency and eco-friendly is urgently needed. The coat protein (CP) of a virus is a potential target for the discovery of new antiviral agents. Antiviral molecules can inhibit infection by obstructing the assembly of virus particles. A series of novel phthalamide-like thiourea derivatives containing trifluoromethylpyridine was designed and synthesized. Most of the compounds exhibited good antiviral activity against tobacco mosaic virus (TMV). Compound 7b showed notable curative, protective and inactivation activities against TMV. Its inactivation half-maximal effective concentration (EC50 ) value (20.5μg mL-1 ) was better even than commercial ningnanmycin (23.2μg mL-1 ). Compound 7b also had stronger TMV-CP binding ability than ningnanmycin and destroyed the external shape of TMV particles and hindered the self-assembly of TMV-CP and TMV-RNA. These phthalamide-like thiourea derivatives especially compound 7b containing trifluoromethylpyridine are potential lead compounds and inhibitors of TMV particle self-assembly. © 2021 Society of Chemical Industry.

The Importance of Risk Factors, Methods of Their Calculation and Evaluation, Prognosis in Medicine (Literature Review; Examples of Their Use in Own Clinical Practice) – Second Notice

Introduction. Despite the latest advances in modern medicine, the direct etiological factors of many diseases remain unknown or it is impossible to determine the significance of each of them in their occurrence, so the theory of risk factors is extremely relevant for both theoretical and practical medicine. There are also often situations in which it is necessary to determine the optimal tactics of patient care, because preventive, curative and rehabilitation activities of the doctor require timely prediction of the occurrence probability, further course of the pathological process, its complications, recurrences under the influence of certain environmental factors, threatening and terminal stages, side effects of drugs. Therefore, the need for a practical solution to these problems has become the basis for the theory of risk factors and prognosis methods. The aim of the study. Describe the importance of risk factors and methods of their calculation and evaluation, prognosis in medicine, using literature sources, provide specific examples of their use in own clinical practice. Materials and methods. Content analysis, method of system and comparative analysis, bibliosemantic method of studying the current scientific researches concerning studying of the importance of risk factors and a technique of their calculation and estimation, prognosis in medicine were used. Sources were searched in scientometric databases: PubMed, Medline, Springer, Google Scholar, Research Gate by keywords: risk factors, one-way analysis, multi-factor analysis. 54 literary sources in English and Ukrainian, which highlight the importance of risk factors and methods of their calculation and evaluation, prognosis in medicine were selected and analyzed, we describe the results of their use in our own clinical practice. Results. The concept of risk, as the probability of an adverse event or outcome, is most often used in analytical studies, which are planned to identify the causes and their prevalence of certain conditions. "Risk" cannot be measured directly by the results of information evaluation in one person, but is calculated on the basis of selective observation of a group of persons who are under the influence (exposed group) of a certain factor. Risk factors are potentially pathogenic factors, in contact with which a person may develop a disease. A full analysis of pathological processes, assessment of risk factors and actual risks are impossible without prognosis, as well as multivariate analysis, which is often based on the probabilistic method of A. Wald or the survival curves construction. In practical health care, cases of medical and social research and in clinical studies, it is often necessary to identify the trends (predict) in changes of a certain condition. Conclusions. Determining the risk factors, calculating the actual risks and prognosis play an important role in medicine, because in the doctor's practice there are daily situations that need to determine the optimal tactics taking into account trends, course, severity and results of treatment, therefore, their definition/calculation must be clear and understandable. Depending on the case, the doctor can use the analysis of the score for certain factors, create risk groups, develop a monitoring plan etc. As a result, it becomes possible to create a plan of preventive measures and timely correction of treatment. Keywords: risk, relative risk, absolute risk, chance, forecast.

Sex-related deposition and metabolism of vanisulfane, a novel vanillin-derived pesticide, in rats and its hepatotoxic and gonadal effects

A series of vanillin derivatives have recently been synthesized as effective candidate antiviral agents, with vanisulfane exhibiting pronounced curative and protective activities against cucumber mosaic virus and potato virus Y. However, research on some new pesticides usually ignores their various metabolites and sex-related toxicity. Assisted by 14C labeling, a trial was conducted to investigate the tissue distribution, excretion, and metabolism of vanisulfane in male and female rats for the first time. The results showed that 83.30–87.51% of applied 14C activity was excreted in urine and feces within 24 h of oral administration, and 14C was most abundant in the liver and kidney in both sexes. Interestingly, sex differences were observed in the experiment, with lower body clearance in males than in females 24 h after treatment and preferences for biliary and renal excretion of the pesticide in male and female rats, respectively. A high degradation rate was found for vanisulfane in the plasma; thus, the metabolites of vanisulfane were investigated using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) combined with 14C labeling. One glucuronic acid conjugate and two oxidation metabolites were detected, supporting the monitoring of vanisulfane in vivo. Additionally, rats exposed to vanisulfane exhibited hepatic steatosis in both sexes, along with mild gonadal effects in males. This research offers an effective method for conducting environmental behavioral research and provides new insights for evaluating the potential risks of novel pesticides in mammals from a sex perspective.