Search results for: liver X receptor

Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

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Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

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Authors: Jean Paul Muambangu Milambo, Peter Nyasulu, John Akudugu, Leonidas Ndayisaba, Joyce Tsoka-Gwegweni, Lebwaze Massamba Bienvenu, Mitshindo Mwambangu Chiro

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In 2018, non-communicable diseases (NCDs) were responsible for 48% of deaths in the Democratic Republic of Congo (DRC), with cancer contributing to 5% of these deaths. There is a notable absence of cancer registries, capacity-building activities, budgets, and treatment roadmaps in the DRC. Current cancer estimates are primarily based on mathematical modeling with limited data from neighboring countries. This study aimed to assess cancer subtype prevalence in Kinshasa hospitals and compare these findings with WHO model estimates. Methods: A retrospective observational study was conducted from 2018 to 2020 at HJ Hospitals in Kinshasa. Data were collected using American Cancer Society (ACS) questionnaires and physician logs. Descriptive analysis was performed using STATA version 16 to estimate cancer burden and provide evidence-based recommendations. Results: The results from the chart review at HJ Hospitals in Kinshasa (2018-2020) indicate that out of 6,852 samples, approximately 11.16% were diagnosed with cancer. The distribution of cancer subtypes in this cohort was as follows: breast cancer (33.6%), prostate cancer (21.8%), colorectal cancer (9.6%), lymphoma (4.6%), and cervical cancer (4.4%). These figures are based on histopathological confirmation at the facility and may not fully represent the broader population due to potential selection biases related to geographic and financial accessibility to the hospital. In contrast, the World Health Organization (WHO) model estimates for cancer prevalence in the DRC show different proportions. According to WHO data, the distribution of cancer types is as follows: cervical cancer (15.9%), prostate cancer (15.3%), breast cancer (14.9%), liver cancer (6.8%), colorectal cancer (5.9%), and other cancers (41.2%) (WHO, 2020). Conclusion: The data indicate a rising cancer prevalence in DRC but highlight significant gaps in clinical, biomedical, and genetic cancer data. The establishment of a population-based cancer registry (PBCR) and a defined cancer management pathway is crucial. The current estimates are limited due to data scarcity and inconsistencies in clinical practices. There is an urgent need for multidisciplinary cancer management, integration of palliative care, and improvement in care quality based on evidence-based measures.

Keywords: cancer, risk factors, DRC, gene-environment interactions, survivors

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Authors: Parvesh Singh, Vipan Kumar, Vishu Mehra

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Quinoline-4-ones represent an important class of heterocyclic scaffolds that have attracted significant interest due to their various biological and pharmacological activities. This heterocyclic unit also constitutes an integral component in drugs used for the treatment of neurodegenerative diseases, sleep disorders and in antibiotics viz. norfloxacin and ciprofloxacin. The synthetic accessibility and possibility of fictionalization at varied positions in quinoline-4-ones exemplifies an elegant platform for the designing of combinatorial libraries of functionally enriched scaffolds with a range of pharmacological profles. They are also considered to be attractive precursors for the synthesis of medicinally imperative molecules such as non-steroidal androgen receptor antagonists, antimalarial drug Chloroquine and martinellines with antibacterial activity. 2-Aryl-2,3-dihydroquinolin-4(1H)-ones are present in many natural and non-natural compounds and are considered to be the aza-analogs of favanones. The β-lactam class of antibiotics is generally recognized to be a cornerstone of human health care due to the unparalleled clinical efficacy and safety of this type of antibacterial compound. In addition to their biological relevance as potential antibiotics, β-lactams have also acquired a prominent place in organic chemistry as synthons and provide highly efficient routes to a variety of non-protein amino acids, such as oligopeptides, peptidomimetics, nitrogen-heterocycles, as well as biologically active natural and unnatural products of medicinal interest such as indolizidine alkaloids, paclitaxel, docetaxel, taxoids, cyptophycins, lankacidins, etc. A straight forward route toward the synthesis of quinoline-4-ones via the triflic acid assisted Fries rearrangement of N-aryl-βlactams has been reported by Tepe and co-workers. The ring expansion observed in this case was solely attributed to the inherent ring strain in β-lactam ring because -lactam failed to undergo rearrangement under reaction conditions. Theabovementioned protocol has been recently extended by our group for the synthesis of benzo[b]-azocinon-6-ones via a tandem Michael addition–Fries rearrangement of sorbyl anilides as well as for the single-pot synthesis of 2-aryl-quinolin-4(3H)-ones through the Fries rearrangement of 3-dienyl-βlactams. In continuation with our synthetic endeavours with the β-lactam ring and in view of the lack of convenient approaches for the synthesis of C-3 functionalized quinolin-4(1H)-ones, the present work describes the single-pot synthesis of C-3 functionalized quinolin-4(1H)-ones via the trific acid promoted Fries rearrangement of C-3 vinyl/isopropenyl substituted β-lactams. In addition, DFT calculations and MD simulations were performed to investigate the stability profles of synthetic compounds.

Keywords: dihydroquinoline, fries rearrangement, azetidin-2-ones, quinoline-4-ones

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Authors: Nabiyeva Jamala

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We divide water into drinking, mineral, industrial, technical and thermal-energetic types according to its use and purpose. Drinking water must comply with sanitary requirements and norms according to organoleptic devices and physical and chemical properties. Mineral water - must comply with the norms due to some components having therapeutic properties. Industrial water must fulfill its normative requirements by being used in the industrial field. Technical water should be suitable for use in the field of agriculture, household, and irrigation, and the normative requirements should be met. Heat-energy water is used in the national economy, and it consists of thermal and energy water. Water is a filter-accumulator of all types of pollutants entering the environment. This is explained by the fact that it has the property of dissolving compounds of mineral and gaseous water and regular water circulation. Environmentally clean, pure, non-toxic water is vital for the normal life activity of humans, animals and other living beings. Chemical pollutants enter water basins mainly with wastewater from non-ferrous and ferrous metallurgy, oil, gas, chemical, stone, coal, pulp and paper and forest materials processing industries and make them unusable. Wastewater from the chemical, electric power, woodworking and machine-building industries plays a huge role in the pollution of water sources. Chlorine compounds, phenols, and chloride-containing substances have a strong lethal-toxic effect on organisms when mixed with water. Heavy metals - lead, cadmium, mercury, nickel, copper, selenium, chromium, tin, etc. water mixed with ingredients cause poisoning in humans, animals and other living beings. Thus, the mixing of selenium with water causes liver diseases in people, the mixing of mercury with the nervous system, and the mixing of cadmium with kidney diseases. Pollution of the World's ocean waters and other water basins with oil and oil products is one of the most dangerous environmental problems facing humanity today. So, mixing even the smallest amount of oil and its products in drinking water gives it a bad, unpleasant smell. Mixing one ton of oil with water creates a special layer that covers the water surface in an area of 2.6 km2. As a result, the flood of light, photosynthesis and oxygen supply of water is getting weak and there is a great danger to the lives of living beings.

Keywords: chemical pollutants, wastewater, SSAM, polyacrylamide

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Ei Ei Hlaing, Narissara Lailerd, Sittiruk Roytrakul, Pichapat Piamrojanaphat

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Type 2 diabetes is one of the most common metabolic diseases all over the world. The pathogenesis of type 2 diabetes is not the only dysfunction of pancreatic beta cells but also insulin resistance in muscle, liver and adipose tissue. High levels of circulating free fatty acids, an increased lipid content of muscle cells, impaired insulin-mediated glucose uptake and diminished mitochondrial functioning are pathophysiological hallmarks of diabetic skeletal muscles. Purple rice (Oryza sativa L. indica) has been shown to have antidiabetic effects. However, the underlying mechanism(s) of antidiabetic activity of purple rice is still unraveled. In this research, to explore in-depth cellular mechanism(s), proteomic profile of purple rice supplemented type 2 diabetic rats’ skeletal muscle were analyzed contract with non-supplemented rats. Diabetic rats were induced high-fat diet combined with streptozotocin injection. By using one- dimensional gel electrophoresis (1-DE) and LC-MS/MS quantitative proteomic method, we analyzed proteomic profiles in skeletal muscle of normal rats, normal rats with purple rice supplementation, type 2 diabetic rats, and type 2 diabetic rats with purple rice supplementation. Total 2676 polypeptide expressions were identified. Among them, 24 peptides were only expressed in type 2 diabetic rats, and 24 peptides were unique peptides in type 2 diabetic rats with purple rice supplementation. Acetyl CoA carboxylase 1 (ACACA) found as unique protein in type 2 diabetic rats which is the major enzyme in lipid synthesis and metabolism. Interestingly, DNA damage response protein, heterogeneous nuclear ribonucleoprotein K [Mus musculus] (Hnrnpk), was upregulated in type 2 diabetic rats’ skeletal muscle. Meanwhile, unique proteins of type 2 diabetic rats with purple rice supplementation (bone morphogenetic 7 protein preproprotein, BMP7; and forkhead box protein NX4, Foxn4) involved with muscle cells growth through the regulation of TGF-β/Smad signaling network. Moreover, BMP7 may effect on insulin signaling through the downstream signaling of protein kinase B (Akt) which acts in protein synthesis, glucose uptake, and glycogen synthesis. In conclusion, our study supports that type 2 diabetes impairs muscular lipid metabolism. In addition, purple rice might recover the muscle cells growth and insulin signaling.

Keywords: proteomics, purple rice bran, skeletal muscle, type 2 diabetic rats

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Authors: Sylwia Krawiec, Joanna Cabaj, Karol Malecha

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Nowadays, progress in the field of the analytical methods is of great interest for reliable biological research and medical diagnostics. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements. Chemical sensors have displaced the conventional analytical methods - sensors combine precision, sensitivity, fast response and the possibility of continuous-monitoring. Biosensor is a chemical sensor, which except of conventer also possess a biologically active material, which is the basis for the detection of specific chemicals in the sample. Each biosensor device mainly consists of two elements: a sensitive element, where is recognition of receptor-analyte, and a transducer element which receives the signal and converts it into a measurable signal. Through these two elements biosensors can be divided in two categories: due to the recognition element (e.g immunosensor) and due to the transducer (e.g optical sensor). Working of optical sensor is based on measurements of quantitative changes of parameters characterizing light radiation. The most often analyzed parameters include: amplitude (intensity), frequency or polarization. Changes in the optical properties one of the compound which reacts with biological material coated on the sensor is analyzed by a direct method, in an indirect method indicators are used, which changes the optical properties due to the transformation of the testing species. The most commonly used dyes in this method are: small molecules with an aromatic ring, like rhodamine, fluorescent proteins, for example green fluorescent protein (GFP), or nanoparticles such as quantum dots (QDs). Quantum dots have, in comparison with organic dyes, much better photoluminescent properties, better bioavailability and chemical inertness. These are semiconductor nanocrystals size of 2-10 nm. This very limited number of atoms and the ‘nano’-size gives QDs these highly fluorescent properties. Rapid and sensitive detection of dopamine is extremely important in modern medicine. Dopamine is very important neurotransmitter, which mainly occurs in the brain and central nervous system of mammals. Dopamine is responsible for the transmission information of moving through the nervous system and plays an important role in processes of learning or memory. Detection of dopamine is significant for diseases associated with the central nervous system such as Parkinson or schizophrenia. In developed optical biosensor for detection of dopamine, are used graphene quantum dots (GQDs). In such sensor dopamine molecules coats the GQD surface - in result occurs quenching of fluorescence due to Resonance Energy Transfer (FRET). Changes in fluorescence correspond to specific concentrations of the neurotransmitter in tested sample, so it is possible to accurately determine the concentration of dopamine in the sample.

Keywords: biosensor, dopamine, fluorescence, quantum dots

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Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

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Authors: Ashraf Samir Hakim, Randa Mohamed Alarousy

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The consumption of food contaminated with molds (microscopic filamentous fungi) and their toxic metabolites results in the development of food-borne mycotoxicosis. The spores of molds are ubiquitously spread in the environment and can be detected everywhere. Ochratoxin A is a potentially carcinogenic fungal toxin found in a variety of food commodities , not only is considered the most abundant and hence the most commonly detected member but also is the most toxic one.Ochratoxin A is the most abundant and hence the most commonly detected member, but is also the most toxic of the three. A very limited research works concerning foods of porcine origin in Egypt were obtained in spite of presence a considerable swine population and consumers. In this study, the quality of various ready-to-eat local and imported pork meat and meat byproducts sold in Egyptian markets as well as edible organs as liver and kidney were assessed for the presence of various molds and their toxins as a raw material. Mycological analysis was conducted on (n=110) samples which included pig livers n=10 and kidneys n=10 from the Basateen slaughter house; local n=70 and 20 imported processed pork meat byproducts.The isolates were identified using traditional mycological and biochemical tests while, Ochratoxin A levels were quantitatively analyzed using the high performance liquid. Results of conventional mycological tests for detecting the presence of fungal growth (yeasts or molds) were negative, while the results of mycotoxins concentrations were be greatly above the permiceable limits or "tolerable weekly intake" (TWI) of ochratoxin A established by EFSA in 2006 in local pork and pork byproducts while the imported samples showed a very slightly increasing.Since ochratoxin A is stable and generally resistant to heat and processing, control of ochratoxin A contamination lies in the control of the growth of the toxin-producing fungi. Effective prevention of ochratoxin A contamination therefore depends on good farming and agricultural practices. Good Agricultural Practices (GAP) including methods to reduce fungal infection and growth during harvest, storage, transport and processing provide the primary line of defense against contamination with ochratoxin A. To the best of our knowledge this is the first report of mycological assessment, especially the mycotoxins in pork byproducts in Egypt.

Keywords: Egyptian markets, mycotoxicosis, ochratoxin A, pork meat, pork by-products

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Authors: Sung-Hee Nam, Kwang-Gill Lee, You-Young Jo, HaeYong Kweon

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Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and From ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores. Yamanaka reported that although a complete fruiting body can be produced under optimal culture conditions, it should be regarded as synnemata because it does not develop into an ascoma bearing ascospores.

Keywords: paecilomyces tenuipes, entomopathogenic fungi, silkworm larva, bombyx mori

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Authors: Vipin Kumar Verma, Neeta Sehgal, Om Prakash

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Cyprinus carpio has a wide spread occurrence in the lakes and rivers of Europe and Asia. Heavy losses in natural environment due to anthropogenic activities, including pollution as well as pathogenic diseases have landed this fish in IUCN red list of vulnerable species. The significance of a suitable diet in preserving the health status of fish is widely recognized. In present study, artificial feed supplemented with leaves of two weed plants, Eichhornia crassipes and Ricinus communis were evaluated for their role on the fish immune system. To achieve this objective fish were acclimatized to laboratory conditions (25 ± 1 °C; 12 L: 12D) for 10 days prior to start of experiment and divided into 4 groups: non-challenged (negative control= A), challenged [positive control (B) and experimental (C & D)]. Group A, B were fed with non-supplemented feed while group C & D were fed with feed supplemented with 5% Eichhornia crassipes and 5% Ricinus communis respectively. Supplemented feeds were evaluated for their effect on growth, health, immune system and disease resistance in fish when challenged with Vibrio harveyi. Fingerlings of C. carpio (weight, 2.0±0.5 g) were exposed with fresh overnight culture of V. harveyi through bath immunization (concentration 2 Χ 105) for 2 hours on 10 days interval for 40 days. The growth was monitored through increase in their relative weight. The rate of mortality due to bacterial infection as well as due to effect of feed was recorded accordingly. Immune response of fish was analyzed through differential leucocyte count, percentage phagocytosis and phagocytic index. The effect of V. harveyi on fish organs were examined through histo-pathological examination of internal organs like spleen, liver and kidney. The change in the immune response was also observed through gene expression analysis. The antioxidant potential of plant extracts was measured through DPPH and FRAP assay and amount of total phenols and flavonoids were calculates through biochemical analysis. The chemical composition of plant’s methanol extracts was determined by GC-MS analysis, which showed presence of various secondary metabolites and other compounds. Investigation revealed immuno-modulatory effect of plants, when supplemented with the artificial feed of fish.

Keywords: immuno-modulation, gc-ms, Cyprinus carpio, Eichhornia crassipes, Ricinus communis

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Authors: Juan Peña Aguilar, Lilia Villasana, Rodrigo Valencia, Alberto Pastrana, Martin Vivanco, Juan Peña C

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Each year a growing number of companies entering Mexico in search of the domestic market share. These activities, including stores, telephone long distance and local raw materials and energy, and particularly the financial sector, have managed to significantly increase its weight in the flows of FDI in Mexico , however, you should consider whether these trends FDI are positive for the Mexican economy and these activities increase Mexican exports in the medium term , and its share in GDP , gross fixed capital formation and employment. In general stresses that these activities, by far, have been unable to significantly generate linkages with the rest of the economy, a process that has not favored with competitiveness policies and activities aimed at these neutral or horizontal. Since the nineties foreign direct investment (FDI) has shown a remarkable dynamism, both internationally and in Latin America and in Mexico. Only in Mexico the first recipient of FDI in importance in Latin America during 1990-1995 and was displaced by Brazil since FDI increased from levels below 1 % of GDP during the eighties to around 3 % of GDP during the nineties. Its impact has been significant not only from a macroeconomic perspective , it has also allowed the generation of a new industrial production structure and organization, parallel to a significant modernization of a segment of the economy. The case of Mexico also is particularly interesting and relevant because the destination of FDI until 1993 had focused on the purchase of state assets during privatization process. This paper aims to present FDI flows in Mexico and analyze the different business strategies that have been touched and encouraged by the FDI. On the one hand, looking briefly discuss regulatory issues and source and recipient of FDI sectors. Furthermore, the paper presents in more detail the impacts and changes that generated the FDI contribution of FDI in the Mexican economy , besides the macroeconomic context and later legislative changes that resulted in the current regulations is examined around FDI in Mexico, including aspects of the Free Trade Agreement (NAFTA). It is worth noting that foreign investment can not only be considered from the perspective of the receiving economic units. Instead, these flows also reflect the strategic interests of transnational corporations (TNCs) and other companies seeking access to markets and increased competitiveness of their production networks and global distribution, among other reasons. Similarly it is important to note that foreign investment in its various forms is critically dependent on historical and temporal aspects. Thus, the same functionality can vary significantly depending on the specific characteristics of both receptor units as sources of FDI, including macroeconomic, institutional, industrial organization, and social aspects, among others.

Keywords: foreign direct investment (FDI), competitiveness, neoliberal regime, globalization, gross domestic product (GDP), NAFTA, macroeconomic

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Authors: A. Zuchowska, A. Buta, M. Mazurkiewicz-Pawlicka, A. Malolepszy, L. Stobinski, Z. Brzozka

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In recent years, graphene-based materials are finding more and more applications in biological science. As a thin, tough, transparent and chemically resistant materials, they appear to be a very good material for the production of implants and biosensors. Interest in graphene derivatives also resulted at the beginning of research about the possibility of their application in cancer therapy. Currently, the analysis of their potential use in photothermal therapy and as a drug carrier is mostly performed. Moreover, the direct anticancer properties of graphene-based materials are also tested. Nowadays, cytotoxic studies are conducted on in vitro cell culture in standard culture vessels (macroscale). However, in this type of cell culture, the cells grow on the synthetic surface in static conditions. For this reason, cell culture in macroscale does not reflect in vivo environment. The microfluidic systems, called Lab-on-a-chip, are proposed as a solution for improvement of cytotoxicity analysis of new compounds. Here, we present the evaluation of cytotoxic properties of graphene oxide (GO) on breast, liver and colon cancer cell line in a microfluidic system in two spatial models (2D and 3D). Before cell introduction, the microchambers surface was modified by the fibronectin (2D, monolayer) and poly(vinyl alcohol) (3D, spheroids) covering. After spheroid creation (3D) and cell attachment (2D, monolayer) the selected concentration of GO was introduced into microsystems. Then monolayer and spheroids viability/proliferation using alamarBlue® assay and standard microplate reader was checked for three days. Moreover, in every day of the culture, the morphological changes of cells were determined using microscopic analysis. Additionally, on the last day of the culture differential staining using Calcein AM and Propidium iodide were performed. We were able to note that the GO has an influence on all tested cell line viability in both monolayer and spheroid arrangement. We showed that GO caused higher viability/proliferation decrease for spheroids than a monolayer (this was observed for all tested cell lines). Higher cytotoxicity of GO on spheroid culture can be caused by different geometry of the microchambers for 2D and 3D cell cultures. Probably, GO was removed from the flat microchambers for 2D culture. Those results were also confirmed by differential staining. Comparing our results with the studies conducted in the macroscale, we also proved that the cytotoxic properties of GO are changed depending on the cell culture conditions (static/ flow).

Keywords: cytotoxicity, graphene oxide, monolayer, spheroid

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Authors: Aidin Foroutan, David S. Wishart, Leluo L. Guan, Carolyn Fitzsimmons

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Maximizing efficiency and growth potential of beef cattle requires not only genetic selection (i.e. residual feed intake (RFI)) but also adequate nutrition throughout all stages of growth and development. Nutrient restriction during gestation has been shown to negatively affect post-natal growth and development as well as fertility of the offspring. This, when combined with RFI may affect progeny traits. This study aims to investigate the impact of selection for divergent genetic potential for RFI and maternal nutrition during early- to mid-gestation, on bull calf traits such as fertility and muscle development using multiple ‘omics’ approaches. Comparisons were made between High-diet vs. Low-diet and between High-RFI vs. Low-RFI animals. An epigenetics experiment on semen samples identified 891 biomarkers associated with growth and development. A gene expression study on Longissimus thoracis muscle, semimembranosus muscle, liver, and testis identified 4 genes associated with muscle development and immunity of which Myocyte enhancer factor 2A [MEF2A; induces myogenesis and control muscle differentiation] was the only differentially expressed gene identified in all four tissues. An initial metabolomics experiment on serum samples using nuclear magnetic resonance (NMR) identified 4 metabolite biomarkers related to energy and protein metabolism. Once all the biomarkers are identified, bioinformatics approaches will be used to create a database covering all the ‘omics’ data collected from this project. This database will be broadened by adding other information obtained from relevant literature reviews. Association analyses with these data sets will be performed to reveal key biological pathways affected by RFI and maternal nutrition. Through these association studies between the genome and metabolome, it is expected that candidate biomarker genes and metabolites for feed efficiency, fertility, and/or muscle development are identified. If these gene/metabolite biomarkers are validated in a larger animal population, they could potentially be used in breeding programs to select superior animals. It is also expected that this work will lead to the development of an online tool that could be used to predict future traits of interest in an animal given its measurable ‘omics’ traits.

Keywords: biomarker, maternal nutrition, omics, residual feed intake

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Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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Authors: Xiaoyuan Chen

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Background: This study aimed to characterize the epidemiological and clinical features of five rare subtypes of hepatocellular carcinoma (HCC) and to create a competing risk nomogram for predicting cancer-specific survival. Methods: This study used the Surveillance, Epidemiology, and End Results database to analyze the clinicopathological data of 50,218 patients with classic HCC and five rare subtypes (ICD-O-3 Histology Code=8170/3-8175/3) between 2004 and 2018. The annual percent change (APC) was calculated using Joinpoint regression, and a nomogram was developed based on multivariable competing risk survival analyses. The prognostic performance of the nomogram was evaluated using the Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve. Decision curve analysis was used to assess the clinical value of the models. Results: The incidence of scirrhous carcinoma showed a decreasing trend (APC=-6.8%, P=0.025), while the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality plateau in all subtypes during the period. Clear cell carcinoma was the most common subtype (n=551, 1.1%), followed by fibrolamellar (n=241, 0.5%), scirrhous (n=82, 0.2%), spindle cell (n=61, 0.1%), and pleomorphic (n=17, ~0%) carcinomas. Patients with fibrolamellar carcinoma were younger and more likely to have non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro clinical characteristics and outcomes as classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were identified as independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice. Conclusion: The rare subtypes of HCC had distinct clinicopathological features and biological behaviors compared with classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could accurately predict prognoses, which is beneficial for individualized management.

Keywords: hepatocellular carcinoma, pathological subtype, fibrolamellar carcinoma, scirrhous carcinoma, clear cell carcinoma, spindle cell carcinoma, pleomorphic carcinoma

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Authors: Bimali Sanjeevani Weerakoon, Toshiaki Osuga, Takehisa Konishi

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Magnetic Resonance Imaging Contrast Agents (MRI-CM) are significant in the clinical and biological imaging as they have the ability to alter the normal tissue contrast, thereby affecting the signal intensity to enhance the visibility and detectability of images. Superparamagnetic Iron Oxide (SPIO) nanoparticles, coated with dextran or carboxydextran are currently available for clinical MR imaging of the liver. Most SPIO contrast agents are T2 shortening agents and Resovist (Ferucarbotran) is one of a clinically tested, organ-specific, SPIO agent which has a low molecular carboxydextran coating. The enhancement effect of Resovist depends on its relaxivity which in turn depends on factors like magnetic field strength, concentrations, nanoparticle properties, pH and temperature. Therefore, this study was conducted to investigate the impact of field strength and different contrast concentrations on enhancement effects of Resovist. The study explored the MRI signal intensity of Resovist in the physiological range of plasma from T2-weighted spin echo sequence at three magnetic field strengths: 0.47 T (r1=15, r2=101), 1.5 T (r1=7.4, r2=95), and 3 T (r1=3.3, r2=160) and the range of contrast concentrations by a mathematical simulation. Relaxivities of r1 and r2 (L mmol-1 Sec-1) were obtained from a previous study and the selected concentrations were 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2.0, and 3.0 mmol/L. T2-weighted images were simulated using TR/TE ratio as 2000 ms /100 ms. According to the reference literature, with increasing magnetic field strengths, the r1 relaxivity tends to decrease while the r2 did not show any systematic relationship with the selected field strengths. In parallel, this study results revealed that the signal intensity of Resovist at lower concentrations tends to increase than the higher concentrations. The highest reported signal intensity was observed in the low field strength of 0.47 T. The maximum signal intensities for 0.47 T, 1.5 T and 3 T were found at the concentration levels of 0.05, 0.06 and 0.05 mmol/L, respectively. Furthermore, it was revealed that, the concentrations higher than the above, the signal intensity was decreased exponentially. An inverse relationship can be found between the field strength and T2 relaxation time, whereas, the field strength was increased, T2 relaxation time was decreased accordingly. However, resulted T2 relaxation time was not significantly different between 0.47 T and 1.5 T in this study. Moreover, a linear correlation of transverse relaxation rates (1/T2, s–1) with the concentrations of Resovist can be observed. According to these results, it can conclude that the concentration of SPIO nanoparticle contrast agents and the field strengths of MRI are two important parameters which can affect the signal intensity of T2-weighted SE sequence. Therefore, when MR imaging those two parameters should be considered prudently.

Keywords: Concentration, resovist, field strength, relaxivity, signal intensity

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Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

Abstract:

Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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Authors: M. Younus, Muhammad Shafique, M. Athar Khan, Tanveer Akhtar , M. Moeen Athar

Abstract:

A total of 48 apparently healthy weaned sheep lambs (Ovis aries) of 8-10 weeks old weighing 7-10 Kg were purchased from the contractors, maintained in the experimental station of University of the Punjab, Quaid-e-Azam Campus at Lahore, Pakistan. They were dewormed against nematodes with levamisole (ICI) at recommended dose rates. The feces were tested against the parasitic eggs, no helminths ova were seen. All the 48 sheep lambs were divided into two groups i.e. group A & group B. Group 'A' comprising of 40 sheep, kept as infected groups whereas group 'B' comprising of 08 sheep & kept as a new infected control group. Each sheep lamb of group A was given 3-4 fresh gravid segments contains 2-3 thousand eggs of Echinococcus granulosus. These were collected from experimentally infected dogs by feeding fresh hydrated cysts collected from liver & lungs of sheep after slaughtering. Each lamb was fed with fresh gravid segments for a total period of 5 days or each alternate day. Coagulated blood was collected before the start of infected diet and after every month by jugular phlebotomy of each sheep lamb from the infected & new infected control group. One lamb each from group A & group B was slaughtered at the end of each month for the presence of macroscopic hydatid cyst in viscera & abdominal cavity. After 180 days of the experiment, hydatid cysts were confirmed in the abdominal cavity. Hematological parameters of zero days & then at the end of every month revealed that there was a gradual increase (PL 0.05) in the White Blood Cell (WBC), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC) and Erythrocyte Sedimentation Rates (ESR). The increasing trend was probably due to inflammatory response and lytic effect of the newly developing E. granulosus hydatid cysts. The red blood cell (RBC), Hemoglobin (HB), Packed Cell Volume (PCV) and Mean Corpuscular Hemoglobin (MCH) infected groups were decreased significantly as compared to the control group (PL 0.05). The experiment was terminated at the end of the 7th month. It can be concluded that Echinococcus granulosus can damage livestock and other intermediate hosts such as horses, the development of hydatid cysts affect the organs due to the growing cysts pressuring the organ tissues. Parts of the tissue die, which impairs the functioning of the affected organ. The clinical signs depend on the affected organ. The major damage for livestock is organ condemnation at slaughter.

Keywords: echinococcus granulosus, hydatidosis, sheep, hematology

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Authors: Tzu-Ting Hu, Jung-Der Wang, Ming-Yeng Lin, Jin-Luh Chen, Perng-Jy Tsai

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The vinyl chloride monomer (VCM) has been classified as group 1 (human) carcinogen by the IARC. Workers exposed to VCM are known associated with the development of the liver cancer and hence might cause economical and health losses. Particularly, for those work for the petrochemical industry have been seriously concerned in the environmental and occupational health field. Considering assessing workers’ health risks and their resultant economical and health losses requires the establishment of long-term VCM exposure data for any similar exposure group (SEG) of interest, the development of suitable technologies has become an urgent and important issue. In the present study, VCM exposures for petrochemical industry workers were determined firstly based on the database of the 'Workplace Environmental Monitoring Information Systems (WEMIS)' provided by Taiwan OSHA. Considering the existence of miss data, the reconstruction of historical exposure techniques were then used for completing the long-term exposure data for SEGs with routine operations. For SEGs with non-routine operations, exposure modeling techniques, together with their time/activity records, were adopted for determining their long-term exposure concentrations. The Bayesian decision analysis (BDA) was adopted for conducting exposure and health risk assessments for any given SEG in the petrochemical industry. The resultant excessive cancer risk was then used to determine the corresponding loss of quality-adjusted life expectancy (QALE). Results show that low average concentrations can be found for SEGs with routine operations (e.g., VCM rectification 0.0973 ppm, polymerization 0.306 ppm, reaction tank 0.33 ppm, VCM recovery 1.4 ppm, control room 0.14 ppm, VCM storage tanks 0.095 ppm and wastewater treatment 0.390 ppm), and the above values were much lower than that of the permissible exposure limit (PEL; 3 ppm) of VCM promulgated in Taiwan. For non-routine workers, though their high exposure concentrations, their low exposure time and frequencies result in low corresponding health risks. Through the consideration of exposure assessment results, health risk assessment results, and QALE results simultaneously, it is concluded that the proposed method was useful for prioritizing SEGs for conducting exposure abatement measurements. Particularly, the obtained QALE results further indicate the importance of reducing workers’ VCM exposures, though their exposures were low as in comparison with the PEL and the acceptable health risk.

Keywords: exposure assessment, health risk assessment, petrochemical industry, quality-adjusted life years, vinyl chloride monomer

Procedia PDF Downloads 193

Authors: Ruslin, R. E. Kartasasmita, M. S. Wibowo, S. Ibrahim

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An aphrodisiac is a substance contained in food or drug that can arouse sexual instinct and increase pleasure while working, these substances derived from plants, animals, and minerals. When consuming substances that have aphrodisiac activity and duration can improve the sexual instinct. The natural aphrodisiac effect can be obtained through plants, animals, and minerals. Leonurine compound has aphrodisiac activity, these compounds can be isolated from plants of Leonurus Sp, Sundanese people is known as deundereman, this plant is empirical has aphrodisiac activity and based on the isolation of active compounds from plants known to contain compounds leonurine, so that the compound is expected to have activity aphrodisiac. Leonurine compound can be isolated from plants or synthesized chemically with material dasa siringat acid. Leonurine compound can be obtained commercial and derivatives of these compounds can be synthesized in an effort to increase its activity. This study aims to obtain derivatives leonurine better aphrodisiac activity compared with the parent compound, modified the structure of the compounds in the form leonurin guanidino butyl ester group with butyl amin and bromoetanol. ArgusLab program version 4.0.1 is used to determine the binding energy, hydrogen bonds and amino acids involved in the interaction of the compound PDE5 receptor. The in vivo test leonurine compounds and derivatives as an aphrodisiac ingredients and hormone testosterone levels using 27 male rats Wistar strain and 9 female mice of the same species, ages ranged from 12 weeks rats weighing + 200 g / tail. The test animal is divided into 9 groups according to the type of compounds and the dose given. Each treatment group was orally administered 2 ml per day for 5 days. On the sixth day was observed male rat sexual behavior and taking blood from the heart to measure testosterone levels using ELISA technique. Statistical analysis was performed in this study is the ANOVA test Least Square Differences (LSD) using the program Statistical Product and Service Solutions (SPSS). Aphrodisiac efficacy of the leonurine compound and its derivatives have proven in silico and in vivo test, the in silico testing leonurine derivatives have smaller binding energy derivatives leonurine so that activity better than leonurine compounds. Testing in vivo using rats of wistar strain that better leonurine derivative of this compound shows leonurine that in silico studies in parallel with in vivo tests. Modification of the structure in the form of guanidine butyl ester group with butyl amin and bromoethanol increase compared leonurine compound for aphrodisiac activity, testosterone derivatives of compounds leonurine experienced a significant improvement especial is 1RD compounds especially at doses of 100 and 150 mg/bb. The results showed that the compound leonurine and its compounds contain aphrodisiac activity and increase the amount of testosterone in the blood. The compound test used in this study acts as a steroid precursor resulting in increased testosterone.

Keywords: aphrodisiac dysfunction erectile leonurine 1-RD 2-RD, dysfunction, erectile leonurine, 1-RD 2-RD

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Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

Abstract:

Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

Procedia PDF Downloads 99

Authors: Nelson R. Osungbemiro, O. A. Bello-Olusoji, M. Oladipupo

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This study was carried out to determine the effects of probiotics Pseudomonas fluorescens on the growth performance, histology examination and immune modulation of African Catfish, (Clarias gariepinus) challenged with Clostridium botulinum. P. fluorescens, and C. botulinum isolates were removed from the gut, gill and skin organs of procured adult samples of Clarias gariepinus from commercial fish farms in Akure, Ondo State, Nigeria. The physical and biochemical tests were performed on the bacterial isolates using standard microbiological techniques for their identification. Antibacterial activity tests on P. fluorescens showed inhibition zone with mean value of 3.7 mm which indicates high level of antagonism. The experimental diets were prepared at different probiotics bacterial concentration comprises of five treatments of different bacterial suspension, including the control (T1), T2 (10³), T3 (10⁵), T4 (10⁷) and T5 (10⁹). Three replicates for each treatment type were prepared. Growth performance and nutrients utilization indices were calculated. The proximate analysis of fish carcass and experimental diet was carried out using standard methods. After feeding for 70 days, haematological values and histological test were done following standard methods; also a subgroup from each experimental treatment was challenged by inoculating Intraperitonieally (I/P) with different concentration of pathogenic C. botulinum. Statistically, there were significant differences (P < 0.05) in the growth performance and nutrient utilization of C. gariepinus. Best weight gain and feed conversion ratio were recorded in fish fed T4 (10⁷) and poorest value obtained in the control. Haematological analyses of C. gariepinus fed the experimental diets indicated that all the fish fed diets with P. fluorescens had marked significantly (p < 0.05) higher White Blood Cell than the control diet. The results of the challenge test showed that fish fed the control diet had the highest mortality rate. Histological examination of the gill, intestine, and liver of fish in this study showed several histopathological alterations in fish fed the control diets compared with those fed the P. fluorescens diets. The study indicated that the optimum level of P. fluorescens required for C. gariepinus growth and white blood cells formation is 10⁷ CFU g⁻¹, while carcass protein deposition required 10⁵ CFU g⁻¹ of P. fluorescens concentration. The study also confirmed P. fluorescens as efficient probiotics that is capable of improving the immune response of C. gariepinus against the attack of a virulent fish pathogen, C. botulinum.

Keywords: Clarias gariepinus, Clostridium botulinum, probiotics, Pseudomonas fluorescens

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Authors: Norihiro Kato, Yuriko Takayama

Abstract:

Some gram-negative bacteria enable the simultaneous activation of gene expression involved in N-acylhomoserine lactone (AHL) dependent cell-to-cell communication system. Such regulatory system for the bacterial group behavior is termed as quorum sensing (QS) because a diffusible AHL signal can accumulate around the cell during the increase of the cell density and trigger activation of the sequential QS process. By blocking the QS, the expression of diverse genes related to infection, antibiotic production, and biofilm formation is inhibited. Conditioning of QS by regulation of the DNA-receptor-AHL interaction is a potential target for enhancing host defenses against pathogenicity. We focused on engineered application of transcriptional regulator SpnR produced in opportunistic human pathogen Serratia marcescens. The SpnR can interact with AHL signals at an N-terminal domain and also with a promoter region of a QS target gene at a C-terminal domain. As the initial process of the QS activation, the SpnR forms a complex with the AHL to enhance the expression of pig cluster; the SpnR normally acts as an activator for the expression of the QS-dependent gene. In this research, we attempt to artificially control QS by changing the role of SpnR. The QS-dependent prodigiosin production is expected to inhibit by externally added SpnR in the culture broth of AS-1 strain because the AHL concentration was kept below the threshold by AHL-SpnR complex formation. Maltose-binding protein (MBP)-tagged SpnR (MBP-SpnR) was overexpressed in Escherichia coli and purified using an affinity chromatography equipped with an amylose resin column. The specific interaction between AHL and MBP-SpnR was demonstrated by quartz crystal microbalance (QCM) sensor. AHL with amino end-group was coupled with COOH-terminated self-assembled monolayer prepared on a gold electrode of 27-MHz quartz crystal sensor using water-soluble carbodiimide. After the injection of MBP-SpnR into a cup-type sensor cell filled with the buffer solution, time course of resonant frequency change (ΔFs) was determined. A decrease of ΔFs clearly showed the uptake of MBP-SpnR onto the AHL-immobilized electrode. Furthermore, no binding affinity was observed after the heat-inactivation of MBP-SpnR at 80ºC. These results suggest that MBP-SpnR possesses a specific affinity for AHL. MBP-SpnR was added to the culture medium as an AHL trap to study inhibitory effects on intracellularly accumulated prodigiosin. With approximately 2 µM MBP-SpnR, the amount of prodigiosin induced was half that of the control without any additives. In conclusion, the function of SpnR could be switched by adding it to the cell culture. Exogenously added MBP-SpnR possesses high affinity for AHL derived from cells and acts as an inhibitor of AHL-mediated QS.

Keywords: intracellular signaling, microbial biotechnology, quorum sensing, transcriptional regulator

Procedia PDF Downloads 261

Authors: E. Isaac, I. Jalo, Y. Alkali, A. Ajani, A. Rasaki, Y. Jibrin, K. Mustapha, A. Ayuba, S. Charanchi, H. Danlami

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Introduction: Hepatitis B infection continues to be a serious global health problem with about 2 billion people infected worldwide, many of these in sub-Saharan Africa. Nigeria is one of the countries with the highest incidence, with a prevalence of 10-15%. Methods: Records of Hepatitis B surface and envelope antigen test results in adults in Federal Teaching Hospital, Gombe between May 2000 and May 2015 were retrieved and analyzed. Findings: Adult out-patient consultations and in-patient admissions were 343,083 and 67,761 respectively, accounting for 87% of total. Hepatitis B surface antigenaemia was tested for in 23,888 adults and children. 88.9% (21240) were adults. Males constituted 56% (11902/21240) and females 44% (9211/21240). 5104 (24.0%) of tested individuals were 19-25years; 12,039 (56.7%) 26-45years; 21119 (9.0%) 46-55years; 2.8% (590/21240) and 766 (3.6%) >65years. Among adult males, 17% (2133/11902) was contributed by ages 19-25. 58% (7017/11902), 11.9% (1421/11902), 6.4% (765/11902) and 4.7% (563/11902) of males were 26-45 years old, 46-55 years old and 56-65 years and >65year old respectively. Adults aged 19-25years, 26-45 years, 46-55years, 56-65 and > 65years each constituted 32% (2966/9211); 54.4% (5009/9211); 7.4% (684/9211), 3.8% (350/9211) and 2.2% (201/9211) of females respectively. 16.2% (3431/21,240) demonstrated Hepatitis B surface antigenaemia. The sero-positivity rate was 16.9% (865//5104) between 19-25years, 21.2% (2559/12,039) among 26-45year old individuals. 17.9% (377/2111); 14.1% (83/590) and 7.3% (56/766) of 46-55year old, 56-65year old and >65year old individuals screened were seropositive. The highest sero-positivity rate was found in male young adults aged 19-25years 27.9% (398/1426) and lowest in elderly males 7.4% (28/377). HBe antigen testing rate among HbSAg seropositive individuals was 97.3% (3338/3431). Males constituted 59.7% (1992/3338) and females 40.3% (1345/3338). 25.3% (844/3338) were aged 19-25years; 61.1% (2039/3338) 26-45years; 10.2% (340/3338) 46-55years; 2.7% (90/3338) 56-65years and 0.7% >65years old. HB e antigenaemia was positive in 8.2% (275/3338) of those tested. 41% (113/275); 50.2% (138/275); 5.4% (15/275); 1.8% (5/275) and 1.1 (3/275) of HB e sero-positivity was among age groups 19-25, 26-45, 46-55, 56-65 and > 65year old individuals. Dual sero-positivity rate was highest 13% (113/844) in young adults 19-25years and lowest between 46-55years; 15/340 (4.4%). 4.2% (15/360); 13.5% (69/512); 6.7% (90/1348); 4.6% (10/214); 5% (2/40) and 6.7% (1/15) of males aged 19-25; 26-45; 46-55; 56-65; and >65years had HB e antigenaemia respectively. Among females - 27/293 (9.2%) aged 19-25; 26/500 (5.2%) 26-45; 2/84 (2.4%) 46-55; 1/12 (8.3%) 56-65 and 1/9(11.1%) >65years had dual antigenaemia. In women of childbearing age, 6.9% (53/793) had a dual carriage. Conclusion: Dual hepatitis B surface and envelope antigenaemia are highest in young adult males. This will have significant implications for the development of chronic liver disease and hepatocellular carcinoma.

Keywords: adult, Hepatitis B, Nigeria, dual carriage

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Yuriko Takayama, Norihiro Kato

Abstract:

Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

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Authors: Abhit Kumar

Abstract:

The world is full of master slave Telemanipulator where the doctor’s masters the console and the surgical arm perform the operations, i.e. these robots are passive robots, what the world needs to focus is that in use of these passive robots we are acquiring doctors for operating these console hence the utilization of the concept of robotics is still not fully utilized ,hence the focus should be on active robots, Auto Surgical-Emissive Hand use the similar concept of active robotics where this anthropomorphic hand focuses on the autonomous surgical, emissive and scanning operation, enabled with the vision of 3 way emission of Laser Beam/-5°C < ICY Steam < 5°C/ TIC embedded in palm of the anthropomorphic hand and structured in a form of 3 way disc. Fingers of AS-EH (Auto Surgical-Emissive Hand) as called, will have tactile, force, pressure sensor rooted to it so that the mechanical mechanism of force, pressure and physical presence on the external subject can be maintained, conversely our main focus is on the concept of “emission” the question arises how all the 3 non related methods will work together that to merged in a single programmed hand, all the 3 methods will be utilized according to the need of the external subject, the laser if considered will be emitted via a pin sized outlet, this radiation is channelized via a thin channel which further connect to the palm of the surgical hand internally leading to the pin sized outlet, here the laser is used to emit radiation enough to cut open the skin for removal of metal scrap or any other foreign material while the patient is in under anesthesia, keeping the complexity of the operation very low, at the same time the TIC fitted with accurate temperature compensator will be providing us the real time feed of the surgery in the form of heat image, this gives us the chance to analyze the level, also ATC will help us to determine the elevated body temperature while the operation is being proceeded, the thermal imaging camera in rooted internally in the AS-EH while also being connected to the real time software externally to provide us live feedback. The ICY steam will provide the cooling effect before and after the operation, however for more utilization of this concept we can understand the working of simple procedure in which If a finger remain in icy water for a long time it freezes the blood flow stops and the portion become numb and isolated hence even if you try to pinch it will not provide any sensation as the nerve impulse did not coordinated with the brain hence sensory receptor did not got active which means no sense of touch was observed utilizing the same concept we can use the icy stem to be emitted via a pin sized hole on the area of concern ,temperature below 273K which will frost the area after which operation can be done, this steam can also be use to desensitized the pain while the operation in under process. The mathematical calculation, algorithm, programming of working and movement of this hand will be installed in the system prior to the procedure, since this AS-EH is a programmable hand it comes with the limitation hence this AS-EH robot will perform surgical process of low complexity only.

Keywords: active robots, algorithm, emission, icy steam, TIC, laser

Procedia PDF Downloads 354

Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

Abstract:

Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

Procedia PDF Downloads 128

Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

Abstract:

Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

Procedia PDF Downloads 91